Rainer G Ulrich

Friedrich Loeffler Institute, Griefswald, Mecklenburg-Vorpommern, Germany

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Publications (178)503.19 Total impact

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    ABSTRACT: Rats are known as reservoirs and vectors for several zoonotic pathogens. However, information on the viruses shed by urban wild rats that could pose zoonotic risk to human health is scare. Here, intestinal contents from 20 wild Norway rats (Rattus norvegicus) collected in the city of Berlin, Germany, were subjected to metagenomic analysis of viral nucleic acids. The determined faecal viromes of rats consisted of a variety of known and unknown viruses and were highly variable among the individuals. Members of the families Parvoviridae and Picobirnaviridae represented the most abundant species. Novel picorna-, boca-, sapo- and stool-associated circular ssDNA viruses (SCV) were identified, which showed only low sequence identities to known representatives of the corresponding taxa. In addition, noro- and rotaviruses were detected as potential zoonotic gastroenteritis viruses. However, partial genome sequence analyses indicated that the norovirus was closely related to the recently identified rat norovirus and the rotavirus B was closely related to the rat rotavirus strain IDIR; both viruses clustered separately from respective human virus strains in phylogenetic trees. In contrast, the rotavirus A sequences showed high identities to human and animal strains. Analysis of the nearly complete genome of this virus revealed the known genotypes G3, P[3] and N2 for three of the genome segments, whereas the remaining eight genome segments represented the novel genotypes I20-R11-C11-M10-A22-T14-E18-H13. In conclusion, the results indicate a high heterogeneity of enteric viruses present in urban wild rats; their ability to be transmitted to humans remains to be assessed in future.
    Journal of General Virology 08/2014; · 3.13 Impact Factor
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    ABSTRACT: The hepatitis E virus (HEV) was first identified in 1990, although hepatitis E-like diseases in humans have been recorded for a long time dating back to the 18th century. The HEV genotypes 1 to 4 have been subsequently detected in human hepatitis E cases with different geographical distribution and different modes of transmission. Genotypes 3 and 4 have been identified in parallel in pigs, wild boars and other animal species and their zoonotic potential has been confirmed. Until 2010, these genotypes along with avian HEV strains infecting chicken were the only known representatives of the familiy Hepeviridae. Thereafter, additional HEV-related viruses have been detected in wild boars, distinct HEV-like viruses were identified in rats, rabbit, ferret, mink, fox, bats and moose, and a distantly related agent was described from closely related salmonid fish. This review summarizes the characteristics of the so far known HEV-like viruses, their phylogenetic relationship, host association and proposed involvement in diseases. Based on the reviewed knowledge, a suggestion for a new taxonomic grouping scheme of the viruses within the family Hepeviridae is presented.
    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 07/2014; · 3.22 Impact Factor
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    ABSTRACT: Abstract Rodents are important reservoirs for a large number of zoonotic pathogens. We examined the occurrence of 11 viral, bacterial, and parasitic agents in rodent populations in Austria, including three different hantaviruses, lymphocytic choriomeningitis virus, orthopox virus, Leptospira spp., Borrelia spp., Rickettsia spp., Bartonella spp., Coxiella burnetii, and Toxoplasma gondii. In 2008, 110 rodents of four species (40 Clethrionomys glareolus, 29 Apodemus flavicollis, 26 Apodemus sylvaticus, and 15 Microtus arvalis) were trapped at two rural sites in Lower Austria. Chest cavity fluid and samples of lung, spleen, kidney, liver, brain, and ear pinna skin were collected. We screened selected tissue samples for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, Leptospira, Borrelia, Rickettsia, Bartonella spp., C. burnetii, and T. gondii by RT-PCR/PCR and detected nucleic acids of Tula hantavirus, Leptospira spp., Borrelia afzelii, Rickettsia spp., and different Bartonella species. Serological investigations were performed for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, and Rickettsia spp. Here, Dobrava-Belgrade hantavirus-, Tula hantavirus-, lymphocytic choriomeningitis virus-, orthopox virus-, and rickettsia-specific antibodies were demonstrated. Puumala hantavirus, C. burnetii, and T. gondii were neither detected by RT-PCR/PCR nor by serological methods. In addition, multiple infections with up to three pathogens were shown in nine animals of three rodent species from different trapping sites. In conclusion, these results show that rodents in Austria may host multiple zoonotic pathogens. Our observation raises important questions regarding the interactions of different pathogens in the host, the countermeasures of the host's immune system, the impact of the host-pathogen interaction on the fitness of the host, and the spread of infectious agents among wild rodents and from those to other animals or humans.
