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RHDV2 overcoming RHDV immunity in wild rabbits (Oryctolagus cuniculus) in Australia
Abstract
The emergence of rabbit haemorrhagic disease virus 2 (RHDV2) in Europe (Le Gall-Reculé and others 2011) has been associated with declines in wild rabbit (Oryctolagus cuniculus) populations (Delibes-Mateos and others 2014; Guerrero-Casado and others 2016; Monterroso and others 2016) previously exposed to RHDV. All RHDV genotypes of the G1-G6 genogroups, hereafter referred to as RHDV, belong to the same antigenic serotype (Le Gall-Reculé and others 2013). The unique antigenic nature of RHDV2 (Le Gall-Reculé and others 2013; Bárcena and others 2015) is reflected in its capacity to kill rabbits vaccinated against RHDV (Le Gall-Reculé and others 2011; Dalton and others 2014; McGowan and Choudhury 2016) and its rapid spread in Europe (Dalton and others 2012; Abrantes and others 2013; Le Gall-Reculé and others 2013; Baily and others 2014; Westcott and others 2014) and Australia (Hall and others 2015) with associated peaks in RHD epizootics. The capacity of RHDV2 to overcome RHDV-immunity, reported so far only in vaccinated rabbits, may partly explain the observed decline in wild rabbit populations where RHDV had already been circulating. Here we report the infection by RHDV2 of three Australian wild rabbits with a known RHDV antibody-positive serological history, with clinical signs of RHD visible in one fresh carcass, the first documented cases of RHDV-immune wild rabbits being infected with and/or succumbing to RHDV2 infection. This demonstrated capacity of RHDV2 to overcome immunity derived from natural infections with RHDV supports an immunogenic difference between RHDV and RHDV2 at the level of serotype.
... In particular, under laboratory experimental conditions, the reported mortality rate for RHDV was 70%-90% and 5%-70% for RHDV2 (Lavazza & Capucci, 2018). However, RHDV2 can overcome immunity in wild rabbits previously infected by RHDV (Peacock et al., 2017). Another major difference between these two virus variants is that rabbits younger than 8 weeks of age are highly resistant to disease caused by RHDV (Abrantes et al., 2012;Morisse et al., 1991;Xu & Chen, 1989), while RHDV2 is responsible for mortalities in young animals from the age of 11 days (Calvete et al., 2018;Dalton et al., 2012Dalton et al., , 2014Lavazza & Capucci, 2018;Le Gall-Reculé et al., 2013;Müller et al., 2021;Neave et al., 2018). ...
... Several hypotheses may explain this epidemiology. By providing some transient immunity, RHDV immunity caused by RHDV vaccination in our case or by previous exposure to RHDV in wild populations (Abrantes et al., 2012;Cooke, 2002;Müller et al., 2021;Peacock et al., 2017) may have lengthened the progress of RHDV2 outbreaks. However, in the absence of RHDV vaccine immunity in the population, the RHDV2 outbreak could have been more intense and rapid, as reported by Jiménez-Ruiz et al. (2023), but ultimately with a comparable overall demographic impact. ...
... Nevertheless, low or transient vaccine effectiveness is also likely when faced with a variant of the virus. And, despite rabbits immunized against RHDV possibly dying from a subsequent RHDV2 infection (Peacock et al., 2017), it was already known that vaccination against RHDV could confer some transient protection against RHDV2 (Dalton et al., 2014;Le Gall-Reculé et al., 2011;Müller et al., 2021). Thus, the short-term benefit of RHDV vaccination on survival that we observed supports the hypothesis of an RHDV2 outbreak causing the population decline. ...
Infectious diseases can cause considerable mortality in vertebrate populations, especially when a new pathogen emerges. Quantifying the impact of diseases on wild populations and dissecting the underlying mechanisms requires longitudinal individual monitoring combining demographic and epidemiologic data. Such longitudinal population studies are rare. Rabbit hemorrhagic disease (RHD) is one of the main causes of the decline in European wild rabbit (Oryctolagus cuniculus) populations. A new genotype of RHD virus (RHDV), called RHDV2 or GI.2, emerged in 2010, posing a new threat to previously weakened populations, particularly as this virus can infect individuals already immune to classical RHDV strains. Taking advantage of intensive monitoring from 2009 to 2014 by physical captures and microchip detections of a semi‐captive population of rabbits, we finely assessed the demographic impact of an initial RHDV2 outbreak that occurred in the population and identified the most affected demographic parameters. A multi‐event modeling analysis revealed decreased survival in both juveniles and adults in 2011 and 2012, suggesting an RHDV2 outbreak for two consecutive years. The short‐term survival benefit of vaccination against classical RHDV strains only during these years, and the recovery of carcasses with RHDV2 detection, supported this hypothesis. Variations in population vaccination coverage also explain the difference in adult survival between the two years of the outbreak. And the transient protective effect of vaccination could explain the prolonged duration of the outbreak. A brief episode of myxomatosis in 2011 seems to have had only a limited impact on the population. During outbreak years, in individuals not recently vaccinated, monthly juvenile survival crashed (0.55), and annual adult survival was three times lower than in normal years (0.21 vs. 0.69). The combination of successive juvenile and adult survival estimates for unvaccinated rabbits during the outbreak years resulted in a very low recruitment rate in the breeding population. Finally, RHDV2 outbreaks appear to have caused mortalities comparable to those caused by older classical RHDV strains and may have a strong demographic impact on wild populations of European rabbit. This work highlights the importance of long‐term observational and experimental studies to better understand the impact of epidemics on animal populations.
... Rabbit population monitoring using vehicle-based spotlight transect counts began at IFRNP in February 1992 and the current 23.7 km transects had been counted quarterly in most years since 2002, 29 but with no counts in 2015 and one or two missing counts in three other recent years. RHDV2 was identified from liver or bone marrow of carcases collected at monitoring sites using PCR and genetic sequencing (details in ref 33 ). ...
... RHDV2 was detected at several sites within 15 km of Turretfield in February, March and April 2016, then at Turretfield on May 4, 2016. 33 A myxomatosis epizootic had passed through the population in March and April but none of the four carcases collected at Turretfield during that period contained RHDV or RHDV2. Nevertheless, trapping data from April 2016 were excluded from these analyses because RHDV2 may have been present but undetected. ...
... We cannot be certain that the population declines are entirely attributable to RHDV2, even though it has largely displaced earlier GI.1 RHDV variants in Australia 35 and caused high mortality in rabbits that were immune to those earlier variants. 33 Recently emerged, virulent myxoma viruses 36 appear to have contributed to the decline at Turretfield in April 2016. Synergistic effects between the two diseases may also be important if population-level susceptibility to myxomatosis increased due to RHDV2-induced mortality in old rabbits which were immune to both GI.1 RHDV and myxomatosis. ...
Lagovirus europaeus
GI.2, also commonly known as rabbit haemorrhagic disease virus 2, was first detected at two long-term monitoring sites for European rabbits,Oryctolagus cuniculus, in South Australia, in mid-2016. Numbers of rabbits in the following 12-18 months were reduced to approximately 20 per cent of average numbers in the preceding 10 years. The impact recorded at the two South Australian sites, if widespread in Australia and persistent for several years, is likely to be of enormous economic and environmental benefit.
... The first rabbits on the site confirmed to have RHDV2 were in 2016 and our serological data gave evidence that RHDV2 could overcome antibodies to RHDV1 [59]. Since then, the population has continued to decline with RHDV2 remaining as the dominant virus [51]. ...
... The fly traps are cheap, reusable and durable-our traps remained serviceable after three years of continuous use. However, manual carcass searches remain relevant for use during smallerscale intensive studies of outbreak epidemiology (such as [50,59]) where demographic details of rabbit mortality are required. ...
Surveillance of wildlife virus impacts can be passive or active. Both approaches have their strengths and weaknesses, especially regarding cost and knowledge that can be gained. Monitoring of rabbit haemorrhagic disease virus (GI.1 and GI.2) in South Australia has utilised both strategies and their methods and gained insights are discussed. Active strategies to monitor the continuing impact of rabbit haemorrhagic disease virus 2 (GI.2) on susceptible lagomorphs in countries such as the USA, Mexico, South Africa, Spain, France and Portugal are encouraged to gain critical insights into the evolution, spread and impact of this virus. Furthermore, there are lessons here for the international monitoring of diseases in wildlife, particularly where there is a risk of them becoming zoonotic.
... The observation of partial protection between GI.1 and GI.2 was supported by data from RHDV GI.2 infections in Australia where mortality was detected in RHDV domestic vaccinated animals [100] and contributed to its rapid spread in the wild [101]. Currently, it appears as though RHDV GI.2 has become the predominant RHDV on the Iberian Peninsula [102,103], and also on mainland Australia replacing endemic strains of RHDV GI.1 [100]. ...
... The marked antigenic differences observed between RHDV GI.1 and RHDV GI.2 [168], explain the lack of efficient protection against RHDV GI.2 afforded by RHDV GI.1 inactivated vaccines [91,92], as well as, the capacity of RHDV GI.2 to overcome immunity derived from natural infections with RHDV GI.1 [101]. Since the emergence of RHDV GI.2 the development of diagnostic tools has been a very important issue and different techniques and methodologies have been improved for specific detection of RHDV GI.2 [168,[175][176][177]. ...
Our understanding of molecular biology of the viruses that infect lagomorphs is largely limited to the leporipoxvirus myxoma virus (MYXV) and the lagoviruses rabbit haemorrhagic disease virus (RHDV) and European brown hare syndrome virus (EBHSV) that infect the European rabbit (Oryctolagus cuniculus) and the European brown hare (Lepus europaeus) respectively. Thanks to the great effort of historic surveillance studies and careful sample archiving, the molecular evolution of these viruses is being resolved. Although historically considered viruses that cause species specific diseases recent reports show that several lagomorphs may now face the threat of these maladies. The driving factors behind these changes has not been determined and the effect of these species jumps on lagomorph populations has yet to be seen. Lagomorphs are also affected by several other lesser studied viral diseases. In addition, recent metagenomic studies have led to the identification of novel lagomorph viruses the importance of these to lagomorph health remains to be fully determined. In this chapter we summarize molecular aspects of viruses that infect lagomorphs, paying particular attention to recent interspecies infections.
... RHDV2 can cause the death of young rabbits aged 2-3 weeks, which suggests that RHDV2 may use different receptors (Le Gall-Recule et al., 2011). RHDV2 has now been reported in many countries in Europe, Australia, Africa, and North America (Abrantes et al., 2013;Camarda et al., 2014;Dalton et al., 2014Dalton et al., , 2012Duarte et al., 2015;Hall et al., 2015;Le Gall-Recule et al., 2011;Martin-Alonso et al., 2016;Neimanis et al., 2018b;Rouco et al., 2019;Westcott et al., 2014), and in many areas, RHDV2 has replaced classic RHDV as the major cause of RHD (Lopes et al., 2014;Mahar et al., 2018;Peacock et al., 2017).Most strikingly, RHDV2 can cause the death of classic RHDV-vaccinated rabbits (Peacock et al., 2017), which suggests that RHDV2 differs antigenically from classic RHDV. Therefore, an RHDV2 vaccine is urgently required to limit the spread of RHDV2 and reduce the risk of outbreaks of RHDV2 infection in other countries. ...
