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The hallmark of lyssavirus infection is lethal encephalomyelitis. Previous studies have reported distinct lyssavirus isolate-related differences in severity of cellular recruitment into the encephalon in a murine model of infectio...
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The hallmark of lyssavirus infection is lethal encephalomyelitis. Previous studies have reported distinct lyssavirus isolate-related differences in severity of cellular recruitment into the encephalon in a murine model of infection following peripheral inoculation with rabies virus (RABV) and European bat lyssavirus (EBLV)-1 and -2. In order to understand the role of chemokines in this process, comparative studies of the chemokine pattern, distribution and production in response to infection with these lyssaviruses were undertaken. Expression of CCL2, CCL5 and CXCL10 was observed throughout the murine brain with a distinct caudal bias in distribution, similar to both inflammatory changes and virus antigen distribution. CCL2 immunolabelling was localized to neuronal and astroglial populations. CCL5 immunolabelling was only detected in the astroglia, while CXCL10 labelling, although present in the astroglia, was more prominent in neurons. Isolate-dependent differences in the amount of chemokine immunolabelling in specific brain regions and chemokine production by neurons in vitro were observed, with a greater expression of CCL5 in vivo and CXCL10 production in vitro after EBLV infection. Additionally, strong positive associations between chemokine immunolabelling and perivascular cuffing and, to a lesser extent, virus antigen score were also observed. These differences in chemokine expression may explain the variation in severity of encephalitic changes observed in animals infected with different lyssavirus isolates
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Abstract Background Inaccurate diagnosis of encephalitis is a major issue as immunosuppressive treatments can be deleterious in case of viral infection. The European bat lyssavirus type 1 (EBLV-1), a virus related to rabies virus,...
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Abstract Background Inaccurate diagnosis of encephalitis is a major issue as immunosuppressive treatments can be deleterious in case of viral infection. The European bat lyssavirus type 1 (EBLV-1), a virus related to rabies virus, is endemic in European bats. No human case has yet been reported in Western Europe. A 59-year-old patient without specific past medical history died from encephalitis. A colony of bats lived in an outbuilding of his house. No diagnosis was made using standard procedures.Methods We used a next generation sequencing (NGS) based transcriptomic protocol to search for pathogens in autopsy samples (meninges and brain frontal lobe). Results were confirmed by polymerase chain reaction (PCR) and by antibody testing in serum. Immunochemistry was used to characterize inflammatory cells and viral antigens in brain lesions. Cells and mice were inoculated with brain extracts for virus isolation.Results The patient’s brain lesions were severe and diffuse in white and gray matter. Perivascular inflammatory infiltrates were abundant and rich in plasma cells. NGS identified European bat lyssavirus type 1a in brain, which was confirmed by PCR. A high titer of neutralizing antibodies was found in serum. No viral antigen was detected, and the virus could not be isolated by cell culture or by mouse inoculation.Conclusions The patient died from European bat lyssavirus type 1a infection. NGS was key to identifying this unexpected viral etiology in an epidemiological context that did not suggest rabies. People exposed to bats should be strongly advised to be vaccinated with rabies vaccines, which are effective against EBLV-1.
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Bat rabies cases in Europe are principally attributed to two lyssaviruses, namely European bat lyssavirus type 1 (EBLV-1) and European bat lyssavirus type 2 (EBLV-2). Between 1977 and 2011, 961 cases of bat rabies were reported to...
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Bat rabies cases in Europe are principally attributed to two lyssaviruses, namely European bat lyssavirus type 1 (EBLV-1) and European bat lyssavirus type 2 (EBLV-2). Between 1977 and 2011, 961 cases of bat rabies were reported to Rabies Bulletin Europe, with the vast majority (>97%) being attributed to EBLV-1. There have been 25 suspected cases of EBLV-2, of which 22 have been confirmed. In addition, two single isolations of unique lyssaviruses from European insectivorous bats were reported in south-west Russia in 2002 (West Caucasian bat virus) and in Germany in 2010 (Bokeloh bat lyssavirus). In this review, we present phylogenetic analyses of the EBLV-1 and EBLV-2 using partial nucleoprotein (N) gene sequences. In particular, we have analysed all EBLV-2 cases for which viral sequences (N gene, 400 nucleotides) are available (n=21). Oropharyngeal swabs collected from two healthy Myotis daubentonii during active surveillance programmes in Scotland and Switzerland also yielded viral RNA (EBLV-2). Despite the relatively low number of EBLV-2 cases, a surprisingly large amount of anomalous data has been published in the scientific literature and Genbank, which we have collated and clarified. For both viruses, geographical relationships are clearly defined on the phylogenetic analysis. Whilst there is no clear chronological clustering for either virus, there is some evidence for host specific relationships, particularly for EBLV-1 where more host variation has been observed. Further genomic regions must be studied, in particular for EBLV-1 isolates from Spain and the EBLV-2 isolates to provide support for the existence of sublineages.