    Vector borne and zoonotic diseases (Larchmont, N.Y.) 06/2014; · 2.61 Impact Factor
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    ABSTRACT: In Germany, rabies in bats is a notifiable zoonotic disease, which is caused by European bat lyssaviruses type 1 and 2 (EBLV-1 and 2), and the recently discovered new lyssavirus species Bokeloh bat lyssavirus (BBLV). As the understanding of bat rabies in insectivorous bat species is limited, in addition to routine bat rabies diagnosis, an enhanced passive surveillance study, i.e. the retrospective investigation of dead bats that had not been tested for rabies, was initiated in 1998 to study the distribution, abundance and epidemiology of lyssavirus infections in bats from Germany. A total number of 5478 individuals representing 21 bat species within two families were included in this study. The Noctule bat (Nyctalus noctula) and the Common pipistrelle (Pipistrellus pipistrellus) represented the most specimens submitted. Of all investigated bats, 1.17% tested positive for lyssaviruses using the fluorescent antibody test (FAT). The vast majority of positive cases was identified as EBLV-1, predominately associated with the Serotine bat (Eptesicus serotinus). However, rabies cases in other species, i.e. Nathusius' pipistrelle bat (Pipistrellus nathusii), P. pipistrellus and Brown long-eared bat (Plecotus auritus) were also characterized as EBLV-1. In contrast, EBLV-2 was isolated from three Daubenton's bats (Myotis daubentonii). These three cases contribute significantly to the understanding of EBLV-2 infections in Germany as only one case had been reported prior to this study. This enhanced passive surveillance indicated that besides known reservoir species, further bat species are affected by lyssavirus infections. Given the increasing diversity of lyssaviruses and bats as reservoir host species worldwide, lyssavirus positive specimens, i.e. both bat and virus need to be confirmed by molecular techniques.
    PLoS Neglected Tropical Diseases 05/2014; 8(5):e2835. · 4.57 Impact Factor
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    J Jacob, R G Ulrich, J Freise, E Schmolz
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    ABSTRACT: Rodents can harbor and transmit pathogens that can cause severe disease in humans, companion animals and livestock. Such zoonotic pathogens comprise more than two thirds of the currently known human pathogens. The epidemiology of some zoonotic pathogens, such as hantaviruses, can be linked to the population dynamics of the rodent host. In this case, during an outbreak of the rodent host population many human infections may occur. In other rodent-borne zoonotic diseases such phenomena are not known and in many cases the rodent host specificity of a given pathogen is unclear. The monitoring of relevant rodent populations and of the rodent-borne zoonotic pathogens is essential to (1) understand the distribution and epidemiology of pathogens and (2) develop forecasting tools to predict outbreaks of zoonoses. Presently, there are no systematic long-term monitoring programs in place for zoonoses in Germany. Rodent monitoring activities are largely restricted to the plant protection sector, such as for the common vole (Microtus arvalis) and forest-damaging rodents. However, during the last 10-15 years a number of specific research projects have been initiated and run for a few years and Norway rat (Rattus norvegicus) monitoring has been implemented in Hamburg and Lower Saxony. Based on close cooperation of federal and state authorities and research institutions these efforts could be utilized to gain information about the distribution and importance of rodent-borne zoonoses. Nevertheless, for the integration of rodent population dynamics and zoonotic disease patterns and especially for developing predictive models, long-term monitoring is urgently required. To establish a systematic long-term monitoring program, existing networks and cooperation need to be used, additional collaborators (e.g., pest control operators) should be included and synergetic effects of different scientific fields should be utilized.
    Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz 05/2014; 57(5):511-518. · 0.72 Impact Factor
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    ABSTRACT: An increase in acute autochthonous hepatitis E virus (HEV) infections has been recorded in Germany. These are suspected to be zoonotically transmitted from wild boar, deer and domestic pig. The latter may represent a major reservoir for HEV. In this study, 537 sera from humans living in Westphalia and Lower Saxony, representing areas of high pig density in Germany, were tested for the presence of HEV-specific antibodies. Among them were 302 individuals with occupational, direct contact to pigs and 235 individuals without direct contact to pigs. Two commercial tests and one in-house assay were applied for the detection of HEV-specific immunoglobulin G (IgG) antibodies. Sera were also tested in an assay that detects all classes of HEV-specific antibodies. Depending on the test used, the seroprevalence ranged from 4.1 to 27.9 %. Exposition to pigs was found to be associated with a significantly higher seroprevalence in subjects with contact to pigs (13.2-32.8 %) compared with that in non-exposed humans (7.7-21.7 %). In particular, individuals younger than 40 years with occupational exposure exhibited a markedly higher HEV seroprevalence compared with non-exposed individuals of that age group. In general, HEV seroprevalence increased with age resulting in a similar prevalence level in the age group of ≥50 years for exposed and non-exposed individuals. Analysis of all sera by a commercial anti-HEV IgM ELISA revealed 35 positive and 25 borderline samples. However, only one positive serum could be confirmed by an IgM line assay. Selected samples from IgM and/or IgG as well as total HEV antibody-positive individuals were also tested for the presence of HEV RNA. In one of the 78 samples, the only IgM ELISA positive and IgM line assay confirmed sample, RNA of HEV genotype 3 was detected. This sequence has high similarity to HEV sequences obtained from wild boars and domestic pigs from Germany and The Netherlands. This study demonstrates that in addition to the consumption of raw or undercooked meat, direct contact to pigs has to be considered as an additional risk factor for HEV infection.
    Medical Microbiology and Immunology 04/2014; · 3.55 Impact Factor
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    ABSTRACT: A 21-year-old male patient from Borna, Saxony, in Eastern Germany, suffered from acute kidney injury (AKI) and symptoms typical for a hantavirus infection. These symptoms included nausea, vomiting, abdominal pain, diarrhea, and acute renal failure. Serological investigations by indirect IgM and IgG in-house ELISAs, commercial immunofluorescence and line assays, as well as chemiluminescence focus reduction neutralization assay confirmed an acute Dobrava-Belgrade virus (DOBV) infection of the patient. Serological and RT-PCR analyses of striped field mouse (Apodemus agrarius) trapped in a neighboring region of the residence of the patient identified an infection by DOBV, genotype Kurkino. This is the first report of an autochthonous DOBV infection in a German patient living far from the known endemic region in the north of the country. This finding has implications for the awareness of physicians in areas which are not recognized as hantavirus endemic regions but where the reservoir host of the virus is present.
    Clinical nephrology 02/2014; · 1.29 Impact Factor
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    ABSTRACT: Replicative capacity of Middle East respiratory syndrome coronavirus (MERS-CoV) was assessed in cell lines derived from livestock and peridomestic small mammals on the Arabian Peninsula. Only cell lines originating from goats and camels showed efficient replication of MERS-CoV. These results provide direction in the search for the intermediate host of MERS-CoV.
    Emerging Infectious Diseases 02/2014; 20(2). · 6.79 Impact Factor
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    ABSTRACT: Abstract Few data are available on the occurrence of chlamydial infections in wild small mammals. We investigated the significance of free-living small mammals as reservoirs or transmission hosts for microorganisms of the phylum/class Chlamydiae. We obtained 3,664 tissue samples from 911 animals in Switzerland, Germany, Austria, the Czech Republic, and Afghanistan. Samples included internal organs (n = 3,652) and feces (n = 12) from 679 rodents (order Rodentia) and 232 insectivores (order Soricomorpha) and were tested by three TaqMan® real-time PCRs specific for members of the family Chlamydiaceae and selected Chlamydia-like organisms such as Parachlamydia spp. and Waddlia spp. Only one of 911 (0.11%) animals exhibited a questionable positive result by Chlamydiaceae-specific real-time PCR. Five of 911 animals (0.55%) were positive by specific real-time PCR for Parachlamydia spp. but could not be confirmed by quantitative PCR targeting the Parachlamydia acanthamoebae secY gene (secY qPCR). One of 746 animals (0.13%) was positive by real-time PCR for Waddlia chondrophila. This result was confirmed by Waddlia secY qPCR. This is the first detection of Chlamydia-like organisms in small wildlife in Switzerland. Considering previous negative results for Chlamydiaceae in wild ruminant species from Switzerland, these data suggest that wild small mammals are unlikely to be important carriers or transport hosts for Chamydiaceae and Chlamydia-like organisms.