... RHDV2 can cause the death of young rabbits aged 2-3 weeks, which suggests that RHDV2 may use different receptors (Le Gall-Recule et al., 2011). RHDV2 has now been reported in many countries in Europe, Australia, Africa, and North America (Abrantes et al., 2013;Camarda et al., 2014;Dalton et al., 2014Dalton et al., , 2012Duarte et al., 2015;Hall et al., 2015;Le Gall-Recule et al., 2011;Martin-Alonso et al., 2016;Neimanis et al., 2018b;Rouco et al., 2019;Westcott et al., 2014), and in many areas, RHDV2 has replaced classic RHDV as the major cause of RHD (Lopes et al., 2014;Mahar et al., 2018;Peacock et al., 2017).Most strikingly, RHDV2 can cause the death of classic RHDV-vaccinated rabbits (Peacock et al., 2017), which suggests that RHDV2 differs antigenically from classic RHDV. Therefore, an RHDV2 vaccine is urgently required to limit the spread of RHDV2 and reduce the risk of outbreaks of RHDV2 infection in other countries. ...
... However, other studies using more recent RHDV2 isolates report very high levels of virulence in both adult and young rabbits (Capucci, Cavadini, Schiavitto, Lombardi, & Lavazza, 2017;Neimanis, Pettersson, Huang, Widén, & Strive, 2018). Unlike RHDV (Robinson, So, Müller, Cooke, & Capucci, 2002), RHDV2 causes fatal infections in juvenile rabbits <5 weeks of age (Neave et al., 2018) and can also infect rabbits recovered from previous RHDV infection or vaccination (Le Gall-Reculé et al., 2013;Neave et al., 2018;Peacock et al., 2017). Initial estimates of the impact of RHDV2 on wild populations from two sites in South Australia indicated a reduction in rabbit abundance of around 80% . ...
... Similarly, reductions in juvenile recruitment by RHDV2 would also negatively affect RCVA transmission.The reciprocal positive association between RHDV and the rate of increase of RHDV2 was most likely the result of partial cross-immunity, where some RHDV seropositive individuals are susceptible to RHDV2 infection. RHDV2 can overcome immunity from previous RHDV infection or vaccination (LeGall-Reculé et al., 2013;Neave et al., 2018;Peacock et al., 2017) and partial cross-immunity has been recognized F I G U R E 6 Estimated average trends (parameter A-Equation 5) in the seroprevalence of RCVA, RHDV and RHDV2 for juvenile (≤150 days old) and adult (>150 days) rabbits following the arrival of RHDV2 at each site TA B L E 3 Table of parameter estimates for the matrix B describing the effect of antibody prevalence for a strain at time t−1 (columns) on the change in antibody prevalence for a strain at time t (rows). Values in bold indicate interactions between strains that have 95% credible intervals that do not include zero. ...
Multi‐strain, host‐disease dynamics describe a system where multiple strains of a pathogen compete for susceptible individuals of a single host. The theoretical properties of these systems have been well studied, but there are few empirical studies in wildlife hosts.
We examined the impacts of two novel strains of rabbit haemorrhagic disease virus (RHDV) recently introduced into Australia, one inadvertently (RHDV2) and one deliberately for rabbit biocontrol (RHDV‐K5), by analysing long‐term monitoring data for introduced European rabbits Oryctolagus cuniculus from 18 sites throughout Australia. We examined population‐level impacts using rabbit spotlight counts pre‐ and post‐arrival of the two strains. We also analysed serological data to determine potential interactions among the introduced and existing field strains of RHDV, as well as a pre‐existing benign strain of calicivirus (RCV‐A1).
Serological analyses suggested that RHDV2 arrived in Australia during spring 2014 and spread rapidly through the Australian rabbit population within 2 years. Following the establishment of RHDV2, rabbit abundance was reduced by an average of 60%, with impacts most pronounced in South and Western Australia. In contrast, the deliberate release of RHDV‐K5 had little impact on rabbit populations.
Although RHDV2 has spread rapidly throughout Australia, our serological analyses do not support the observation that RHDV2 is rapidly replacing existing field strains of RHDV, as was previously reported in Australia and Europe. Nevertheless, RHDV2 has negatively impacted the ability of RHDV and RCV‐A1 to spread within rabbit populations, most likely due to its ability to infect juvenile rabbits, thereby removing them from the pool of susceptible individuals available to be infected by competing strains.
Synthesis and applications. The impact of the release of a novel strain of rabbit haemorrhagic disease virus (RHDV‐K5) for rabbit biocontrol in Australia has been suppressed by the emergence of a competing strain, RHDV2. Hence, the success of further releases of similar RHDV strains for rabbit biocontrol appears doubtful. Despite this, RHDV2 has suppressed rabbit abundances by an average of 60%, with impacts most pronounced in South and Western Australia. Whether the incursion of RHDV2 leads to the competitive exclusion of other endemic RHDV strains remains to be resolved. However, the existence of partial cross‐immunity could allow some level of coexistence between RHDV2 and RHDV strains, at least in the medium term.
... RHDV2 (RHDVb/GI.2) has been reported in France [3], Italy [7], the Iberian Peninsula [8,9], Sardinia [10], the United Kingdom [11], Madeira [12], the Canary Islands, the Azores [13], Australia [14], Scandinavia [15], Africa [16] and America [17]. In Sweden, Australia and on the Iberian Peninsula, all recent cases of RHD in wild and domestic rabbits were caused by RHDV2, which suggests that RHDV2 replaces RHDV as the main cause of RHD [8,[18][19][20]. These outbreaks clearly indicated that RHDV2 is antigenically different from RHDV and has the capacity to kill rabbits vaccinated against RHDV [20,21]. ...
... In Sweden, Australia and on the Iberian Peninsula, all recent cases of RHD in wild and domestic rabbits were caused by RHDV2, which suggests that RHDV2 replaces RHDV as the main cause of RHD [8,[18][19][20]. These outbreaks clearly indicated that RHDV2 is antigenically different from RHDV and has the capacity to kill rabbits vaccinated against RHDV [20,21]. ...
Rabbit haemorrhagic disease virus (RHDV) type 2 (GI.2/RHDV2/b) is an emerging pathogen in wild rabbits and in domestic rabbits vaccinated against RHDV (GI.1). Here we report the genome sequence of a contemporary RHDV2 isolate from the Netherlands and investigate the immunogenicity of virus-like particles (VLPs) produced in insect cells. RHDV2 RNA was isolated from the liver of a naturally infected wild rabbit and the complete viral genome sequence was assembled from sequenced RT-PCR products. Phylogenetic analysis based on the VP60 capsid gene demonstrated that the RHDV2 NL2016 isolate clustered with other contemporary RHDV2 strains. The VP60 gene was cloned in a baculovirus expression vector to produce VLPs in Sf9 insect cells. Density-gradient purified RHDV2 VLPs were visualized by transmission electron microscopy as spherical particles of around 30 nm in diameter with a morphology resembling authentic RHDV. Immunization of rabbits with RHDV2 VLPs resulted in high production of serum antibodies against VP60, and the production of cytokines (IFN-γ and IL-4) was significantly elevated in the immunized rabbits compared to the control group. The results demonstrate that the recombinant RHDV2 VLPs are highly immunogenic and may find applications in serological detection assays and might be further developed as a vaccine candidate to protect domestic rabbits against RHDV2 infection.
... Rabbit population monitoring using vehicle-based spotlight transect counts began at IFRNP in February 1992 and the current 23.7 km transects had been counted quar- terly in most years since 2002, 29 but with no counts in 2015 and one or two missing counts in three other recent years. RHDV2 was identified from liver or bone marrow of carcases collected at monitoring sites using PCR and ge- netic sequencing (details in ref 33 ). ...
... We cannot be certain that the population declines are entirely attributable to RHDV2, even though it has largely displaced earlier GI.1 RHDV variants in Aus- tralia 35 and caused high mortality in rabbits that were immune to those earlier variants. 33 Recently emerged, virulent myxoma viruses 36 appear to have contributed to the decline at Turretfield in April 2016. Synergistic effects between the two diseases may also be impor- tant if population-level susceptibility to myxomatosis increased due to RHDV2-induced mortality in old rab- bits which were immune to both GI.1 RHDV and myx- omatosis. ...
Recent analyses of geographical variation in cats? diet across Australia have been used to highlight rabbit control as a conservation risk, on the basis that prey-switching by cats following rabbit control is likely to threaten Australian fauna. There is no direct evidence to support that proposition. However, there is direct evidence of repeated prey-switching due to seasonal fluctuations in uncontrolled rabbit populations, of long-term suppression of rabbit numbers by effective rabbit control, and that reduced rabbit abundance leads to reduced cat abundance, reduced predation of native fauna and recovery of threatened prey populations. Furthermore, rabbits are a known threat to many Australian native plants and rabbit control has proven benefits for their recovery, thereby offering long-term benefits for dependent fauna and broader ecosystem function. On the balance of evidence, rabbit control should be encouraged in Australia wherever possible, as a national conservation priority.
... Er zijn wel ooggetuigenverklaringen en lokale afschotgegevens van voor, tijdens en na de uitbraak van de virusziekte myxomatose in midden jaren '50 (Wallage- Drees 1988). Daarnaast zijn krantenartikelen uit die tijd een bron van informatie over het verloop van de virusziekte en het herstel daarvan (Dekker, in prep (Peacock et al. 2017). Deze tweede variant zorgde dus wederom voor een afname van populaties. ...
In dit rapport worden op basis van de wetenschappelijke literatuur een aantal practische aanbevelingen gegeven voor herstelmaatregelen voor de populaties van de vijf soorten van de wildlijst. Het gaat om fazant, wilde eend, houtduif, haas en konijn.
This report provides a number of practical recommendations for recovery measures for the populations of the five species on the game list, based on scientific literature. These are pheasant, mallard, wood pigeon, hare and rabbit.
... Similar to the previously known RHDV of rabbits (termed RHDV1), recent isolates of RHDV2 are highly virulent, causing infectious hepatitis with high case fatality rates in susceptible rabbits (Oryctolagus cuniculus) [7]. However, in contrast to RHDV1, RHDV2 has a broader host range within the order Lagomorpha and is able to infect various species of hares (Lepus sp.) and cottontails (Sylvilagus sp.) [8][9][10], and can fatally infect rabbits that are resistant to infection with virulent RHDV1 at a very young age [11,12]. Furthermore, recent work has shown that this ability to infect young rabbits enables RHDV2 to amplify in susceptible populations earlier [13]. ...
