A Cullinane

Irish Equine Centre, Naas, Leinster, Ireland

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Publications (23)53.22 Total impact

  • A. Cullinane
    09/2014; 26(9). DOI:10.1111/eve.12215
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    Equine Veterinary Journal 09/2014; 46(6). DOI:10.1111/evj.12302 · 2.37 Impact Factor
  • M. Ryan, S. Gildea, C. Walsh, A. Cullinane
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    ABSTRACT: Reasons for performing studyMore knowledge of equine influenza (EI) vaccine usage in training yards and the factors that influence serological response to vaccination are required to determine evidence based vaccination strategies.Objective The aim of this study was to ascertain the vaccination history of a population of Thoroughbred racehorses and identify factors that impacted on their antibody titres against EI.Study DesignObservational field study.Methods The study population consisted of 102 vaccinated Thoroughbred horses in training on a single premise. The vaccination histories recorded in their official passports were analysed. Blood samples for serological testing were collected by the veterinary surgeon one month after booster vaccination with ProteqFlu-Te™. Antibodies against EI were measured by single radial haemolysis (SRH). Multivariate statistical analysis was undertaken to determine the predictors of SRH antibody titres.ResultsThere was a strong correlation between age and number of vaccine doses received. Over 70% of horses received their first vaccine dose between 6 and 12 months of age. On average, horses had received 6 vaccine doses and the mean interval between booster vaccinations was 7.7 months. The majority of horses (95%) received more than one influenza vaccine product while 32% had received 3 vaccine products. Significantly higher antibody levels were observed in females than males and there was a significant association between the number of vaccine products administered and antibody levels. In contrast, a negative association between number of vaccine doses and SRH antibody level was demonstrated.Conclusions Important predictors of EI antibody titres in racehorses were sex, number of vaccine doses received and number of different vaccine products administered.
    Equine Veterinary Journal 09/2014; DOI:10.1111/evj.12353 · 2.37 Impact Factor
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    ABSTRACT: The efficacy of Zylexis(®), an immunomodulator in horses based on inactivated Parapoxvirus ovis (iPPVO), was assessed using an equine herpesvirus type 1 (EHV-1) challenge model in the presence of a natural infection with Streptococcus equi equi (S. equi). Eleven horses were treated with iPPVO and twelve were kept as controls. Six horses were challenged with EHV-1 and commingled with the horses on study. Animals were dosed on Days -2, 0 (just before commingling) and Day 7. On Day 11 significantly less nasal discharge, enlarged lymph nodes, EHV-1 shedding and lower rectal temperatures were observed in the iPPVO-treated group. In addition, iPPVO-treated horses showed significantly fewer enlarged lymph nodes on Days 17 and 19, significantly less lower jaw swelling on Day 3 and significantly lower rectal temperatures on Days 12 and 13. Dyspnoea, depression and anorexia were only recorded for the control group. Following challenge seven out of 11 horses in the iPPVO treated group shed EHV-1 but on Days 11, 12, 13, 14, 15 and 16 quantitative virus detection in this group was significantly lower as compared to the controls. All animals shed S. equi but the percentage of animals with positive bacterial detection was lower in the iPPVO group than in the control group from Day 14 through Day 28. This difference was significant on Day 24. No injection site reactions or adverse events were observed. In conclusion, Zylexis administration is safe and reduced clinical signs and shedding related to both EHV-1 and S. equi infections.
    Veterinary Microbiology 07/2014; 173(3-4). DOI:10.1016/j.vetmic.2014.07.015 · 2.73 Impact Factor
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    ABSTRACT: Reasons for performing studyThe protection induced by an equine influenza (EI) vaccine strain depends on its antigenic relatedness to the challenge virus. Although the World Organisation for Animal Health (OIE) recommend that both Florida sublineage clade 1 (Fc1) and clade 2 (Fc2) viruses should be included in EI vaccines, Japanese EI vaccines have not, thus far, been updated to include a Fc2 virus.Objectives To evaluate the efficacy of antibodies raised against Japanese EI vaccine strains in the neutralisation of recent Fc2 viruses.Study designAntigenic analysis.Methods Virus neutralisation tests were performed using antisera from experimentally infected horses and from horses that had received a primary course of the currently available vaccines.ResultsAntiserum raised against the Japanese EI vaccine strain A/equine/La Plata/1993, exhibited poor cross-neutralising activity against the Fc2 viruses isolated recently in Ireland and the UK which have the substitution alanine to valine at position 144 in antigenic site A of the haemagglutinin gene. In contrast the antiserum exhibited good cross-neutralising activity against the Fc2 viruses without the substitution. This finding was supported in experiments with antisera collected from vaccinated horses.Conclusions This suggests that the efficacy of the Japanese EI vaccine for some of the recent Fc2 viruses is suboptimal and that vaccines should be updated in accordance with the OIE recommendations.