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The United Kingdom has performed passive surveillance for European bat lyssaviruses (EBLVs) since 1987, and species-targeted surveillance since 2003. One critical component of these studies is the accurate identification of bats e...
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The United Kingdom has performed passive surveillance for European bat lyssaviruses (EBLVs) since 1987, and species-targeted surveillance since 2003. One critical component of these studies is the accurate identification of bats either submitted for testing or sampled in the field. Identification is dependent on numerous morphological characteristics. Whilst this is an effective means of bat identification, a number of problems remain with this approach. It relies on the experience of bat specialists and can lead to problems in differentiating members of the Myotis genus, particularly between Myotis mystacinus (whiskered bat) and Myotis brandtii (Brandt's bat), and between the most common species of the genus Pipistrellus. Furthermore, degradation of bats submitted for testing can also lead to problems in making an accurate species identification. Comparison of genetic sequence data could offer an alternative approach to differentiating bat species when morphological characterisation is not possible. Using tissue samples from UK resident bat species, sequence analysis of the mitochondrial DNA cytochrome b gene, and the β-actin gene allowed for identification of many of the most common bat species in the UK, and genetic separation of two morphologically cryptic species. Application of this approach identified the species of a bat infected with EBLV-2 in Surrey as Myotis daubentonii (Daubenton's bat).
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European bat lyssavirus 1 (EBLV-1) is a widespread lyssavirus across Europe, whose epizootic cycle is linked to a few bat species. Occasionally, EBLV-1 infection may occur in domestic animals and humans. EBLV-1 can be classified i...
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European bat lyssavirus 1 (EBLV-1) is a widespread lyssavirus across Europe, whose epizootic cycle is linked to a few bat species. Occasionally, EBLV-1 infection may occur in domestic animals and humans. EBLV-1 can be classified into two subtypes, where subtype EBLV-1a shows a wide geographic distribution between France and Russia whereas subtype EBLV-1b is distributed between Spain and Poland. In this study, we determined the genome sequence of two recent EBLV-1a strains detected in Hungary and analysed their adaptive evolution and phylodynamics. The data set that included 100 EBLV-1 genome sequences identified positive selection at selected sites in genes coding for viral proteins (N, codon 18; P, 141 and 155; G, 244 and 488; L, 168, 980, 1597 and 1754). A major genetic clade containing EBLV-1a isolates from Hungary, Slovakia, Denmark and Poland was estimated to have diverged during the 19th century whereas the divergence of the most recent ancestor of Hungarian and Slovakian isolates dates back to 1950 (time span, 1930 to 1970). Phylogeographic analysis of the EBLV-1a genomic sequences demonstrated strong evidence of viral dispersal from Poland to Hungary. This new information indicates that additional migratory flyways may help the virus spread, a finding that supplements the general theory on a west-to-east dispersal of EBLV-1a strains. Long-distance migrant bats may mediate the dispersal of EBLV-1 strains across Europe; however, structured surveillance and extended genome sequencing would be needed to better understand the epizootiology of EBLV-1 infections in Europe.
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A comparison of the clinicopathology of European bat lyssavirus (EBLV) types-1 and -2 and of rabies virus was undertaken. Following inoculation of mice at a peripheral site with these viruses, clinical signs of rabies and distribu...
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A comparison of the clinicopathology of European bat lyssavirus (EBLV) types-1 and -2 and of rabies virus was undertaken. Following inoculation of mice at a peripheral site with these viruses, clinical signs of rabies and distribution of virus antigen in the mouse brain were examined. The appearance of clinical signs of disease varied both within and across the different virus species, with variation in incubation periods and weight loss throughout disease progression. The distribution of viral antigen throughout the regions of the brain examined was similar for each of the isolates during the different stages of disease progression, suggesting that antigen distribution was not associated with clinical presentation. However, specific regions of the brain including the cerebellum, caudal medulla, hypothalamus and thalamus, showed notable differences in the proportion of virus antigen positive cells present in comparison to other brain regions suggesting that these areas are important in disease development irrespective of virus species. ? 2013.