Following the arrival of rabbit haemorrhagic disease virus 2 (RHDV2) in Australia, average rabbit population abundances were reduced by 60% between 2014 and 2018 based on monitoring data acquired from 18 sites across Australia. During this period, as the seropositivity to RHDV2 increased, concurrent decreases were observed in the seroprevalence of both the previously circulating RHDV1 and RCVA, a benign endemic rabbit calicivirus. However, the detection of substantial RHDV1 seropositivity in juvenile rabbits suggested that infections were continuing to occur, ruling out the rapid extinction of this variant. Here we investigate whether the co-circulation of two pathogenic RHDV variants was sustained after 2018 and whether the initially observed impact on rabbit abundance was still maintained. We monitored rabbit abundance and seropositivity to RHDV2, RHDV1 and RCVA at six of the initial eighteen sites until the summer of 2022. We observed sustained suppression of rabbit abundance at five of the six sites, with the average population reduction across all six sites being 64%. Across all sites, average RHDV2 seroprevalence remained high, reaching 60–70% in adult rabbits and 30–40% in juvenile rabbits. In contrast, average RHDV1 seroprevalence declined to
... europaeus) GI.1 or rabbit haemorrhagic disease virus (RHDV), now also referred to as acute hepatitis, was first recorded over 30 years ago (24), its mechanism of pathogenesis is still not well understood. It is assumed that the main pathogenic phenomenon of this virus is its affinity to the endothelium of blood vessels, which leads to disseminated intravascular coagulation (DIC) syndrome (1,24) as a result of changes in the liver, including those manifested by apoptosis and necrosis of hepatocytes (3,11,22,30,34,38,42). Other important symptoms related to the pathogenesis of this disease caused by L. europaeus GI.1 (RHDV) are changes in animal immunity determined by the role of neutrophils, which are the first line of defence against this infection (19,31,40,41). ...
Introduction
Lagovirus europaeus is a single-stranded RNA virus causing an acute fatal disease in wild and domestic rabbits around the world. Studies have shown that the pivotal process impacting the immune response against the disease is apoptosis, registered mainly in hepatocytes and in peripheral blood, together with an increased number of cytotoxic lymphocytes (CTLs). It is known that cytotoxic lymphocytes can induce target cells to undergo apoptosis on the pseudoreceptor pathway, such apoptosis having been found in several acute and chronic viral infections. The study aimed to assess the crosstalk between the apoptosis of peripheral blood lymphocytes and CD8+ T lymphocytes (as CTLs) in rabbits infected with 6 Lagovirus europaeus GI.1a viruses.
Material and Methods
Sixty rabbits of Polish hybrid breed comprising both sexes and weighing 3.2–4.2 kg were the experimental group, and an identical group was the control. Each of the six GI.1a Lagovirus europaeus viruses was inoculated into ten experimental rabbits. Control rabbits received glycerol as a placebo. Flow cytometric analysis was performed on blood from the study and control group animals for peripheral blood lymphocyte apoptosis and CTL percentage determination.
Results
The activation of apoptosis in peripheral blood lymphocytes was recorded from 4 h post inoculation (p.i.) up to 36 h p.i. The percentage of CTLs in the total blood pool decreased from 8 to 36 h p.i. A negative correlation between apoptosis of lymphocytes and the number of CTLs was proven.
Conclusion
This may be the first evidence of virus-induced CTL apoptosis in Lagovirus europaeus GI.1a infection.
... In a very short time, the virus has spread throughout the world and is threatening the national economies of countries that, for the most part, rely on the rabbit industry for their economies (12). The disease is now established in Europe, Asia, Africa, and Australia (4,5,17). All outbreaks of RHD until 2010 were caused by L. europaeus strains of genotype GI.1 (RHDV) and its antigenic variants (GI.1a to GI.1d) (12). ...
Lagovirus europaeus (rabbit hemorrhagic disease virus [RHDV]) is a small, nonenveloped, single-stranded RNA virus that causes a severe, highly infectious, and fatal disease in rabbits (Oryctolagus cuniculus) called rabbit hemorrhagic disease (RHD). Since its discovery in the 1980s, it has posed a very serious threat to the global rabbit industry and the rabbit population in the wild. According to data from 2005 to 2018, the occurrence of RHD has been reported or suspected in 50 countries, with more than one-half of the reports being recorded in European countries. The main aim of the study was to detect Lagovirus europaeus (RHDV) strains found in domestic rabbits that died suddenly in the city of Wrocław in southwest Poland. All animals (n = 14) tested in this study died naturally and showed macroscopic features at necropsy that indicated the possibility of death from RHD. As a result of the research, the presence of L. europaeus virus was confirmed in 8 samples of all 14 samples collected. All strains of Lagovirus europaeus isolated in the present study showed 100% nucleotide identity to L. europaeus GI.1 strain FRG and a strain isolated in New Zealand, as well as the L. europaeus GI.1a Erfurt strain. This suggests that it is likely that L. europaeus GI.2 strains have so far not displaced L. europaeus GI.1 strains from the environment in Poland.
IMPORTANCE Lagovirus europaeus (RHDV) causes a severe, highly infectious, and fatal disease in rabbits called RHD. The disease is a very serious threat to the global rabbit industry and the rabbit population in the wild. The aim of the study was to detect Lagovirus europaeus (RHDV) strains in domestic rabbits that died suddenly in Poland. The presence of RHDV was confirmed in 8 samples of all 14 samples collected. This is one of the very few reports on the existence of this virus in pet rabbits in Poland.
... This is reminiscent of previous reports on the partial cross-protection to GI.1 challenge conveyed by GI.4 immunity, which rapidly declined within weeks following the GI.4 infection [16]. Overall, our findings contrast with previous reports in Europe where there appears to be more limited cross-protection between variants [15,17], as well as reports of GI.1-immune rabbits succumbing to GI.2 in Australia [32], although the time between infections with the two viruses was unknown in that study. ...
The use of rabbit hemorrhagic disease virus (RHDV) as a biocontrol agent to control feral rabbit populations in Australia, in combination with circulating endemic strains, provides a unique environment to observe the interactions between different lagoviruses competing for the same host. Following the arrival of RHDV2 (GI.2) in Australia, it became necessary to investigate the potential for immunological cross-protection between different variants, and the implications of this for biocontrol programs and vaccine development. Laboratory rabbits of various immune status—(1) rabbits with no detectable immunity against RHDV; (2) rabbits with experimentally acquired immunity after laboratory challenge; (3) rabbits immunised with a GI.2-specific or a multivalent RHDV inactivated virus prototype vaccine; or (4) rabbits with naturally acquired immunity—were challenged with one of three different RHDV variants (GI.1c, GI.1a or GI.2). The degree of cross-protection observed in immune rabbits was associated with the variant used for challenge, infectious dose of the virus and age, or time since acquisition of the immunity, at challenge. The immune status of feral rabbit populations should be determined prior to intentional RHDV release because of the high survival proportions in rabbits with pre-existing immunity. In addition, to protect domestic rabbits in Australia, a multivalent RHDV vaccine should be considered because of the limited cross-protection observed in rabbits given monovalent vaccines.
... Despite this, detailed infection and case fatality rates from RHDV2 infection remain unknown in wild rabbits. The ability of RHDV2 to lethally infect rabbits with acquired immunity to other RHDV strains (and vice versa) also remains unquantified in wild rabbits (Calvete et al., 2018;Le Gall-Reculé et al., 2013;Peacock et al., 2017). Furthermore, as RHDV2 occurs naturally in Australia, acquired immunity to non-lethal RHDV2 infection is likely to influence the effectiveness of intentional releases of other RHDVs (CZECH or K5) by landholders if there is partial immunological cross protection. ...
Rabbit haemorrhagic disease virus 2 (RHDV2) is now the dominant calicivirus circulating in wild rabbit populations in Australia. This study compared the infection and case fatality rates of RHDV2 and two RHDVs in wild rabbits, as well as their ability to overcome immunity to the respective other strains. Wild rabbits were allocated to groups either blindly or based on prescreening for RHDV/RHDV2 antibodies at capture. Rabbits were monitored regularly until their death or humane killing at 7 days post infection. Liver and eyeball samples were collected for lagovirus testing and aging rabbits, respectively. At capture, rabbits showed high seroprevalence to RHDV2 but not to RHDV. In RHDV/RHDV2 seronegative rabbits at capture, infection rates were highest in those inoculated with RHDV2 (81.8%, 18/22), followed by K5 (53.8%, 7/13) and CZECH (40.0%, 2/5), but these differences were not statistically significant. In rabbits with previous exposure to RHDV2 at capture, infection rates were highest when inoculated with K5 (59.6%, 31/52) followed by CZECH (46.0%, 23/50), with infection rates higher in younger rabbits for both viruses. In RHDV/RHDV2 seronegative rabbits at capture, case fatality rates were highest for those inoculated with K5 (71.4%), followed by RHDV2 (50.0%) and CZECH (50.0%). In rabbits with previous exposure to RHDV2 at capture, case fatality rates were highest in rabbits inoculated with K5 (12.9%) followed by CZECH (8.7%), with no case fatalities following RHDV2 inoculation. Case fatality rates did not differ significantly between inoculums in either serostatus group at capture. Based on multivariable modelling, time to death post RHDV inoculation increased in rabbits with recent RHDV2 exposure compared to seronegative rabbits and with age. The results suggest that RHDV2 may cause higher mortalities than other variants in seronegative rabbit populations but that K5 may be more effective in reducing rabbit populations in an RHDV2‐dominant landscape. This article is protected by copyright. All rights reserved
... A similar pattern has been described in several other countries [19,51,52]. The reasons for this competitive advantage may be multifactorial, and include RHDV2 being capable of partially overcoming RHDV1 host immunity, where it exists [53], that RHDV2 has a wider host breadth [54], and the additional ability to cause disease in younger cohorts relative to RHDV1 [55,56]. Taggart et al. [56] identified the latter characteristic of RHDV2 as particularly important, as clinical infections of kittens can lead to high viral replication, shedding into the environment, and mortality. ...
Rabbit haemorrhagic disease virus 2 (RHDV2; GI.2) is a pathogenic lagovirus that emerged in 2010, and which now has a global distribution. Outbreaks have been associated with local population declines in several lagomorph species, due to rabbit haemorrhagic disease (RHD)-associated mortality raising concerns for its potential negative impact on threatened or vulnerable wild populations. The Irish hare (Lepus timidus hibernicus) is endemic to Ireland, and is of conservation interest. The first cases of RHDV2 in Ireland were reported in domestic rabbits (Oryctolagus cuniculus) in 2016, soon followed by the first known case in a wild rabbit also in 2016, from a population reported to be experiencing high fatalities. During summer 2019, outbreaks in wild rabbits were confirmed in several locations throughout Ireland. Six cases of RHDV2 in wild hares were confirmed between July and November 2019, at four locations. Overall, 27 cases in wildlife were confirmed in 2019 on the island of Ireland, with a predominantly southern distribution. Passive surveillance suggests that the Irish hare is susceptible to lethal RHDV2 infection, and that spillover infection to hares is geographically widespread in eastern areas of Ireland at least, but there is a paucity of data on epidemiology and population impacts. A literature review on RHD impact in closely related Lepus species suggests that intraspecific transmission, spillover transmission, and variable mortality occur in hares, but there is variability in reported resistance to severe disease and mortality amongst species. Several key questions on the impact of the pathogen in Irish hares remain. Surveillance activities throughout the island of Ireland will be important in understanding the spread of infection in this novel host.