    Equine Veterinary Journal 04/2014; DOI:10.1111/evj.12290 · 2.37 Impact Factor
  • A Cullinane, S Gildea, E Weldon
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    ABSTRACT: Vaccination is crucial to the control of Equine Influenza (EI). The study was conducted in an effort to lay the groundwork for achieving international harmonisation of regulatory requirements based on scientific evidence of performance of different vaccination regimes. The aim of this study was to evaluate the effectiveness of 3 different primary vaccination regimes: vaccination with the minimal intervals permitted by the racing authorities; vaccination in accordance with the manufacturer's instructions and vaccination with the longest intervals permitted by the racing authorities. Randomised, prospective clinical trial. The 55 seronegative unvaccinated horses in this study were subdivided by age and randomly allocated one of the 3 vaccination regimes. All groups were sampled each time a group was vaccinated and 3 to 5 weeks post vaccination.Horses were vaccinated with a subunit ISCOM based vaccine (Equip FT). Antibodies against EI were measured by Single Radial Haemolysis (SRH). Lengthening the vaccination intervals increased the immunity gaps between first (V1) and second (V2) doses, and V2 and third dose (V3) but did not inhibit the response to V2 and V3. The response to V2 and V3 was similar irrespective of the regime.Poor responders to V1 were identified in all age groups included in this study but the greatest number of poor responders wasamongst the yearlings. The 2- and 3-year-old horses responded better to vaccination than the weanlings or yearlings. Longer vaccination intervals permitted by racing authorities increase the periods of susceptibility to EI but they may facilitate strategic vaccination prior to times of increased risk of exposure to virus. The study provides the type of evidence based data necessary to commence meaningful discussion of international harmonisation of EI vaccination requirements.
    Equine Veterinary Journal 11/2013; 46(6). DOI:10.1111/evj.12214 · 2.37 Impact Factor
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    D Elton, A Cullinane
    Equine Veterinary Journal 11/2013; 45(6):768-769. DOI:10.1111/evj.12148 · 2.37 Impact Factor
  • A Cullinane, J R Newton
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    ABSTRACT: To date, equine influenza outbreaks have been reported all over the world with the exception of a small number of island nations including New Zealand and Iceland. Influenza is endemic in Europe and North America and is considered to be of potentially major economic significance to the equine industry worldwide. The importation of subclinically infected vaccinated horses, and inadequate quarantine procedures have resulted in several major outbreaks in susceptible populations for example, in Australia (2007) when more than 76,000 horses on over 10,000 properties were reported as infected. This review summarises the current understanding of, and recent research on, equine influenza, including epidemiology, pathogenesis, clinical characteristics, laboratory diagnosis, management and prevention. Recent advances in diagnostic techniques are discussed as are the merits of different vaccination regimes.