    Journal of wildlife diseases 01/2014; · 1.27 Impact Factor
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    ABSTRACT: Members of the Dobrava-Belgrade virus (DOBV) species are hantaviruses carried by different Apodemus mice as reservoir hosts and causing hemorrhagic fever with renal syndrome (HFRS) in humans. In Central Europe, the Kurkino genotype of DOBV, associated with the striped field mouse, A. agrarius, is prevalent. This paper presents the first extensive study of the serological and molecular diagnostics, epidemiology, and clinics of DOBV-Kurkino infections in Central Europe. Serum samples from 570 German patients living in the habitat of A. agrarius (North and North-East Germany) and exhibiting febrile disease, were analysed. All samples were tested by ELISA, subsets of samples were also analysed by immunoblot, neutralisation assay, and RT-PCR. A group of 86 individuals was confirmed as DOBV-infected. The virus neutralization assay allowed a reliable identification of DOBV antibodies during both, acute and convalescent, phases of infection. However, differentiation of relevant DOBV genotypes was not possible by neutralization test but required molecular analysis. Whereas DOBV IgM antibodies tend to persist in the infected organism, RNAemia seems to be only short. Nucleotide sequences were amplified from 4 patients, and their analysis demonstrated infection by DOBV-Kurkino. With respect to the initial results, the high degree of identity of local patient- and A.agrarius-derived virus sequences may allow a closer allocation of the geographical place where the human infection occurred. In contrast to moderate/severe HFRS caused by DOBV genotypes Dobrava or Sochi, all available data showed a rather mild clinical course of HFRS due to DOBV-Kurkino infection without lethal outcomes. This article is protected by copyright. All rights reserved.
    Clinical Microbiology and Infection 01/2014; · 4.58 Impact Factor
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    Isabella Eckerle, Matthias Lenk, Rainer G Ulrich
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    ABSTRACT: Due to novel, improved and high-throughput detection methods, there is a plethora of newly identified viruses within the genus Hantavirus. Furthermore, reservoir host species are increasingly recognized besides representatives of the order Rodentia, now including members of the mammalian orders Soricomorpha/Eulipotyphla and Chiroptera. Despite the great interest created by emerging zoonotic viruses, there is still a gross lack of in vitro models, which reflect the exclusive host adaptation of most zoonotic viruses. The usually narrow host range and genetic diversity of hantaviruses make them an exciting candidate for studying virus-host interactions on a cellular level. To do so, well-characterized reservoir cell lines covering a wide range of bat, insectivore and rodent species are essential. Most currently available cell culture models display a heterologous virus-host relationship and are therefore only of limited value. Here, we review the recently established approaches to generate reservoir-derived cell culture models for the in vitro study of virus-host interactions. These successfully used model systems almost exclusively originate from bats and bat-borne viruses other than hantaviruses. Therefore we propose a parallel approach for research on rodent- and insectivore-borne hantaviruses, taking the generation of novel rodent and insectivore cell lines from wildlife species into account. These cell lines would be also valuable for studies on further rodent-borne viruses, such as orthopox- and arenaviruses.
    Viruses 01/2014; 6(3):951-67. · 2.51 Impact Factor
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    ABSTRACT: In 2009, human Dobrava-Belgrade virus (DOBV) infections were reported on the Black Sea coast of Turkey. Serologic and molecular studies of potential rodent reservoirs demonstrated DOBV infections in Apodemus flavicollis and A. uralensis mice. Phylogenetic analysis of DOBV strains showed their similarity to A. flavicollis mice-borne DOBV in Greece, Slovenia, and Slovakia.