... RHDV2 also causes disease in young rabbits, which show an age-dependent innate resistance to lethal disease caused by RHDV1 despite being permissive to infection [9]. RHDV2 is antigenically distinct from RHDV1, overcoming both infection-induced and vaccinal immunity [10,11]. ...
Rabbit haemorrhagic disease virus 2 (RHDV2) is a lagovirus in the family Caliciviridae. The closely related Rabbit haemorrhagic disease virus (RHDV, termed RHDV1 throughout this manuscript for clarity) has been used extensively as a biocontrol agent in Australia since the mid-1990s to manage wild rabbit populations, a major economic and environmental pest species. Releasing RHDV1 into populations with a high proportion of rabbits less than 8-10 weeks of age leads to non-lethal infection in many of these young animals, with subsequent seroconversion and long-term immunity against reinfection. In contrast, RHDV2 causes lethal disease even in young rabbits, potentially offering substantial benefits for rabbit management programs over RHDV1. However, it is not clear how acquired resistance from maternal antibodies may influence immunity after RHDV2 infection. In this study, we assessed serological responses after RHDV2 challenge in young rabbits of three different ages (5-, 7-, or 9-weeks-old) that were passively immunised with either high- (titre of 2560 by RHDV IgG ELISA; 2.41 mg/mL total protein) or low- (titre of 160-640 by RHDV IgG ELISA; 1.41 mg/mL total protein) dose RHDV2 IgG to simulate maternal antibodies. All rabbits treated with a high dose and 75% of those treated with a low dose of RHDV2 IgG survived virus challenge. Surviving animals developed robust lagovirus-specific IgA, IgM, and IgG responses within 10 days post infection. These findings demonstrate that the protection against RHDV2 conferred by passive immunisation is not sterilising. Correspondingly, this suggests that the presence of maternal antibodies in wild rabbit populations may impede the effectiveness of RHDV2 as a biocontrol.
... Subsequently, the data obtained from flock sample history and phylogenetic analysis proved that all ages and breeds of rabbits become susceptible to that disease. This agreed with Le Gall-Reculé et al., 2011 andPeacock et al., 2017 who said that a virus, had a capsid protein sequence identity of about 80 per cent with RHDV2, was able to cause RHD in vaccinated and young rabbits (15-25 days old). While, Ewees. ...
... In late 2014, RHDV2 entered Australia by an unknown route. The ability to infect rabbits that are immune to RHDV1 and cause disease in young kittens appears to have enabled successful invasion of the wild rabbit population partially replacing RHDV1 [93][94][95][96][97][98]. It is estimated that population losses due to RHDV2 averaged around 60% across Australian rabbit populations [99]. ...
Viral diseases, whether of animals or humans, are normally considered as problems to be managed. However, in Australia, two viruses have been used as landscape-scale therapeutics to control European rabbits (Oryctolagus cuniculus), the preeminent invasive vertebrate pest species. Rabbits have caused major environmental and agricultural losses and contributed to extinction of native species. It was not until the introduction of Myxoma virus that effective control of this pest was obtained at a continental scale. Subsequent coevolution of rabbit and virus saw a gradual reduction in the effectiveness of biological control that was partially ameliorated by the introduction of the European rabbit flea to act as an additional vector for the virus. In 1995, a completely different virus, Rabbit hemorrhagic disease virus (RHDV), escaped from testing and spread through the Australian rabbit population and again significantly reduced rabbit numbers and environmental impacts. The evolutionary pressures on this virus appear to be producing quite different outcomes to those that occurred with myxoma virus and the emergence and invasion of a novel genotype of RHDV in 2014 have further augmented control. Molecular studies on myxoma virus have demonstrated multiple proteins that manipulate the host innate and adaptive immune response; however the molecular basis of virus attenuation and reversion to virulence are not yet understood.
... By 2016, outbreaks were killing rabbits in rescue centres, breeding colonies and show rabbits as well as individual pets (Harcourt-Brown 2016, Rocchi & Dagleish 2018). Immunity against RHDV1 does not protect against RHDV2 (Le Gall-Reculé et al. 2013, Peacock et al. 2017 and deaths occurred in rabbits that were vaccinated against RHDV1 with Nobivac Myxo-RHD (MSD Animal Health), which was the only vaccine available in the UK at the outset of the RHDV2 epidemic. In 2016, adjuvanted inactivated vaccines against RHDV2, such as Eravac (Hipra Laboratories, Spain) and Filavac VHD K C + V (Filavie Laboratories, France) started to be imported (Saunders 2016) and, by 2018, both vaccines had product licences and were available in the UK. ...
Objective
To report PCR results and vaccination status of rabbits with rabbit haemorrhagic disease following an investigation into sudden or unexpected death.
Materials and Methods
PCR testing for RHDV2 and RHDV1 was performed on rabbit liver samples at two laboratories. Laboratory A reported results as positive or negative; Laboratory B reported results quantitatively as RNA copies per mg liver, categorised as negative, inconclusive or positive. The vaccination status of rabbits with both histopathological features of rabbit haemorrhagic disease and positive PCR test results were collated.
Results
PCR results matched histopathological findings in 188 of 195 (96%) cases. Seven individuals showed equivocal results, all of which had histopathological features of RHD but three tested PCR‐negative and four results conflicted between laboratories. RHDV2 was the serotype detected in all PCR‐positive cases. Histological features of rabbit haemorrhagic disease and PCR test results were positive in 125 rabbits; 51 unvaccinated, 56 in‐date with Nobivac Myxo‐RHD and 13 vaccinated against RHDV2 – although nine of these were vaccinated within 10 days of death.
Clinical Significance
PCR testing complements histopathology in cases of sudden death in rabbits by confirming the diagnosis and identifying virus serotype, but there can be false negatives. Although RHDV2 is currently prevalent in UK pet rabbits, vaccination against both RHDV1 and RHDV2 is recommended. Failures of RHDV2 vaccine are infrequent.
... In addition, the mortality observed in rabbits diagnosed with RHD that have had infection with classical strains of the virus and acquired immunity against RHDV in this way, shows the lack of cross-protection between RHDV2 and RHDV. This fact was of great importance for the new pathogen, which obtained such a large range in a relatively short time Peacock et al., 2017), which is why it became urgent to develop a vaccine against RHDV2. The inactivated vaccines introduced at the beginning were prepared from rabbit liver extracts that were infected under experimental conditions. ...
RHD (Rabbit Haemorrhagic Disease) is an etiologic agent that causes viral haemorrhagic
disease of rabbits, which is also referred to as rabbit plague. The desire to explore knowledge about this pathogen in the world results not only from its similarity to human hemorrhagic fevers, for which RHDV can be considered as a good research model. It is also important that with myxomatosis, rabbit plague is the most severe viral disease of these animals. Describing the classic RHDV virus, followed by RHDVa, which is considered the first described antigenic variant of the RHD virus, allowed to become familiar with the information that until now constituted the basic building block of the control of viral haemorrhagic disease of rabbits in the world. However, the attributes of RHDV2, characterized only in 2010, differ significantly from the specifics of RHDV strains known to date. What’s more, the global expansion of this pathogen has significantly changed the RHD image, the methods of its identification, control and eradication. The completely changed face of the virus that causes rabbit plague causes that the belief about full supervision over RHD is now obsolete.
... countries in Europe, Australia, Africa, and North America [7][8][9][12][13][14][15][16][17][18][19] and has replaced classic RHDV as the major cause of RHD in many areas [20][21][22]. ...
Background:
Rabbit Hemorrhagic Disease Virus (RHDV) belongs to the Caliciviridae family, is a highly lethal pathogen to rabbits. Increasing numbers of studies have demonstrated the existence of antigenic variation in RHDV, leading to the emergence of a new RHDV isolate (RHDVb). However, the underlying factors determining the emergence of the new RHDV and its unpredictable epidemiology remain unclear. To investigate these issues, we selected more than 184 partial and/or complete genome sequences of RHDV from GenBank and analyzed their phylogenetic relationships, divergence, and predicted protein modification sites.
Results:
Phylogenetic analysis showed that classic RHDV isolates, RHDVa, and RHDVb formed different clades. It's interesting to note that RHDVa being more closely related to classic RHDV than RHDVb, while RHDVb had a closer genetic relationship to Rabbit Calicivirus (RCV) than to classic RHDV isolates. Moreover, divergence analysis suggested that the accumulation of amino acid (aa) changes might be a consequence of adaptive diversification of capsid protein (VP60) during the division between classical RHDV, RHDVa, RHDVb, and RCV. Notably, the prediction of N-glycosylation sites suggested that RHDVb subtypes had two unique N-glycosylation sites (aa 301, 362) but lacked three other N-glycosylation sites (aa 45, 308, 474) displayed in classic RHDV and RHDVa VP60 implying this divergence of N-glycosylation sites in RHDV might affect viral virulence. Analysis of phosphorylation sites also indicated that some phosphorylation sites in RHDVa and RHDVb differed from those in classic RHDV, potentially related to antigenic variation in RHDV.
Conclusion:
The genetic relationship between RHDVb and RCV was closer than classic RHDV isolates. Moreover, compared to RHDV and RHDVa, RHDVb had two unique N-glycosylation sites but lacked three sites, which might affect the virulence of RHDV. These results may provide new clues for further investigations of the origin of new types of RHDV and the mechanisms of genetic variation in RHDV.
... The antigenic profile of GI.2 differs to a high degree when compared to both GI.1 and its variant GI.1a on the viral surface, where neutralizing epitopes are located [13]. Furthermore, it has been established that GI.1-based vaccines confer only limited cross-protection against GI.2 [28]. In Tunisia, until recently, all rabbits were administered vaccines derived from GI.1. ...
Two distinct genotypes responsible for rabbit hemorrhagic disease (RHD) are reported, GI.1 (RHDV) and GI.2 (RHDV2). Vaccines based on these two genotypes are only partially cross-protective. Hence, knowing which genotype is circulating is important for appropriate control measures. We have investigated 25 field samples isolated between 2015 and 2018 from rabbits with clinical signs of RHD. Only GI.2 (RHDV2) is currently circulating in Tunisia. All Tunisian samples were grouped together with typical genotypic and phenotypic mutations. Therefore, we recommend initiating an extensive preventive vaccination program based on GI.2 vaccines in addition to a regular monitoring of the circulating lagoviruses.
... Current animal calicivirus vaccines have biological and logistical shortfalls that limit their efficacy. For example, the RHDV-1 vaccine provides poor cross-protection against RHDV-2, whilst the RHDV-2 vaccine has had limited testing and is currently available only in the UK [8,[13][14][15]. Similarly, approved FCV vaccines (including strains F9, 255, 431 and G1) do not provide complete protection against the antigenically distinct virulent systemic FCV (VS-FCV) [7,16,17]. ...