    Veterinary Microbiology 04/2013; DOI:10.1016/j.vetmic.2013.03.029 · 2.73 Impact Factor
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    ABSTRACT: Equine infectious anaemia virus (EIAV), the causative agent of equine infectious anaemia (EIA), possesses the least complex genomic organisation of any known extant lentivirus. Despite this relative genetic simplicity, all of the complete genomic sequences published to date are derived from just two viruses namely the North American EIAVWYOMING (EIAVWY) and the Chinese EIAVLIAONING (EIAVLIA) strains. In 2006 an outbreak of EIA occurred in Ireland apparently as a result of the importation of contaminated horse plasma from Italy and subsequent iatrogenic transmission to foals. This EIA outbreak was characterised by cases of severe, sometimes fatal disease. To begin to understand the molecular mechanisms underlying this pathogenic phenotype, complete proviral genomic sequences in the form of 12 overlapping PCR generated fragments were obtained from four of the EIAV infected animals, including two of the index cases. Sequence analysis of multiple molecular clones produced from each fragment demonstrated the extent of quasispecies diversity within individual viral genes and permitted construction of consensus whole genomic sequences for each of the four viral isolates. In addition, complete env gene sequences were obtained from eleven animals with differing clinical profiles despite exposure to a common EIAV source. Although the overall genomic organisation of the Irish EIAV isolates is typical of that seen in all other strains, the European viruses possess less than or equal to 80% nucleotide sequence identity with either EIAVWY or EIAVLIA. Furthermore, similarity plot and phylogenetic analysis suggest the Irish EIAV isolates developed independently of the North American and Chinese viruses and constitute a separate monophyletic group.
    Journal of General Virology 11/2012; DOI:10.1099/vir.0.047191-0 · 3.53 Impact Factor
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    ABSTRACT: Influenza virus infection remains a public health problem worldwide. The mechanisms underlying viral control during an uncomplicated influenza virus infection are not fully understood. Here, we developed a mathematical model including both innate and adaptive immune responses to study the within-host dynamics of equine influenza virus infection in horses. By comparing modeling predictions with both interferon and viral kinetic data, we examined the relative roles of target cell availability, and innate and adaptive immune responses in controlling the virus. Our results show that the rapid and substantial viral decline (about 2 to 4 logs within 1 day) after the peak can be explained by the killing of infected cells mediated by interferon activated cells, such as natural killer cells, during the innate immune response. After the viral load declines to a lower level, the loss of interferon-induced antiviral effect and an increased availability of target cells due to loss of the antiviral state can explain the observed short phase of viral plateau in which the viral level remains unchanged or even experiences a minor second peak in some animals. An adaptive immune response is needed in our model to explain the eventual viral clearance. This study provides a quantitative understanding of the biological factors that can explain the viral and interferon kinetics during a typical influenza virus infection.
    PLoS Computational Biology 06/2012; 8(6):e1002588. DOI:10.1371/journal.pcbi.1002588 · 4.83 Impact Factor
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    ABSTRACT: In this study, the complete genome sequences of seven equine group A rotavirus (RVA) strains (RVA/Horse-tc/GBR/L338/1991/G13P[18], RVA/Horse-wt/IRL/03V04954/2003/G3P[12] and RVA/Horse-wt/IRL/04V2024/2004/G14P[12] from Europe; RVA/Horse-wt/ARG/E30/1993/G3P[12], RVA/Horse-wt/ARG/E403/2006/G14P[12] and RVA/Horse-wt/ARG/E4040/2008/G14P[12] from Argentina; and RVA/Horse-wt/ZAF/EqRV-SA1/2006/G14P[12] from South Africa) were determined. Multiple novel genotypes were identified and genotype numbers were assigned by the Rotavirus Classification Working Group: R9 (VP1), C9 (VP2), N9 (NSP2), T12 (NSP3), E14 (NSP4), and H7 and H11 (NSP5). The genotype constellation of L338 was unique: G13-P[18]-I6-R9-C9-M6-A6-N9-T12-E14-H11. The six remaining equine RVA strains showed a largely conserved genotype constellation: G3/G14-P[12]-I2/I6-R2-C2-M3-A10-N2-T3-E2/E12-H7, which is highly divergent from other known non-equine RVA genotype constellations. Phylogenetic analyses revealed that the sequences of these equine RVA strains are related distantly to non-equine RVA strains, and that at least three lineages exist within equine RVA strains. A small number of reassortment events were observed. Interestingly, the three RVA strains from Argentina possessed the E12 genotype, whereas the three RVA strains from Ireland and South Africa possessed the E2 genotype. The unusual E12 genotype has until now only been described in Argentina among RVA strains collected from guanaco, cattle and horses, suggesting geographical isolation of this NSP4 genotype. This conserved genetic configuration of equine RVA strains could be useful for future vaccine development or improvement of currently used equine RVA vaccines.