    Emerging Infectious Diseases 01/2014; 20(1):121-5. · 6.79 Impact Factor
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    ABSTRACT: Monoclonal antibodies (MAbs) against viral glycoproteins have important diagnostic and therapeutic applications. In most cases, the MAbs specific to viral glycoproteins are raised against intact virus particles. The biosynthesis of viral glycoproteins in heterologous expression systems such as bacteria, yeast, insect or mammalian cells is often problematic due to their low expression level, improper folding and limited stability. To generate MAbs against hantavirus glycoprotein Gc, we have used initially a recombinant yeast-expressed full-length Puumala virus (PUUV) Gc protein. However, this approach was unsuccessful. As an alternative recombinant antigen, chimeric virus-like particles (VLPs) harboring a segment of PUUV Gc glycoprotein were generated in yeast Saccharomyces cerevisiae. A 99 amino acid (aa)-long segment of Gc protein was inserted into the major capsid protein VP1 of hamster polyomavirus at previously defined positions: either site #1 (aa 80-89) or site #4 (aa 280-289). The chimeric proteins were found to self-assemble to VLPs as evidenced by electron microscopy. Chimeric VLPs induced an efficient insert-specific antibody response in immunized mice. Monoclonal antibody (clone #10B8) of IgG isotype specific to hantavirus Gc glycoprotein was generated. It recognized recombinant full-length PUUV Gc glycoprotein both in ELISA and Western blot assay and reacted specifically with hantavirus-infected cells in immunofluorescence assay. Epitope mapping studies revealed the N-terminally located epitope highly conserved among different hantavirus strains. In conclusion, our approach to use chimeric VLPs was proven useful for the generation of virus-reactive MAb against hantavirus Gc glycoprotein. The generated broadly-reactive MAb #10B8 might be useful for various diagnostic applications.
    Viruses 01/2014; 6(2):640-60. · 2.51 Impact Factor
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    ABSTRACT: Hepatitis E virus (HEV) is the causative agent of acute hepatitis E in humans in developing countries, but sporadic and autochthonous cases do also occur in industrialised countries. In Europe, food-borne zoonotic transmission of genotype 3 (gt3) has been associated with domestic pig and wild boar. However, little is known about the course of HEV infection in European wild boar and their role in HEV transmission to domestic pigs. To investigate the transmissibility and pathogenesis of wild boar-derived HEVgt3, we inoculated four wild boar and four miniature pigs intravenously. Using quantitative real-time RT-PCR viral RNA was detected in serum, faeces and in liver, spleen and lymph nodes. The antibody response evolved after fourteen days post inoculation. Histopathological findings included mild to moderate lymphoplasmacytic hepatitis which was more prominent in wild boar than in miniature pigs. By immunohistochemical methods, viral antigens were detected mainly in Kupffer cells and liver sinusoidal endothelial cells, partially associated with hepatic lesions, but also in spleen and lymph nodes. While clinical symptoms were subtle and gross pathology was inconspicuous, increased liver enzyme levels in serum indicated hepatocellular injury. As the faecal-oral route is supposed to be the most likely transmission route, we included four contact animals to prove horizontal transmission. Interestingly, HEVgt3-infection was also detected in wild boar and miniature pigs kept in contact to intravenously inoculated wild boar. Given the high virus loads and long duration of viral shedding, wild boar has to be considered as an important HEV reservoir and transmission host in Europe.
    Veterinary research. 01/2014; 45(1):121.
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    ABSTRACT: Leptospirosis is an acute, febrile disease occurring in humans and animals worldwide. Leptospira spp. are usually transmitted through direct or indirect contact with the urine of infected reservoir animals. Among wildlife species, rodents act as the most important reservoir for both human and animal infection. To gain a better understanding of the occurrence and distribution of pathogenic leptospires in rodent and shrew populations in Germany, kidney specimens of 2973 animals from 11 of the 16 federal states were examined by PCR. Rodent species captured included five murine species (family Muridae), six vole species (family Cricetidae) and six shrew species (family Soricidae). The most abundantly trapped animals were representatives of the rodent species Apodemus flavicollis, Clethrionomys glareolus and Microtus agrestis. Leptospiral DNA was amplified in 10% of all animals originating from eight of the 11 federal states. The highest carrier rate was found in Microtus spp. (13%), followed by Apodemus spp. (11%) and Clethrionomys spp. (6%). The most common Leptospira genomospecies determined by duplex PCR was L. kirschneri, followed by L. interrogans and L. borgpetersenii; all identified by single locus sequence typing (SLST). Representatives of the shrew species were also carriers of Leptospira spp. In 20% of Crocidura spp. and 6% of the Sorex spp. leptospiral DNA was detected. Here, only the pathogenic genomospecies L. kirschneri was identified.