The widespread nature of calicivirus infections globally has a substantial impact on the health and well-being of humans and animals alike. Currently, the only vaccines approved against caliciviruses are for feline and rabbit-specific members of this group, and thus there is a growing effort towards the development of broad-spectrum antivirals for calicivirus infections. In this study, we evaluated the antiviral activity of the adenosine analogue NITD008 in vitro using three calicivirus model systems namely; feline calicivirus (FCV), murine norovirus (MNV), and the human norovirus replicon. We show that the nucleoside analogue (NA), NITD008, has limited toxicity and inhibits calicivirus replication in all three model systems with EC50 values of 0.94 μM, 0.91 µM, and 0.21 µM for MNV, FCV, and the Norwalk replicon, respectively. NITD008 has a similar level of potency to the most well-studied NA 2′-C-methylcytidine in vitro. Significantly, we also show that continual NITD008 treatment effectively cleared the Norwalk replicon from cells and treatment with 5 µM NITD008 was sufficient to completely prevent rebound. Given the potency displayed by NITD008 against several caliciviruses, we propose that this compound should be interrogated further to assess its effectiveness in vivo. In summary, we have added a potent NA to the current suite of antiviral compounds and provide a NA scaffold that could be further modified for therapeutic use against calicivirus infections.
... This virus, termed RHDV2, in contrast to the original RHDV1s and RHDV1 K5, can affect a very high proportion of young rabbits. In addition, RHDV2 has been shown to overcome acquired immunity due to prior exposure to RHDV1 (Peacock et al. 2017;Calvete et al, 2018) and has been reported to infect and kill several hare species including the European brown hare (Lepus While preparations for the planned K5 release in March 2017 were well-advanced, RHDV2 had reached Western Australia and Tasmania, and RHDV2 outbreaks were re-occurring in the eastern States. Wild rabbits as well as domestic rabbits kept as pets and bred for meat and medical research were affected. ...
The viral biocontrol agents Myxoma virus (MYXV) and Rabbit Haemorrhagic Disease Virus (RHDV1), released in 1950 and 1996 respectively, are the only control tools to have resulted in significant and lasting landscape-scale suppression of rabbit populations in Australia. Multiple conservation benefits and significant economic savings have resulted from the long-term and widespread reductions in rabbit numbers and impacts. In an effort to ‘boost’ rabbit biocontrol, an additional variant of RHDV1 ('K5') was recently released nationwide to counteract the decreasing effectiveness of both RHDV1 and MYXV that results from the evolutionary ‘arms race’ between viruses and their hosts. Two years prior to the K5 release, an exotic RHDV strain (RHDV2) appeared in Australia. The commercially available vaccine used to protect pet and farmed rabbits against the officially released K5 was ineffective against the exotic RHDV2, resulting in numerous deaths of domestic rabbits. This created substantial confusion about which strain was released as a biocontrol tool, as well as renewed concerns amongst pet rabbit owners and rabbit farmers about the use of viruses as lethal rabbit control tools in general. Ongoing effective control of wild rabbits in Australia is absolutely essential to protect the substantial conservation gains made by the long-term suppression of rabbit numbers over the past decades, and there is currently no alternative population control tool to achieve this at the required landscape scale. Vaccine formulations need updating to protect non-target farmed and pet rabbits from circulating field variants, including RHDV2, and to increase public acceptance for the ongoing use of viral biocontrol for feral rabbit populations.
... Due to the limited information of the vaccination status of domestic rabbits in this study and, perhaps more importantly, the lack of information about numbers of vaccinated rabbits that have survived GI.2 infection, it is not possible to estimate the effectiveness of the GI.1 vaccine in preventing disease caused by GI.2. However, the detection of GI.2 in 15 vaccinated domestic rabbits supports previous work demonstrating that cross-protection between GI.1 and GI.2 is at best incomplete, and a vaccine covering GI.2 is urgently needed to protect farmed and pet rabbits in Australia (20). ...
Rabbit hemorrhagic disease virus 2 (RHDV2; Lagovirus GI.2) is a pathogenic calicivirus that affects European rabbits (Oryctolagus cuniculus) and various hare (Lepus) species. GI.2 was first detected in France in 2010 and subsequently caused epidemics in wild and domestic lagomorph populations throughout Europe. In May 2015, GI.2 was detected in Australia. Within 18 months of its initial detection, GI.2 had spread to all Australian states and territories and rapidly became the dominant circulating strain, replacing Rabbit hemorrhagic disease virus (RHDV/GI.1) in mainland Australia. Reconstruction of the evolutionary history of 127 Australian GI.2 isolates revealed that the virus arrived in Australia at least several months before its initial description and likely circulated unnoticed in wild rabbit populations in the east of the continent prior to its detection. GI.2 sequences isolated from five hares clustered with sequences from sympatric rabbit populations sampled contemporaneously, indicating multiple spillover events into hares rather than an adaptation of the Australian GI.2 to a new host. Since the presence of GI.2 in Australia may have wide-ranging consequences for rabbit biocontrol, particularly with the release of the novel biocontrol agent GI.1a/RHDVa-K5 in March 2017, ongoing surveillance is critical to understanding the interactions of the various lagoviruses in Australia and their impact on host populations.
Rabbit haemorrhagic disease viruses (RHDV) belong to the family Caliciviridae, genus Lagovirus europaeus, genogroup GI, comprising four genotypes GI.1–GI.4, of which the genotypes GI.1 and GI.2 are pathogenic RHD viruses, while the genotypes GI.3 and GI.4 are non-pathogenic RCV (Rabbit calicivirus) viruses. Among the pathogenic genotypes GI.1 and GI.2 of RHD viruses, an antigenic variant of RHDV, named RHDVa—now GI.1a–RHDVa, was distinguished in 1996; and in 2010, a variant of RHDV—named RHDVb, later RHDV2 and now GI.2–RHDV2/b—was described; and recombinants of these viruses were registered. Pathogenic viruses of the genotype GI.1 were the cause of a disease described in 1984 in China in domestic (Oryctolagus (O.) cuniculus domesticus) and wild (O. cuniculus) rabbits, characterised by a very rapid course and a mortality rate of 90–100%, which spread in countries all over the world and which has been defined since 1989 as rabbit haemorrhagic disease. It is now accepted that GI.1–RHDV, including GI.1a–RHDVa, cause the predetermined primary haemorrhagic disease in domestic and wild rabbits, while GI.2–RHDV2/b cause it not only in rabbits, including domestic rabbits’ young up to 4 weeks and rabbits immunised with rabbit haemorrhagic disease vaccine, but also in five various species of wild rabbits and seven different species of hares, as well as wild ruminants: mountain muskoxen and European badger. Among these viruses, haemagglutination-positive, doubtful and harmful viruses have been recorded and described and have been shown to form phylogenogroups, immunotypes, haematotypes and pathotypes, which, together with traits that alter and expand their infectious spectrum (rabbit, hare, wild ruminant, badger and various rabbit and hare species), are the determinants of their pathogenicity (infectivity) and immunogenicity and thus shape their virulence. These relationships are the aim of our consideration in this article.
Rabbit hemorrhagic disease virus 2 (RHDV2), recently detected in the western United States, has the potential to cause mass mortality events in wild rabbit and hare populations. Currently, few management strategies exist other than vaccination. We developed a spatially explicit model of RHDV2 for a population of riparian brush rabbits ( Sylvilagus bachmani riparius ), a subspecies of brush rabbit classified as endangered in the United States, on a subsection of the San Joaquin River National Wildlife Refuge. The goal of our model was to provide guidance regarding vaccination strategies for an endangered rabbit species. Our model predicts that increased interactions between rabbits (a proxy for landscape connectivity) and disease transmission rates among susceptible hosts (individual brush rabbits and conspecifics) have the greatest influence on the outcome of a potential vaccination campaign. Our model projects that across a range of parameter estimates (given an RHDV2 incursion), the median estimated population size with a 0%–10% vaccination rate after 1 year is 538 rabbits (95% Confidence Interval [C.I.] 69–1235), approximately 36% of the expected size of the study population of 1470 rabbits without an RHDV2 introduction. With a 10%–20%, 20%–30%, or 30%–40% vaccination rate, the median estimated population size increased to 628 rabbits (95% C.I. 130–1298), 723 rabbits (95% C.I. 198–1317), and 774 rabbits (95% C.I. 228–1410), respectively. These estimates represent 43%, 49%, and 53% of the expected population size without an RHDV2 introduction. Overall, a 1% increase in vaccination rate was associated with a six rabbit (95% C.I. 5–7) increase in total remaining population size. This result is dependent on assumptions regarding environmental transmission, home range size (and contact rates of rabbits). Given the relatively short lifespan of rabbits and the potential need for boosters, vaccination programs are most likely to be successful for small target populations where relatively high vaccination rates can be maintained.
Diagnosis of the causes of rapid mortality in on rabbits was carried out on the basis of epidemiological and pathological profiling, using RT-PCR testing, gene sequencing and phylogenetic tree construction. In this experiment, samples were collected from two rabbit farms in Guizhou and Henan Provinces, China. Then the total RNA of liver tissue was extracted by Trizol method for RT-PCR amplification. The results showed that the specific target band was observed at 829 bp of RHDV2 and 591 bp of RHDV by agarose gel electrophoresis. Two different RT-PCR products amplified from one rabbit liver sample were named GZ-RHDV and GZ-RHDV2, respectively, and the other farm was named HN-RHDV and HN-RHDV2. Subsequently, four RT-PCR products amplified from two rabbit liver samples from different farms were selected for gene sequencing respectively, and the gene sequences were uploaded to NCBI for blast analysis. Finally, MEGA-7 software was used to construct the phylogenetic tree. The measured gene sequences were analysed by blast analysis and the amplification products in the liver samples showed a high degree of homology with domestic virus isolates. Among them, GZ-RHDV and HN-RHDV shared 98.50% and 98.69% homology with the Genbank accession number (MK814815.1), GZ-RHDV2 shared 99.35% homology with the Genbank accession number (OQ570963.1), and HN-RHDV2 shared 98.84% homology with the Genbank accession number (OQ570961.1). The above results confirmed that the cause of this mass mortality in rabbits on both farms was co-infection with RHDV and RHDV2. The sequenced liver samples from farms in Guizhou Province were selected to prepare virus suspension, and 60 day old rabbits immunized with RHDV vaccine were subcutaneously injected into the neck to identify the virulence of the virus. After 22 h, the infected rabbits developed typical clinical symptoms. For example, typical blood retention occurred in the mouth and nose, convulsions, opisthotonos, Mucoid secretion of anus, bleeding in liver, lung and heart, congestion and swelling in spleen were found during autopsy. The results showed that the classical vaccine had no protective effect on the mixed infection strain.
Rabbit viral hemorrhagic disease (RHD) and European hare brown liver syndrome (EBHS) are two similar diseases affecting animals of the hare family, caused by closely related lagoviruses and manifesting as an acute and fatal form of hepatitis and thrombohemorrhagic syndrome in all organs, especially the lungs and liver. The two viruses are closely related genetically and antigenically and share approximately 76% identity. The causative agent of EBHS is a virus of genotype GII.1. Various species of hares and Florida rabbits are susceptible to it. VGBV is caused by viruses of two genotypes: RHDV-GI.1 and RHDV-GI.2. The first genotype (RHDV-GI.1) is strictly specific for rabbits. In contrast, the second (RHDV-GI.2) has a broader range of susceptible animals and affects not only hares but also common badgers and red-bellied musk deer. In addition, due to the lack of crossimmunity between RHDV-GI.1 and RHDV-GI.2 and a wide range of hosts, the second genotype displaces the first of the susceptible populations, which makes it more dangerous in epidemiological terms. The diseases have high morbidity and high mortality - up to 90%. Given the high persistence of the virus in the environment, the disease can cause severe economic damage. Disease control is effectively achieved through vaccination, general quarantine, and preventive measures. However, this only applies to VGBV types 1 and 2, for which vaccines exist. Currently, no vaccines are developed against brown liver syndrome in the European hare.