    Journal of General Virology 12/2011; 93(Pt 4):866-75. DOI:10.1099/vir.0.039255-0 · 3.53 Impact Factor
  • S Gildea, M Quinlivan, S Arkins, A Cullinane
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    ABSTRACT: Antigenic and genetic drift of equine influenza (EI) virus is monitored annually by the Expert Surveillance Panel (ESP), which make recommendations on the need to update vaccines. Surveillance programmes are essential for this process to operate effectively and to decrease the risk of disease spread through the international movement of subclinically infected vaccinated horses. Not only is surveillance necessary to inform vaccine companies which strains are in circulation, but it serves as an early warning system for horse owners, trainers and veterinary clinicians, facilitating the implementation of appropriate prophylactic and control measures. To summarise the genetic analysis of EI viruses detected in Ireland from June 2007 to January 2010. The HA1 gene of 18 viruses was sequenced and phylogenetic analysis undertaken. All viruses belonged to the Florida sublineage of the American lineage. Clade 2 viruses predominated up to 2009. The viruses identified on 4 premises in 2007 displayed 100% nucleotide identity to A/eq/Richmond/1/07, the current clade 2 prototype. The first clade 1 virus was identified in November 2009 and, thereafter, clade 1 viruses were responsible for all the outbreaks identified. The Irish clade 1 viruses differ from the clade 1 virus responsible for the EI outbreaks in Japan and Australia in 2007. No virus of the Eurasian lineage was isolated during this surveillance period. In 2010 the ESP recommended that the vaccines should not include a H7N7 virus or a H3N8 virus of the Eurasian lineage but that they should contain both a clade 1 and clade 2 virus of the Florida sublineage. The surveillance data presented here support these recommendations and indicate that they are epidemiologically relevant. These data also serve as a scientific basis for investigating the source of epizootics and outbreaks both nationally and internationally.
    Equine Veterinary Journal 10/2011; 44(4):387-92. DOI:10.1111/j.2042-3306.2011.00472.x · 2.37 Impact Factor
  • S Gildea, S Arkins, A Cullinane
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    ABSTRACT: Outbreaks of equine influenza (EI) in endemic populations continue to cause economic loss despite widespread vaccination. To identify the key management and environmental factors that determine the risk of horses contracting EI in an endemic country and to identify control strategies. Real time-polymerase chain reaction (RT-PCR), virus isolation and haemagglutination inhibition were carried out on nasopharyngeal swabs and clotted blood samples collected from horses and ponies showing signs of respiratory disease. On premises where a diagnosis of EI was confirmed, the attending veterinary surgeon was asked to participate in an epidemiological investigation. Between June 2007 and January 2010, EI outbreaks were diagnosed on 28 premises located in 13 of the 32 counties of Ireland. Veterinary advice was sought on average more than 5 days after the first clinical signs were observed. The majority of diagnoses were made by RT-PCR. Data from 404 horses on 16 premises were used in the epidemiological analysis. In 15 premises, EI was identified following movement of horses. Housing type, teaser stallions or fomites/personnel contributed to virus spread. Vaccination status, number of years vaccination, time since last vaccination and age influenced disease expression. Isolation and vaccination were effective control measures on the premises where they were implemented. Preventative measures include: isolation, clinical monitoring, serological testing and vaccination of new arrivals, booster vaccination of horses at 6 monthly intervals, maintenance of effective boundaries between equine premises and avoidance of stabling in single air spaces. Control measures include: prompt isolation of suspected cases, rapid diagnosis by RT-PCR, booster vaccination of cohorts and implementation of biosecurity measures to avoid transmission by fomites and personnel. Implementation of these preventative and control measures should reduce the economic losses associated with outbreaks of EI.