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The first European case of bat rabies was reported in 1954. Since then, more than 800 cases have been confirmed from 13 countries. The causative agents are European Bat Lyssavirus Type-1 (EBLV-1) and Type-2 (EBLV-2). The natural h...
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The first European case of bat rabies was reported in 1954. Since then, more than 800 cases have been confirmed from 13 countries. The causative agents are European Bat Lyssavirus Type-1 (EBLV-1) and Type-2 (EBLV-2). The natural host of EBLV-1 seems to be the serotine bat (Eptesicus serotinus) with more than 95% of all cases reported in this species. Although much fewer EBLV-2 cases have been identified, it seems that Myotis dasycneme and M. daubentonii are likely to be the principal hosts' species for this virus. The ecological mechanisms underlying the transmission of EBLV-1 and EBLV-2 are still poorly understood. In order to assess the public health risks associated with EBLVs and the implications for bat conservation, some issues need urgent clarification. In this review some of the most pressing topics will be addressed. Only collaboration between a range of disciplines that include virologists, epidemiologists and bat conservationists will be able to elucidate some of these unanswered questions.
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Although classical rabies is one of the earliest identified and best studied infectious diseases, there is still limited knowledge about lyssaviruses and their major natural hosts, bats. Focussing on bat rabies in Europe caused by...
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Although classical rabies is one of the earliest identified and best studied infectious diseases, there is still limited knowledge about lyssaviruses and their major natural hosts, bats. Focussing on bat rabies in Europe caused by European bat lyssaviruses 1 (EBLV-1) and 2, for instance the association of EBLV-1 to Eptesicus bats and EBLV-2 to Myotis daubentonii and M. dasycneme together with an apparent clustering of cases is one question still to be answered. Furthermore, the question whether EBLVsare less virulent or bats less susceptible is the key to the understanding of the disease. Accumulating evidence from experimental studies and field observations, however, has resulted in contradicting hypotheses. Serological surveys, using tools developed for classical rabies, are often used for bat rabies surveillance. However, such surveys are hampered by the lack of validated methods applicable for bat sera. Bats seem to play a prominent role as reservoir for viral pathogens and the unique biologyof bats especially the immune response may contribute to this. Considering all known aspects, bat rabies seems to form a yet unsolv-able entanglement, reminiscent of the ancient tale of the Gordian knot. In this manuscript we will not be able to untanglethis knot, but we hope to offer some suggestions of where to start.
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In Europe, three genotypes of the genus Lyssavirus, family Rhabdoviridae, are present, classical rabies virus (RABV, genotype 1), European bat lyssavirus type 1 (EBLV-1, genotype 5) and European bat lyssavirus type 2 (EBLV-2, geno...
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In Europe, three genotypes of the genus Lyssavirus, family Rhabdoviridae, are present, classical rabies virus (RABV, genotype 1), European bat lyssavirus type 1 (EBLV-1, genotype 5) and European bat lyssavirus type 2 (EBLV-2, genotype 6). The entire authentic nucleoprotein (N protein) encoding sequences of RABV (challenge virus standard, CVS, strain), EBLV-1 and EBLV-2 were expressed in yeast Saccharomyces cerevisiae at high level. Purification of recombinant N proteins by caesium chloride gradient centrifugation resulted in yields between 14–17, 25–29 and 18–20 mg/l of induced yeast culture for RABV-CVS, EBLV-1 and EBLV-2, respectively. The purified N proteins were evaluated by negative staining electron microscopy, which revealed the formation of nucleocapsid-like structures. The antigenic conformation of the N proteins was investigated for their reactivity with monoclonal antibodies (mAbs) directed against different lyssaviruses. The reactivity pattern of each mAb was virtually identical between immunofluorescence assay with virus-infected cells, and ELISA and dot blot assay using the corresponding recombinant N proteins. These observations lead us to conclude that yeast-expressed lyssavirus N proteins share antigenic properties with naturally expressed virus protein. These recombinant proteins have the potential for use as components of serological assays for lyssaviruses.
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