Four pet rabbits (Oryctolagus cuniculus cuniculus) diagnosed with a fatal infection by rabbit hemorrhagic disease virus (RHDV GI.2) were identified in the same week and further investigated. All animals lived in an urban environment (Lisbon, Portugal), were between 8 months and 2 years old and none had been vaccinated against RHDV2 (GI.2). Three animals arrived at the clinic and died shortly afterward and it was only possible to collect material for RT-qPCR (RHDV) test. These rabbits tested positive for RHDV2, with high viral loads. In the fourth case, additional clinical and post-mortem gross and histological evaluations were performed. This 8 month old intact female indoor pet rabbit was presented with apathy, tachypnea and tachycardia. Radiographic projections revealed no clinical revealed no clinical abnormalities. Serum biochemistry revealed a significant increase in AST and ALT with a small hypoglycemia. Abdominal ultrasound revealed an acute hepatitis. Despite hospitalization support, after 30 h of admission, the rabbit lost consciousness and developed anorexia and pyrexia in the last minutes before death. Post-mortem analysis and molecular testing by RT-qPCR, confirmed the diagnosis of RHDV2 (GI.2) infection also with high viral load. In conclusion, this paper reports a case series that demonstrates the severe infectious ability and the high mortality associated with RHDV even in rabbits from urban environments. Furthermore, it highlights the importance of always considering rabbit hemorrhagic disease (RHD) as a differential diagnosis in pet rabbits with non-specific clinical signs, and should warn veterinarians that pet rabbits living indoors can also be infected with a fatal outcome.
Lagovirus europaeus/GI.1 causes a fatal viral condition in rabbits characterized by acute viral hepatitis and disseminated intravascular coagulation. Due to rapid viral and environmental changes variants (Lagovirus europaeus/GI.1a and GI.2) have appeared and few immunological studies were performed. The aim of the study was to determine innate and adaptive immunity parameters in rabbits infected with six Lagovirus europeus/GI.1a viruses. To achieve the goal several methods were used, i.e. cytometry, microscopy, biochemical and cytochemical tests, spectrophotometry. The results show that three immunotypes exists among the studied strains and they differ in innate (mainly) and adaptive immunity, partly depending on hemagglutination. The peak of changes is 24 h post infection in phagocytosis markers of polymorphonuclear cells and CD8⁺ T cells. Lagovirus europaeus/GI.1a strains differ from Lagovirus europaeus/GI.1 in terms of immunological response based on our previous work concerning the same parameters in immunological response against this disease.
The purpose of these studies was to optimize RHDV type 1 and 2 (RHDV1 and RHDV2) inactivation modes to use the obtained antigens in inactivated vaccines and diagnosticums. The inactivating effect of aminoethylethylenimine and β-propiolactone was studied in different concentrations in correlation with the exposure time and temperature. The correlation between the inactivating effect of the compound used and the accepted test conditions (concentration, temperature, and exposure time) was studied on a group of rabbits, each of which was injected intramuscularly with 1 cm3 of the inactivated material sample. At the end of the maximum exposure interval, a control sample of the viral material, kept under the same conditions without any inactivant added was similarly tested. Lethality was considered to evaluate the damaging action in the test and control groups: L = m/n, where m is the number of dead animals; n is the total number of rabbits in the group for testing of the inactivated material sample. The postmortem diagnosis was confirmed by testing the rabbit liver tissue homogenate for relative antigens using ELISA. It was found that aminoethylethylenimine and β-propiolactone did not have the same effect on the studied variants of the virus. In order to preserve at maximum the antigenic structures of the virus, the following inactivation modes were considered to be optimal: for RHDV1-aminoethylethylenimine at a concentration of 0.3% at 37 °C, exposure time – 72 hours, or β-propiolactone at a concentration of 0.1–0.3% at 25–37 °С, exposure time – 24–48 hours; for RHDV2 – aminoethylethylenimine at a concentration of 1% at 37 °C, exposure time – 72 hours, or β-propiolactone at a concentration 0.3% at 25 °С, exposure time – 24 hours.
Rabbit haemorrhagic disease virus (RHDV) is highly pathogenic to European rabbits. Until recently, only one serotype of RHDV was known, GI.1/RHDV. RHDV2/GI.2 is a novel virus that has rapidly spread and become the dominant pathogenic calicivirus in wild rabbits worldwide. It is speculated that RHDV2 has three competitive advantages over RHDV: 1) the ability to partially overcome immunity to other variants; 2) the ability to clinically infect young rabbits; and 3) a wider host range. These differences would be expected to influence virus transmission dynamics. We used markers of recent infection (IgM/IgA antibodies) to investigate virus transmission dynamics pre‐ and post‐ the arrival of RHDV2. Our dataset contained over 3900 rabbits sampled across a seven‐year period at 12 Australian sites. Following the arrival of RHDV2, seasonal peaks in IgM and IgA seropositivity shifted forward one season; from winter to autumn and spring to winter, respectively. Contrary to predictions, we found only weak effects of rabbit age, seropositivity to non‐pathogenic calicivirus RCV‐A1 and population abundance on IgM/IgA seropositivity. Our results demonstrate that RHDV2 enters rabbit populations shortly after the commencement of annual breeding cycles. Upon entering the population RHDV2 undergoes extensive replication in young rabbits, causing clinical disease, high virus shedding, mortality and the creation of virus‐laden carcasses. This results in high virus contamination in the environment, furthering the transmission of RHDV2 and initiating outbreaks, whilst simultaneously removing the susceptible cohort required for the effective transmission of RHDV. Although RHDV may enter the population at the same time point, it is sub‐clinical in young rabbits, causing minimal virus shedding and low environmental contamination. Our results demonstrate a major shift in epidemiological patterns in virus transmission, providing the first evidence that RHDV2’s ability to clinically infect young rabbits is a key competitive advantage in the field.
Recently, multiple infectious organisms have been identified as the cause of emerging diseases in lagomorphs. The most important of these emerging diseases is rabbit hemorrhagic disease virus (RHDV) type 2, a new variant with differences in pathogenicity to classical RHDV. Hepatitis E is considered an emerging zoonotic infectious disease, with widespread prevalence in many different rabbit populations. Mycobacteriosis has been recently reported in other captive domestic rabbit populations. This article provides a recent review of the published literature on emerging infectious diseases in rabbits, including farmed, laboratory, and pet rabbits, some of which have zoonotic potential.
Swamp wallabies have dramatically extended their distribution through western Victoria and south-eastern South Australia over the last 40 years. Newspaper reports from 1875 onwards show that on European settlement, wallaby populations were confined to eastern Victoria, including the ranges around Melbourne, the Otway Ranges and Portland District of south-western Victoria, and a tiny part of south-eastern South Australia. Populations contracted further with intense hunting for the fur trade until the 1930s. In the late 1970s, however, wallabies began spreading into drier habitats than those initially recorded. Possible causes underlying this change in distribution are discussed; some seem unlikely but, because wallabies began spreading soon after the introduction of European rabbit fleas as vectors of myxomatosis, the cumulative effects of releases of biological agents to control rabbits appear important. A caution is given on assuming that thick vegetation in high-rainfall areas provides the only habitat suitable for swamp wallabies, but, most importantly, the study shows how native mammals may benefit if rabbit abundance is reduced.
The southern hairy-nosed wombat (Lasiorhinus latifrons) is the faunal emblem of South Australia. It is also considered to be an agricultural pest, as its burrowing activities can cause significant damage to agricultural land and infrastructure. Unfortunately, much of our knowledge of this species' population dynamics is limited and/or out of date. The aim of this study was to estimate the distribution and abundance of southern hairy-nosed wombats in the Gawler Ranges region of South Australia, and to identify any changes since the last survey in 1988. Using a combination of satellite imagery and a ground survey conducted in May 2016, we mapped the distribution of wombat warrens in the region and counted and measured all warrens within 1000 randomly selected 1-km² cells. We estimate the current wombat population in the Gawler Ranges to be 240 095 (149 051-311 595), an increase from 14 373 in 1988. This population growth is most likely linked to a long-Term decline in the European rabbit population following the release of RHVD in the 1990s. In 2016 the IUCN upgraded the conservation status of southern hairy-nosed wombats from 'Least Concern' to 'Near Threatened'. Our findings suggest that this may not have been warranted.
Definitive diagnosis and biosecurity are fundamental steps in the control and containment of RHDV2 outbreaks, and appropriate vaccination plays a key role in this. However, the lack of pathognomonic clinical signs, limited information on the geographical prevalence of RHDV2, no or limited cross-protection for RHDV2 from vaccines against classical RHDV and difficulties in obtaining RHDV2-specific vaccines as they are manufactured outside the UK are the major constrains to disease control. Until the epidemiological situation has been clarified, it is important that vaccines against both variants are administered, especially to animals at risk or in areas where the disease is present. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved.
European rabbits (Oryctolagus cuniculus) are severely affected by rabbit haemorrhagic disease (RHD). Caused by a lagovirus, the disease leads to losses in the rabbit industry and has implications for wildlife conservation. Past RHD outbreaks have been caused by GI.1/RHDV genotype viruses. A new virus belonging to the GI.2/RHDV2/b genotype emerged in 2010, quickly spreading and replacing the former in several countries; however, limited data are available on its pathogenicity and epidemiological factors. The present work extends these issues and evaluates cross-protection between both genotypes. Ninety-four and 88 domestic rabbits were challenged with GI.2/RHDV2/b and GI.1b/RHDV variant isolates, respectively. Cross-protection was determined by a second challenge on survivors with the corresponding strain. Mortality by GI.2/RHDV2/b was highly variable due to unknown individual factors, whereas mortality by GI.1b/RHDV was associated with age. Mortality in rabbits < 4 weeks old was 84%, higher than previously reported. Cross-protection was not identical between the two viruses because the ratio of mortality rate ratios for the first and second challenges was 3.80 ± 2.68 times higher for GI.2/RHDV2/b than it was for GI.1b/RHDV. Rabbit susceptibility to GI.2/RHDV2/b varied greatly and appeared to be modulated by the innate functionality of the immune response and/or its prompt activation by other pathogens. GI.1b/RHDV pathogenicity appeared to be associated with undetermined age-related factors. These results suggest that GI.2/RHDV2/b may interact with other pathogens at the population level but does not satisfactorily explain the GI.1b/RHDV virus's quick replacement.
