The Experts below are selected from a list of 1383 Experts worldwide ranked by ideXlab platform
Anthony R Fooks - One of the best experts on this subject based on the ideXlab platform.
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current rabies vaccines do not confer protective immunity against divergent Lyssaviruses circulating in europe
2019Co-Authors: Juan Emilio Echevarria, Lorraine M Mcelhinney, Anthony R Fooks, Ashley C. BanyardAbstract:The use of the rabies vaccine for post-exposure prophylaxis started as early as 1885, revealing a safe and efficient tool to prevent human rabies cases. Preventive vaccination is the basis for the control of canine-mediated rabies, which has already been eliminated from extensive parts of the world, including Europe. Plans to eliminate canine-mediated human rabies by 2030 have been agreed upon by international organisations. However, rabies vaccines are not efficacious against some divergent Lyssaviruses. The presence in European indigenous bats of recently described Lyssaviruses, which are not neutralised by antibody responses to existing vaccines, as well as the declaration of an imported case of an African lyssavirus, which also escapes vaccine-derived protection, leaves the European health authorities unable to provide efficacious protective vaccines to some potential situations of human exposure. All these circumstances highlight the need for a universal pan-lyssavirus rabies vaccine, able to prevent human rabies in all circumstances.
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Bats and Viruses: Emergence of Novel Lyssaviruses and Association of Bats with Viral Zoonoses in the EU
2019Co-Authors: Rebecca Shipley, Anthony R Fooks, Edward Wright, David Selden, J. N. Aegerter, Ashley C. BanyardAbstract:Bats in the EU have been associated with several zoonotic viral pathogens of significance to both human and animal health. Virus discovery continues to expand the existing understating of virus classification, and the increased interest in bats globally as reservoirs or carriers of zoonotic agents has fuelled the continued detection and characterisation of new Lyssaviruses and other viral zoonoses. Although the transmission of Lyssaviruses from bat species to humans or terrestrial species appears rare, interest in these viruses remains, through their ability to cause the invariably fatal encephalitis—rabies. The association of bats with other viral zoonoses is also of great interest. Much of the EU is free of terrestrial rabies, but several bat species harbor Lyssaviruses that remain a risk to human and animal health. Whilst the rabies virus is the main cause of rabies globally, novel related viruses continue to be discovered, predominantly in bat populations, that are of interest purely through their classification within the lyssavirus genus alongside the rabies virus. Although the rabies virus is principally transmitted from the bite of infected dogs, these related Lyssaviruses are primarily transmitted to humans and terrestrial carnivores by bats. Even though reports of zoonotic viruses from bats within the EU are rare, to protect human and animal health, it is important characterise novel bat viruses for several reasons, namely: (i) to investigate the mechanisms for the maintenance, potential routes of transmission, and resulting clinical signs, if any, in their natural hosts; (ii) to investigate the ability of existing vaccines, where available, to protect against these viruses; (iii) to evaluate the potential for spill over and onward transmission of viral pathogens in novel terrestrial hosts. This review is an update on the current situation regarding zoonotic virus discovery within bats in the EU, and provides details of potential future mechanisms to control the threat from these deadly pathogens.
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rabies and the Lyssaviruses
2019Co-Authors: Anthony R Fooks, Ashley C. BanyardAbstract:Abstract Rabies is one of most ancient and feared viral pathogens with productive infection causing an invariably fatal encephalitis responsible for over 59,000 human deaths annually. Rabies is zoonotic being transmitted to humans in almost all cases through the bite of an infected dog. The virus is highly neurotropic and replication in the central nervous system represents a key barrier to treatment. A multifaceted approach for human rabies eradication that involves government support, disease awareness, vaccination of at-risk human populations and, most importantly, dog rabies control, is necessary to achieve the WHO goal of eliminating dog-mediated human rabies by 2030.
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the lyssavirus host specificity conundrum rabies virus the exception not the rule
2018Co-Authors: Denise A Marston, Conrad Martin Freuling, Stefan Finke, Lorraine M Mcelhinney, Anthony R Fooks, Thomas Müller, Ashley C. Banyard, Xavier De LamballerieAbstract:Lyssaviruses are a diverse range of viruses which all cause the disease rabies. Of the 16 recognized species, only rabies viruses (RABV) have multiple host reservoirs. Although Lyssaviruses are capable of infecting all mammals, onward transmission in a new host population requires adaptation of the virus, in a number of stages with both host and virus factors determining the outcome. Due to an absence of recorded non-RABV host shifts, RABV data is extrapolated to draw conclusions for all Lyssaviruses. In this article, we have focused on evidence of host shifts in the same insectivorous bat reservoir species in North America (RABV) and Europe (EBLV-1, EBLV-2 and BBLV). How RABV has successfully crossed species barriers and established infectious cycles in new hosts to be the global multi-host pathogen it is today, whilst other Lyssaviruses appear restricted in host species is explored in this review. It hypothesized that RABV is the exception, rather than the rule, in this fascinating genus of viruses.
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Complete Genome Sequence of Lleida Bat Lyssavirus.
2017Co-Authors: Denise A Marston, Conrad Martin Freuling, Lorraine M Mcelhinney, Thomas Müller, Ashley C. Banyard, Richard J. Ellis, Emma L. Wise, Xavier De Lamballerie, Nidia Aréchiga-ceballos, Anthony R FooksAbstract:All Lyssaviruses (family Rhabdoviridae) cause the disease rabies, an acute progressive encephalitis for which, once symptoms occur, there is no effective cure. Using next-generation sequencing, the full-genome sequence for a novel lyssavirus, Lleida bat lyssavirus (LLEBV), from the original brain of a common bent-winged bat has been confirmed.