    International Journal of Environmental Research and Public Health 01/2014; 11(8):7562-74. · 2.00 Impact Factor
  • 01/2014: pages 235-292; Academic Press., ISBN: 9780124051911
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    ABSTRACT: Puumala virus (PUUV) causes mild to moderate cases of haemorrhagic fever with renal syndrome (HFRS), and is responsible for the majority of hantavirus infections of humans in Fennoscandia, Central and Western Europe. Although there are relatively many PUUV sequences available from different European countries, little is known about the presence of this virus in Poland. During population studies in 2009 a total of 45 bank voles were trapped at three sites in north-eastern Poland, namely islands on Dejguny and Dobskie Lakes and in a forest near Mikołajki. S and M segment-specific RT-PCR assays detected PUUV RNA in three animals from the Mikołajki site. The obtained partial S and M segment sequences demonstrated the highest similarity to the corresponding segments of a PUUV strain from Latvia. Analysis of chest cavity fluid samples by IgG ELISA using a yeast-expressed PUUV nucleocapsid protein resulted in the detection of two seropositive samples, both being also RT-PCR positive. Interestingly, at the trapping site in Mikołajki PUUV-positive bank voles belong to the Carpathian and Eastern genetic lineages within this species. In conclusion, we herein present the first molecular evidence for PUUV in the rodent reservoir from Poland.
    Viruses 01/2014; 6(1):340-53. · 2.51 Impact Factor
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    ABSTRACT: An increasing number of acute autochthonous human hepatitis E virus (HEV)-infections was noticed in Germany and other developed countries, most likely the result of a zoonotic virus transmission from pig, wild boar and deer. Currently there is still a lack of profound data concerning the actual prevalence of HEV-specific antibodies in domestic pig herds in Germany, in particular for regions with high pig density, and its age-dependency. 2273 domestic pig sera were collected in 2011 mainly from Bavaria, North Rhine-Westphalia and Lower Saxony from areas having a high pig density. Initially, 420 randomly selected pig sera were tested in three commercially available and in two in-house HEV-antibody ELISAs. 43.6% (183/420) to 65.5% (275/420) of the sera were demonstrated to be reactive against human pathogenic HEV genotypes 1 and/or 3. The majority of sera reacted only weakly or not at all with the rat HEV antigen with very few sera showing a stronger reactivity to this antigen compared to the genotype 3 antigen. The results of all three HEV-IgG tests, i.e. the PrioCHECK(®) HEV Ab porcine ELISA kit, the ID Screen(®) Hepatitis E Indirect Multi-species ELISA kit and the genotype 3 in-house ELISA were in good accordance. Therefore, the remaining sera were tested using the PrioCHECK(®) HEV Ab porcine ELISA kit. Samples with a borderline result were finally determined by application of the conjugate-modified recomLine HEV IgG assay. A total of 1065 of the 2273 sera (46.9%) were found to be anti-HEV IgG-positive. While 38.4% (306/796) of fatteners (age between 3 and 9 months) exhibited HEV-specific antibodies, 51.4% (759/1477) of sows (age older than 9 months) exhibited anti-HEV antibodies (P<0.001). Fatteners kept in Southern Germany had a significantly higher HEV IgG prevalence compared to fatteners kept in the high pig density federal states North Rhine-Westphalia and Lower Saxony but also in German federal states with a low pig density. In conclusion, the present study clearly demonstrates that a high percentage of domestic pigs in Germany have had contact with HEV. Seroprevalence depends on the pig's age and herd origin with the most significant regional variations for fatteners. The presence of anti-HEV-free herds may indicate that it is feasible to establish and sustain HEV-free pig herds. HEV seroprevalence still depends on the assay used for testing. This demonstrates an urgent need for test validation.
    Veterinary Microbiology 10/2013; · 3.13 Impact Factor
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    Berliner und Munchener Tierarztliche Wochenschrift 10/2013; 126(11/12):514-526.