Rabbit haemorrhagic disease (RHD) is a highly infectious, often fatal, disease of rabbits and it is commonly found throughout the UK. RHD is caused by rabbit haemorrhagic disease virus (RHDV), also known as rabbit calicivirus (RCV). Since 2010, a new virus variant (RHDV2/RHDVb) emerged in Europe, and was identified in the UK in 2014; this new variant has now replaced the original virus in many countries. This article discusses the diagnosis and prevention of RHDV2 and the resources, such as diagnostic laboratories and vaccines, currently available in the UK.
The Rabbit Haemorrhagic Disease Virus (RHDV) was imported into Australia in 1995 as a biocontrol agent to manage one of the most successful and devastating invasive species, the European rabbit (Oryctolagus cuniculus). During the first disease outbreaks, RHDV caused mortality rates of up to 97% and reduced Australian rabbit numbers to very low levels. However, recently increased genetic resistance to RHDV and strong population growth has been reported. Major histocompatibility complex (MHC) class I immune genes are important for immune responses against viruses, and a high MHC variability is thought to be crucial in adaptive processes under pathogen-driven selection. We asked whether strong population bottlenecks and presumed genetic drift would have led to low MHC variability in wild Australian rabbits, and if the retained MHC variability was enough to explain the increased resistance against RHD. Despite the past bottlenecks we found a relatively high number of MHC class I sequences distributed over 2-4 loci. We identified positive selection on putative antigen-binding sites of the MHC. We detected evidence for RHDV-driven selection as one MHC supertype was negatively associated with RHD survival, fitting expectations of frequency-dependent selection. Gene duplication and pathogen-driven selection are possible (and likely) mechanisms that maintained the adaptive potential of MHC genes in Australian rabbits. Our findings not only contribute to a better understanding of the evolution of invasive species, they are also important in the light of planned future rabbit biocontrol in Australia.
Emergent diseases may alter the structure and functioning of ecosystems by creating new biotic interactions and modifying existing ones, producing cascading processes along trophic webs. Recently, a new variant of the rabbit haemorrhagic disease virus (RHDV2 or RHDVb) arguably caused widespread declines in a keystone prey in Mediterranean ecosystems - the European rabbit (Oryctolagus cuniculus). We quantitatively assess the impact of RHDV2 on natural rabbit populations and in two endangered apex predator populations: the Iberian lynx (Lynx pardinus) and the Spanish Imperial eagle (Aquila adalberti). We found 60–70% declines in rabbit populations, followed by decreases of 65.7% in Iberian lynx and 45.5% in Spanish Imperial eagle fecundities. A revision of the web of trophic interactions among rabbits and their dependent predators suggests that RHDV2 acts as a keystone species, and may steer Mediterranean ecosystems to management-dependent alternative states, dominated by simplified mesopredator communities. This model system stresses the importance of diseases as functional players in the dynamics of trophic webs.
The arrival of a new variant of rabbit haemorrhagic disease virus, known as RHDV2, has recently taken place in the native range of the European rabbit (Oryctolagus cuniculus), a keystone species which has undergone a sharp decline over the last sixty years as a consequence of certain harmful factors. Several works have noted the presence of this new variant in wild rabbit populations, and have in some cases recorded high mortality rates. However, little is known about the response to the arrival of this new virus variant at the population level. The goal of this work is therefore to show recent trends in 26 wild rabbit populations between 2010 (before the outbreak of the disease) and 2014 (after its onset) in two different ecosystems (woodland and agricultural areas), in order to test how their abundances changed over this period, which coincided with the spread of the RHDV2. Overall, our results showed that rabbit abundance was much lower in 2014 than in 2010, and that only 11.5% of the populations monitored proved to have a positive trend, that is, a higher abundance in 2014 than 2010. A positive correlation between rabbit abundance in 2010 and rabbit population trends was obtained, thus suggesting that the impact of the new variant on rabbit abundance is less evident in high density populations. Our results suggest that smaller rabbit populations are those most vulnerable to the outbreak of RHDV 2 and are therefore likely to decline sharply or even become extinct
To the Editor: In May 2015 an isolate of the recently emerged variant of rabbit hemorrhagic disease virus (RHDV), RHDV2, was identified in an Australian wild rabbit (Oryctolagus cuniculus). RHDV2 (also called RHDVb) was first described in outbreaks in France in 2010 (1), then Italy and Spain in 2011 (2,3) and in Portugal from 2012 onwards (4). The virus is a genetically and antigenically distinct variant of RHDV that is able to partially overcome immunity to classical strains of RHDV (1,2). In contrast to case-fatality rates for other strains of RHDV, those for RHDV2 infection have been reported to be lower in mature rabbits (0%–75% in 1 study, compared with >90% for classic RHDV infection) (3) but higher (50% in 1 study) in rabbit kittens as young as 30 days of age, which are normally highly resistant to lethal RHDV infection (2). RHDV2 has been reported to spread effectively in domestic rabbits in Europe (3); it may be replacing existing strains of RHDV that infect wild rabbits on the Iberian Peninsula (5), possibly because of its ability to partially overcome immunity to these strains.
In 2010 a new Lagovirus related to rabbit haemorrhagic disease virus (RHDV) emerged in France and has since rapidly spread throughout domestic and wild rabbit populations of several European countries. The new virus, termed RHDV2, exhibits distinctive genetic, antigenic and pathogenic features. Notably, RHDV2 kills rabbits previously vaccinated with RHDV vaccines. Here we report for the first time the generation and characterization of RHDV2-specific virus-like particles (VLPs). Our results further confirmed the differential antigenic properties exhibited by RHDV and RHDV2, highlighting the need of using RHDV2-specific diagnostic assays to monitor the spread of this new virus.
Context
Recovery of Australian rabbit populations from the impact of rabbit haemorrhagic disease virus (RHDV) contrasts with more prolonged suppression of wild rabbits in Europe, and has been widely discussed in the scientific community, but not yet documented in formal scientific literature. The underlying causes of recovery remain unclear, but resistance to RHDV infection has been reported in laboratory studies of wild-caught rabbits.
Aims
We document numerical changes in two South Australian wild rabbit populations that were initially suppressed by RHDV, and examine serological data to evaluate several alternative hypotheses for the cause of recovery.
Methods
Rabbit numbers were assessed from spotlight transect counts and dung mass transects between 1991 and 2011, and age and RHDV antibody sero-prevalence were estimated from rabbits shot in late summer.
Key results
Rabbit numbers were heavily suppressed by RHDV between 1995 and 2002, then increased 5- to 10-fold between 2003 and 2010. During the period of increase, annual RHDV infection rates remained stable or increased slightly, average age of rabbits remained stable and annual rainfall was below average.
Conclusions
Rabbit populations recovered but neither avoidance of RHDV infection, gradual accumulation of long-lived RHD-immune rabbits, nor high pasture productivity were contributing factors. This leaves increased annual survival from RHDV infection as the most likely cause of recovery.
Implications
Previously documented evidence of resistance to RHDV infection may be of little consequence to post-RHD recovery in rabbit numbers, unless the factors that influence the probability of infection also shape the course of infection and affect survival of infected rabbits.
The frequency and timing of rabbit haemorrhagic disease (RHD) epizootics and their impact on different age groups of rabbits were studied for 15 years in a recovering rabbit population in South Australia. We recorded the number and body size of rabbits dying during RHD epizootics, collected tissue for genetic analysis of rabbit haemorrhagic disease virus variants and compared the number of carcasses found to the number of susceptible rabbits present at the beginning of each epizootic. All RHD epizootics occurred between late winter and spring, but, progressively, epizootics started earlier and became more frequent and prolonged, fewer susceptible adult rabbits were present during epizootics, and the age of rabbits dying of RHD declined. Increased infection and virus shedding in juvenile rabbits offers the most plausible explanation for those epidemiological changes; the disease is now increasingly transmitted through populations of kittens, starting before young-of-the-year reach adult size and persisting late in the breeding season, so that most rabbits are challenged in their year of birth. These changes have increased juvenile mortality due to RHD but reduced total mortality across all age groups, because age-specific mortality rates are lower in young rabbits than in older rabbits. We hypothesise that this may be the proximate cause of recovery in rabbit populations across Australia and possibly elsewhere.
The Lagovirus rabbit hemorrhagic disease virus (RHDV), a member of the family Caliciviridae, severely affects European rabbit (Oryctolagus cuniculus) populations by causing rabbit hemorrhagic disease (RHD). RHDV is subdivided in six genogroups but, more recently, a new RHDV variant with a unique genetic and antigenic profile emerged. We performed a study in rabbits found dead in the field during 2013 and 2014 in Portugal to determine the prevalence of this new variant versus the classical RHDV. Fifty-seven liver samples were screened for the presence of RHDV and positive samples were genotyped. All cases of RHDV infection were caused by the new variant. The only former genogroup circulating in Portugal, G1, was not detected. We hence conclude that the new RHDV variant is replacing G1 in Portugal, probably due to a selective advantage. This sudden and rapid replacement emphasizes the necessity of continued monitoring of wild rabbit populations.
http://wwwnc.cdc.gov/eid/article/20/12/14-0517_article
FOLLOWING the recent letter from the AHVLA discussing the emergence of rabbit haemorrhagic disease virus variant strain 2 (RHDV-2) in England (Cornwall, Nottinghamshire, Surrey) and Wales ( VR , March 29, 2014, vol 174, p …
Since summer 2010, numerous cases of Rabbit Haemorrhagic Disease (RHD) have been reported in north-western France both in rabbitries, affecting RHD-vaccinated rabbits, and in wild populations. We demonstrate that the aetiological agent was a lagovirus phylogenetically distinct from other lagoviruses and which presents a unique antigenic profile. Experimental results show that the disease differs from RHD in terms of disease duration, mortality rates, higher occurrence of subacute/chronic forms and that partial cross-protection occurs between RHDV and the new RHDV variant, designated RHDV2. These data support the hypothesis that RHDV2 is a new member of the Lagovirus genus. A molecular epidemiology study detected RHDV2 in France a few months before the first recorded cases and revealed that one year after its discovery it had spread throughout the country and had almost replaced RHDV strains. RHDV2 was detected in continental Italy in June 2011, then four months later in Sardinia.
Rabbit haemorrhagic disease virus (RHDV), genus Lagovirus, family Caliciviridae, causes a large number of deaths in wild and domestic adult European rabbits (Oryctolagus cuniculus). The first documented outbreak dates from 1984 in China, but the virus rapidly dispersed worldwide. In 1997, an antigenic variant was detected in Italy and designated RHDVa. Despite causing symptoms similar to those caused by classic RHDV strains, marked antigenic and genetic differences exist. In some parts of Europe, RHDVa is replacing classic strains. Here, we report the presence of RHDVa on the Iberian Peninsula, where this variant was thought not to contribute to viral diversity.
A population of European rabbits (Oryctolagus cuniculus) has been monitored since November 1996 through mark-recapture as part of a longitudinal epidemiological study into two Australian rabbit biocontrol agents, rabbit haemorrhagic disease (RHD) and myxomatosis. A female rabbit, first captured as a subadult in late November 1999, was recaptured18timesbeforeits finalcaptureattheendofFebruary2007.Thelongevityofthisrabbit,beingfromitscalculated birth date to the date it was last captured, was 7.6 years. A review of the literature indicates this to be the longest lifespan recorded for a European rabbit in the wild.