    Equine Veterinary Journal 03/2011; 43(5):608-17. DOI:10.1111/j.2042-3306.2010.00333.x · 2.37 Impact Factor
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    ABSTRACT: Equine rhinitis viruses (ERV) cause respiratory disease and loss of performance in horses. It has been suggested that the economic significance of these viruses may have been underestimated due to insensitive methods of detection. To develop a sensitive, rapid, real-time RT-PCR (rRT-PCR) assay suitable for the routine diagnosis and epidemiological surveillance of the A and B variants of ERV. TaqMan primer probe sets for ERAV and ERBV were designed from conserved regions of the 5' UTR of the ERV genome. Over 400 samples from both clinically affected and asymptomatic horses were employed for validation of the assays. ERAV samples positive by rRT-PCR were verified by virus isolation and ERBV positive samples were verified by rRT-PCR using a different set of primers. The detection limit of the rRT-PCR for both viruses was 10-100 genome copies. Of 250 archival nasal swabs submitted for diagnostic testing over a 7 year period, 29 were ERAV positive and 3 were ERBV positive with an average incidence rate per year of 10 and 1.5%, respectively. There was evidence of co-circulation of ERAV and ERBV with equine influenza virus (EIV). Of 100 post race urine samples tested, 29 were ERAV positive by rRT-PCR. Partial sequencing of 2 ERBV positive samples demonstrated that one was 100% identical to ERBV1 from a 270 bp sequence and the other was more closely related to ERBV2 than ERBV1 (95% compared to 90% nucleotide identity in 178 bp). The rRT-PCR assays described here are specific and more sensitive than virus isolation. They have good reproducibility and are suitable for the routine diagnosis of ERAV and ERBV. These assays should be useful for investigating the temporal association between clinical signs and rhinitis virus shedding.
    Equine Veterinary Journal 03/2010; 42(2):98-104. DOI:10.2746/042516409X479559 · 2.37 Impact Factor
  • The Veterinary record 05/2009; 164(14):437. DOI:10.1136/vr.164.14.437-a · 1.63 Impact Factor
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    ABSTRACT: Three previously described NS1 mutant equine influenza viruses encoding carboxy-terminally truncated NS1 proteins are impaired in their ability to inhibit type I IFN production in vitro and are replication attenuated, and thus are candidates for use as a modified live influenza virus vaccine in the horse. One or more of these mutant viruses is safe when administered to horses, and recipient horses when challenged with wild-type influenza have reduced physiological and virological correlates of disease. Vaccination and challenge studies were done in horses, with measurement of pyrexia, clinical signs, virus shedding and systemic proinflammatory cytokines. Aerosol or intranasal inoculation of horses with the viruses produced no adverse effects. Seronegative horses inoculated with the NS1-73 and NS1-126 viruses, but not the NS1-99 virus, shed detectable virus and generated significant levels of antibodies. Following challenge with wild-type influenza, horses vaccinated with NS1-126 virus did not develop fever (>38.5 degrees C), had significantly fewer clinical signs of illness and significantly reduced quantities of virus excreted for a shorter duration post challenge compared to unvaccinated controls. Mean levels of proinflammatory cytokines IL-1beta and IL-6 were significantly higher in control animals, and were positively correlated with peak viral shedding and pyrexia on Day +2 post challenge. These data suggest that the recombinant NS1 viruses are safe and effective as modified live virus vaccines against equine influenza. This type of reverse genetics-based vaccine can be easily updated by exchanging viral surface antigens to combat the problem of antigenic drift in influenza viruses.
    Equine Veterinary Journal 01/2009; 41(1):87-92. DOI:10.2746/042516408X371937 · 2.37 Impact Factor
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    ABSTRACT: Group A rotaviruses are important causative agents of severe, acute dehydrating diarrhea in foals. A total of 86 rotavirus-positive fecal samples, collected from diarrheic foals from 11 counties in three of the four provinces of Ireland, were obtained from the Irish Equine Centre in Kildare during a 7-year (1999 to 2005) passive surveillance study and were characterized molecularly to establish the VP7 (G type) and VP4 (P type) antigenic specificities. Fifty-eight samples (67.5%) were found to contain G3 viruses, while in 26 samples (30.2%) the rotaviruses were typed as G14 and in 2 samples (2.3%) there was a mixed infection, G3 plus G14. All samples except for two, which were untypeable, were characterized as P[12]. Fifty-eight percent of the samples were obtained from County Kildare, the center of the Irish horse industry, where an apparent shift from G3P[12] to G14P[12] was observed in 2003. By sequence analysis of the VP7 protein, the G3 Irish strains were shown to resemble viruses of the G3A subtype (H2-like) (97.1 to 100% amino acid [aa] identity), while the G14 Irish strains displayed 93.9 to 97.1% aa identity to other G14 viruses. In the VP8* fragment of the VP4 protein, the P[12] Irish viruses displayed high conservation (92.3 to 100% aa) with other equine P[12] viruses. Worldwide, G3P[12] and G14P[12] are the most prevalent equine rotavirus strains, and G3P[12] vaccines have been developed for prevention of rotavirus-associated diarrhea in foals. Investigations of the VP7/VP4 diversity of the circulating equine viruses and the dynamics of strain replacement are important for better assessing the efficacies of the vaccines.