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    ABSTRACT: The hepatitis B virus (HBV), family Hepadnaviridae, is one of most relevant human pathogens. HBV origins are enigmatic, and no zoonotic reservoirs are known. Here, we screened 3,080 specimens from 54 bat species representing 11 bat families for hepadnaviral DNA. Ten specimens (0.3%) from Panama and Gabon yielded unique hepadnaviruses in coancestral relation to HBV. Full genome sequencing allowed classification as three putative orthohepadnavirus species based on genome lengths (3,149-3,377 nt), presence of middle HBV surface and X-protein genes, and sequence distance criteria. Hepatic tropism in bats was shown by quantitative PCR and in situ hybridization. Infected livers showed histopathologic changes compatible with hepatitis. Human hepatocytes transfected with all three bat viruses cross-reacted with sera against the HBV core protein, concordant with the phylogenetic relatedness of these hepadnaviruses and HBV. One virus from Uroderma bilobatum, the tent-making bat, cross-reacted with monoclonal antibodies against the HBV antigenicity determining S domain. Up to 18.4% of bat sera contained antibodies against bat hepadnaviruses. Infectious clones were generated to study all three viruses in detail. Hepatitis D virus particles pseudotyped with surface proteins of U. bilobatum HBV, but neither of the other two viruses could infect primary human and Tupaia belangeri hepatocytes. Hepatocyte infection occurred through the human HBV receptor sodium taurocholate cotransporting polypeptide but could not be neutralized by sera from vaccinated humans. Antihepadnaviral treatment using an approved reverse transcriptase inhibitor blocked replication of all bat hepadnaviruses. Our data suggest that bats may have been ancestral sources of primate hepadnaviruses. The observed zoonotic potential might affect concepts aimed at eradicating HBV.
    Proceedings of the National Academy of Sciences 09/2013; · 9.81 Impact Factor

Publication Stats

3k Citations
503.19 Total Impact Points

Institutions

  • 2006–2014
    • Friedrich Loeffler Institute
      • • Institute for Novel and Emerging Infectious Diseases
      • • Institute of Epidemiology
      Griefswald, Mecklenburg-Vorpommern, Germany
  • 2013
    • University of Bonn - Medical Center
      Bonn, North Rhine-Westphalia, Germany
    • Justus-Liebig-Universität Gießen
      • Institut für Hygiene und Infektionskrankheiten der Tiere
      Gießen, Hesse, Germany
    • Technische Universität Dresden
      • Institut für Mikrobiologie
      Dresden, Saxony, Germany
  • 2012–2013
    • Freie Universität Berlin
      • Institute of Microbiology and Epizootics
      Berlin, Land Berlin, Germany
    • University of Bonn
      • Institute of Zoology
      Bonn, North Rhine-Westphalia, Germany
    • Christian Medical College & Hospital
      Ludhiana, Punjab, India
  • 2010–2012
    • Bundesinstitut für Risikobewertung
      • Department of Biological Safety
      Berlín, Berlin, Germany
    • Vilnius University
      • Biotechnologijos institutas
      Vilnius, Vilniaus Apskritis, Lithuania
  • 1992–2011
    • Charité Universitätsmedizin Berlin
      • • Institute of Medical Sociology
      • • Institute of Virology
      Berlin, Land Berlin, Germany
  • 2008–2010
    • Bernhard Nocht Institute for Tropical Medicine
      Hamburg, Hamburg, Germany
  • 2007–2008
    • Goethe-Universität Frankfurt am Main
      Frankfurt, Hesse, Germany
    • Universität Potsdam
      • Institute of Biochemistry and Biology
      Potsdam, Brandenburg, Germany
    • Robert Koch Institut
      Berlín, Berlin, Germany
    • Bundeswehr Institute of Microbiology
      München, Bavaria, Germany
  • 2002–2007
    • Latvian Biomedical Research and Study Centre
      Rija, Rīga, Latvia
    • Swedish Institute for Communicable Disease Control
      Tukholma, Stockholm, Sweden
    • University of Bristol
      • School of Veterinary Sciences
      Bristol, ENG, United Kingdom
    • University of Latvia
      • Biomedical Research and Study Centre
      Riga, Riga, Latvia
  • 1999–2007
    • Institute of Biotechnology Vilnius University
      Vil'nyus, Vilniaus Apskritis, Lithuania
  • 1991–2005
    • Humboldt-Universität zu Berlin
      • Department of Biology
      Berlín, Berlin, Germany
  • 2003
    • Max Planck Institute for Molecular Genetics
      Berlín, Berlin, Germany
  • 2001
    • Universität zu Lübeck
      • Department of Internal Medicine I
      Lübeck, Schleswig-Holstein, Germany
  • 2000–2001
    • Karolinska Institutet
      Solna, Stockholm, Sweden
  • 1990
    • Institute of Molecular Biology
      Mayence, Rheinland-Pfalz, Germany