An ELISA (enzyme-linked immunosorbent assay) for detecting antibodies to myxoma virus was characterised in wild rabbits for use in epidemiological studies. Virus neutralisation assays and virus challenge were used to define sera from rabbits as positive or negative for myxoma-virus antibodies. In a group of naturally infected wild rabbits, antibodies to myxoma virus were readily detectable by ELISA each month for at least 12 months in all rabbits, including those where neutralising antibodies could no longer be detected. Maternally transferred antibodies could be detected in kittens born to immune does for approximately six weeks after birth. IgM antibodies to myxoma virus were detected by ELISA only during the active disease and recovery phase of myxomatosis. The ratio of IgM : IgG at a standard serum dilution provided an index of time since infection and a confirmatory assay for early myxomatosis, because the detection of IgM corresponded approximately with the onset of clinical signs. Rabbit antibodies to the orthopoxvirus, vaccinia, did not cross-react in the ELISA.
Outbreaks of rabbit hemorrhagic disease have occurred recently in young rabbits on farms on the Iberian Peninsula where rabbits were previously vaccinated. Investigation identified a rabbit hemorrhagic disease virus variant genetically related to apathogenic rabbit caliciviruses. Improved antivirus strategies are needed to slow the spread of this pathogen.
WE wish to report the detection of a new variant of rabbit haemorrhagic disease virus (RHDV) (Lagovirus, Caliciviridae) which is circulating in France and has been causing high mortality in domestic and wild rabbit populations since the end of the summer of 2010.
Rabbit haemorrhagic disease (RHD)
Following the escape to the mainland of the rabbit hemorrhagic disease virus (RHDV) from Wardang Island off the coast of South Australia, a monitoring program was implemented over a 13 mo period, between October 1995 and October 1996 to determine the activity and rate of spread of the disease in the wild European rabbit (Oryctolagus cuniculus) population. All reports of dead rabbits were investigated. Whenever possible, liver and spleen tissue samples were collected from fresh carcasses and subsequently analysed for the presence of RHDV. Maximum rates of spread of rabbit hemorrhagic disease (RHD) in Australia ranged from 9 km/mo during summer to 414 km/mo in spring. New cases of RHD were moderate during late autumn and winter and peaked in spring. In summer the disease was rarely reported.
RABBIT haemorrhagic disease virus 2 (RHDV2) belongs to the family Caliciviridae, genus Lagovirus , along with RHDV , European brown hare syndrome virus (EBHSV) and other unassigned rabbit caliciviruses (RCVs). RHDV2 was first detected in European rabbits ( Oryctolagus cuniculus ) in France in 2010 (Le Gall-Recule and others 2011). It spread rapidly throughout Europe (Dalton and others 2012, Abrantes and others 2013, Le Gall-Recule and others 2013, Baily and others 2014, Westcott and others 2014) and was detected in Australia in May 2015 (Hall and others 2015). In contrast to RHDV and EBHSV, which are strictly species-specific and restricted to Oryctolagus (rabbit) and Lepus (hare) genera, respectively (Lavazza and others 1996), RHDV2 causes a fatal hepatitis in European rabbits (Le Gall-Recule and others 2011), Sardinian Cape hares ( Lepus capensis mediterraneus ; Puggioni and others 2013), and in Italian hares ( Lepus corsicanus ) (Camarda and others 2014). Recently, RHDV2 has also been detected in European brown hares ( Lepus europaeus ) in Italy and Spain (Velarde and others, 2016).
Australia has only two species of lagomorphs, O cuniculus and L europaeus , both introduced as game species in the mid-nineteenth century. The distribution of hares is limited to the south-east of the continent, mostly sympatric with rabbits, while rabbits inhabit an area covering 70 per cent of …
Emerging viruses are viruses that have either newly appeared in a population or have rapidly increased their range, with a corresponding increase in cases of disease. Identifiable sources of emerging viruses are usually existing viruses of animals or humans. Two emerging viruses of significance to exotic animal veterinarians are viral hemorrhagic disease virus of rabbits, and rodent-borne hantaviruses, the cause of hemorrhagic fever with renal syndrome in humans. Viral hemorrhagic disease is highly infectious and rapidly lethal and has killed large numbers of rabbits in Europe and China. It has replaced myxomatosis as the most significant viral disease of rabbits. Hantaviruses are found world-wide in many rodent hosts and are a significant source of “new” zoonoses. A rodent hantavirus was the cause of hantavirus pulmonary syndrome, which killed at least 36 people in 18 United States. Changes in natural environments, often caused by human activity, place both humans and animals in contact with previously inaccessible viruses or natural hosts. Increased international transport of rabbits and increased contact with exotic rodents carrying hantavirus are two such changes. Exotic animal veterinarians are likely to be among the first persons to see the infections and should be aware of the clinical signs and support available if they should encounter these diseases.
SUMMARY Rabbit haemorrhagic disease is a major tool for the management of introduced, wild rabbits in Australia. However, new evidence suggests that rabbits may be developing resistance to the disease. Rabbits sourced from wild populations in central and southeastern Australia, and domestic rabbits for comparison, were experimentally challenged with a low 60 ID50 oral dose of commercially available Czech CAPM 351 virus - the original strain released in Australia. Levels of resistance to infection were generally higher than for unselected domestic rabbits and also differed (0-73% infection rates) between wild populations. Resistance was lower in populations from cooler, wetter regions and also low in arid regions with the highest resistance seen within zones of moderate rainfall. These findings suggest the external influences of non-pathogenic calicivirus in cooler, wetter areas and poor recruitment in arid populations may influence the development rate of resistance in Australia.
A serological survey of 238 rabbits for antirabbit haemorrhagic disease virus (RHDV) antibodies was made in an industrial rabbitry where no signs of the disease had been reported for four years. Seroconversion was repeatedly detected and was due to a calicivirus antigenically related to RHDV but without its pathogenicity. There was a seroprevalence of 33.3 per cent among young animals at weaning at 31 days old, 27.6 per cent at five to seven days after weaning, 56.1 per cent at 13 to 14 days after weaning, 90.3 per cent at 19 to 20 days and 100 per cent at 32 to 33 days after weaning, and all the breeding rabbits were seropositive. In the last group and in the young at weaning, the anti-RHDV antibodies were mainly class IgG, but they were IgM and IgA at 13 to 14 days after weaning. In older fattening rabbits, there was a decrease of IgM and IgA and an increase of IgG confirmed seroconversion without any specific signs of rabbit haemorrhagic disease. On the basis of these results, the probable time of infection of the meat rabbits with this non-pathogenic virus was immediately after weaning.
1. Australian wild rabbits which had recovered from myxomatosis acquired in the field contained in their serum antibodies which could be detected by complement-fixation or neutralization tests for a long period (more than 18 months) after their recovery. The titre of complement-fixing antibody fell fairly rapidly during the first few months, and remained at a steady level thereafter. No change could be detected in the titre of neutralizing antibodies throughout the observation period.
2. Inoculation of such rabbits with myxoma virus was sometimes followed by the development of a local lesion at the inoculation site, and in these rabbits the titre of complement-fixing antibody rose, but there was no alteration in the neutralizing power of the serum. In other animals no lesion developed and there was no change in the antibody titre.
3. Serum was collected from a total of 824 wild rabbits from seventeen localities in eastern Australia with varying histories of myxomatosis since December 1950. Examination of 135 of these sera by both neutralization and complement-fixation tests showed that the results obtained by the two methods were in close agreement.
4. In many areas in which the disease was absent in the summer of 1950–1 and produced a violent epizootic in 1951–2, the majority (70–90 %) of the sera collected from rabbits 2–5 months after the height of the epizootic contained antibody to myxoma virus, i.e. the majority of the survivors had recovered from the disease.
5. Counts of the rabbit population before and after a violent epizootic in the summer of 1951–2, and the proportion of immune animals amongst the survivors in these areas showed that the case-mortality rate was between 99·4 and 99·8%.
6. Consideration of the results obtained in the serological surveys showed that the case-mortality rate was probably of this order (about 99·5%) in all areas in which there had been no disease or a negligible outbreak in 1950–1, whether they had a grade I or grade II kill in 1951–2.
7. In certain other areas, in which a grade I outbreak in 1950–1 was followed by a grade II or poorer kill in 1951–2, the observed immune rate was considerably higher than would be expected if the case-mortality rate (assuming that the whole rabbit population was susceptible) was 99·5%. The possible causes of this are discussed. Survival of immune survivors from the first epizootic through the second may be a factor of some importance, but it is probably not the only factor involved.
8. The areas just mentioned were exceptional. In most places there was either no build-up of population after the 1950–1 epizootic, or a second effective epizootic destroyed the majority of rabbits in the small population which had developed by reproduction of the survivors of the first outbreak.
Update on rabbit haemorrhagic disease virus 2-like variant in Great Britain. The Veterinary Record 178 Disease-mediated bottom-up regulation: an emergent virus affects a keystone prey, and alters the dynamics of trophic webs
- S Choudhury
- B Monterroso
- P Garrote
- G Serronha
- A Santos
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- M Abrantes
- J Perez De Ayala
- R Silvestre
- F Carvalho
- J Vasco
- I Lopes
- A M Maio
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- M J Mills
- L S Esteves
- P J Simón
- M Á Alves
MCGOWAN, S. & CHOUDHURY, B. (2016) Update on rabbit haemorrhagic
disease virus 2-like variant in Great Britain. The Veterinary Record 178, 662–663
MONTERROSO, P., GARROTE, G., SERRONHA, A., SANTOS, E.,
DELIBES-MATEOS, M., ABRANTES, J., PEREZ DE AYALA, R., SILVESTRE, F.,
CARVALHO, J., VASCO, I., LOPES, A. M., MAIO, E., MAGALHÃES, M. J.,
MILLS, L. S., ESTEVES, P. J., SIMÓN, M. Á. & ALVES, P. C. (2016)
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prey, and alters the dynamics of trophic webs. Scientific Reports 6, 36072
Is increased juvenile infection the key to recovery of wild rabbit populations from the impact of rabbit haemorrhagic disease? Longevity record for a wild European rabbit, (Oryctolagus cuniculus) from South Australia
- G J Sinclair
- R G Peacock
- D E Capucci
- L Kovaliski
- D Sinclair
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(2014b) Is increased juvenile infection the key to recovery of wild rabbit populations from the impact of rabbit haemorrhagic disease? European Journal of Wildlife
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rabbit, (Oryctolagus cuniculus) from South Australia. Australian Mammalogy 31,
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PRIMARY INDUSTRIES AND REGIONS SOUTH AUSTRALIA (PIRSA) (2016)
Confirmed and suspected RHDV2 cases in South Australia 25th August 2016.
http://www.pir.sa.gov.au/__data/assets/pdf_file/0008/272384/RHDV2_in_SA_
names.pdf Confirmed 14 November 2016
PIRSA)(2016) Confirmed and suspected RHDV2 cases in South Australia 25th
- Primary
- South Australia