    Journal of clinical microbiology 09/2008; 46(10):3346-54. DOI:10.1128/JCM.00995-08 · 4.23 Impact Factor
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    ABSTRACT: In 2006 there was an outbreak of equine infectious anaemia (EIA) in Ireland. This paper describes the use of the diagnosis of clinical and subclinical cases of the disease. In acute cases the ELISAs and the immunoblot were more sensitive than the AGID. In one mare, fluctuating antibody levels were observed in all the serological assays before it seroconverted by AGID. Viral RNA and DNA were detected by RT-PCR and PCR in all the tissues from the infected animals examined postmortem. The PCR detected viral DNA in plasma regardless of the stage of the disease. In contrast, the RT-PCR detected RNA in only 52 per cent of the seropositive animals tested and appeared to be most sensitive for the detection of virus early in infection. Both PCR and RT-PCR demonstrated potential to detect acutely infected horses earlier than some of the official tests. The serological data suggest that the usual incubation/seroconversion period for this strain of the virus was approximately 37 days but may be more than 60 days in a few cases.
    The Veterinary record 12/2007; 161(19):647-52. DOI:10.1136/vr.161.19.647 · 1.63 Impact Factor
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    ABSTRACT: A classical limitation of early life immunization is the interference by maternally derived antibodies, which are known to inhibit the immune response to modified-live and killed vaccines. Several studies have convincingly shown that even minute amounts of maternally derived antibodies against equine influenza can strongly interfere with successful vaccination of foals born to immune mares. In this study we evaluated the response of foals born to vaccinated mares to immunization with a canarypox-vectored recombinant vaccine against equine influenza virus H3N8. The recombinant vaccine was able to efficiently prime foals in the presence of maternally derived immunity against influenza as was evidenced by a clear anamnestic antibody response when a secondary vaccination with the same vaccine was performed. The canarypox-vectored recombinant influenza vaccine therefore offers a unique opportunity to overcome the limitations of early life vaccination in the face of maternally derived immunity in foals.
    Journal of Comparative Pathology 08/2007; 137 Suppl 1:S76-80. DOI:10.1016/j.jcpa.2007.04.016 · 1.10 Impact Factor
  • M Quinlivan, R F Cook, A Cullinane
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    ABSTRACT: In 2006, an outbreak of equine infectious anaemia (EIA) occurred in Ireland. The initial source of the outbreak is believed to have been contaminated plasma imported from Italy. This paper presents the nucleotide sequence of the gag gene of the virus identified in Ireland (EIAV(Ire)), the first for a European strain of EIAV. Comparison of the gag gene with North American and Asian strains of the virus showed that the gag gene is less well conserved than previously believed, and that EIAV strains can have similar phenotypes despite considerable variations in genotype. On the basis of the deduced sequence of the EIAV(Ire) gag gene, highly sensitive, specific and quantitative RT-PCR and PCR assays were developed, and used to quantify the EIAV nucleic acid in postmortem tissues, plasma and secretions of infected horses. This is the first report of the detection and quantification of EIAV in nasal, buccal and genital swabs by RT-PCR.
    The Veterinary record 06/2007; 160(18):611-8. DOI:10.1136/vr.160.18.611 · 1.63 Impact Factor

Publication Stats

287 Citations
53.22 Total Impact Points


  • 2001–2014
    • Irish Equine Centre
      Naas, Leinster, Ireland
  • 2003
    • Dublin Institute of Technology
      • School of Biological Sciences
      Dublin, Leinster, Ireland
  • 2002
    • Gezondheidsdienst voor Dieren
      Deventer, Overijssel, Netherlands