Lorraine M Mcelhinney - One of the best experts on this subject based on the ideXlab platform.
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current rabies vaccines do not confer protective immunity against divergent Lyssaviruses circulating in europe
2019Co-Authors: Juan Emilio Echevarria, Lorraine M Mcelhinney, Anthony R Fooks, Ashley C. BanyardAbstract:The use of the rabies vaccine for post-exposure prophylaxis started as early as 1885, revealing a safe and efficient tool to prevent human rabies cases. Preventive vaccination is the basis for the control of canine-mediated rabies, which has already been eliminated from extensive parts of the world, including Europe. Plans to eliminate canine-mediated human rabies by 2030 have been agreed upon by international organisations. However, rabies vaccines are not efficacious against some divergent Lyssaviruses. The presence in European indigenous bats of recently described Lyssaviruses, which are not neutralised by antibody responses to existing vaccines, as well as the declaration of an imported case of an African lyssavirus, which also escapes vaccine-derived protection, leaves the European health authorities unable to provide efficacious protective vaccines to some potential situations of human exposure. All these circumstances highlight the need for a universal pan-lyssavirus rabies vaccine, able to prevent human rabies in all circumstances.
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the lyssavirus host specificity conundrum rabies virus the exception not the rule
2018Co-Authors: Denise A Marston, Conrad Martin Freuling, Stefan Finke, Lorraine M Mcelhinney, Anthony R Fooks, Thomas Müller, Ashley C. Banyard, Xavier De LamballerieAbstract:Lyssaviruses are a diverse range of viruses which all cause the disease rabies. Of the 16 recognized species, only rabies viruses (RABV) have multiple host reservoirs. Although Lyssaviruses are capable of infecting all mammals, onward transmission in a new host population requires adaptation of the virus, in a number of stages with both host and virus factors determining the outcome. Due to an absence of recorded non-RABV host shifts, RABV data is extrapolated to draw conclusions for all Lyssaviruses. In this article, we have focused on evidence of host shifts in the same insectivorous bat reservoir species in North America (RABV) and Europe (EBLV-1, EBLV-2 and BBLV). How RABV has successfully crossed species barriers and established infectious cycles in new hosts to be the global multi-host pathogen it is today, whilst other Lyssaviruses appear restricted in host species is explored in this review. It hypothesized that RABV is the exception, rather than the rule, in this fascinating genus of viruses.
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Complete Genome Sequence of Lleida Bat Lyssavirus.
2017Co-Authors: Denise A Marston, Conrad Martin Freuling, Lorraine M Mcelhinney, Thomas Müller, Ashley C. Banyard, Richard J. Ellis, Emma L. Wise, Xavier De Lamballerie, Nidia Aréchiga-ceballos, Anthony R FooksAbstract:All Lyssaviruses (family Rhabdoviridae) cause the disease rabies, an acute progressive encephalitis for which, once symptoms occur, there is no effective cure. Using next-generation sequencing, the full-genome sequence for a novel lyssavirus, Lleida bat lyssavirus (LLEBV), from the original brain of a common bent-winged bat has been confirmed.
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Sanger Sequencing of Lyssaviruses
2014Co-Authors: Lorraine M Mcelhinney, Conrad Martin Freuling, Denise A Marston, Thomas Müller, Richard J. Ellis, Anthony R FooksAbstract:Sanger dideoxy terminator sequencing was developed by Fred Sanger and colleagues in 1977 and became the most widely used method for virus characterization in the last three decades. More recently, Sanger sequencing has been supplanted by Next-Generation Sequencing (NGS) methods, for the determination of viral genomes. However, the Sanger method continues to be employed for the sequencing of lyssavirus polymerase chain reaction (PCR) products to facilitate virus typing, molecular epidemiological, or evolutionary studies. Sequencing overlapping PCR products (or “Walking the Genome”) by the Sanger method may still be cost effective for small-scale virus genome studies. This chapter outlines the protocols employed to prepare and sequence lyssavirus PCR products by the Sanger method.
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next generation sequencing of Lyssaviruses
2014Co-Authors: Denise A Marston, Conrad Martin Freuling, Lorraine M Mcelhinney, Anthony R Fooks, Thomas Müller, Richard J. Ellis, Emma L. WiseAbstract:With the advent of Next Generation Sequencing (NGS) technologies, the ability to quickly generate large amounts of sequence data has revolutionized the genomics field. Most RNA viruses have relatively small genomes in comparison to other organisms and as such, would be expected to easily generate genome sequence data via NGS technologies. However, due to the relatively low abundance of viral RNA in relation to host RNA, RNA viruses have proved relatively difficult to sequence using NGS technologies. Here, we detail a simple, robust methodology, without the use of ultra-centrifugation, filtration or viral enrichment protocols, to prepare RNA from diagnostic clinical tissue samples, cell monolayers and tissue culture supernatant, for subsequent sequencing on the Roche 454 platform.
Charles E. Rupprecht - One of the best experts on this subject based on the ideXlab platform.
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update on Lyssaviruses and rabies will past progress play as prologue in the near term towards future elimination
2020Co-Authors: Rodney E Rohde, Charles E. RupprechtAbstract:Rabies is an ancient, much-feared, and neglected infectious disease. Caused by pathogens in the family Rhabdoviridae, genus Lyssavirus, and distributed globally, this viral zoonosis results in tens of thousands of human fatalities and millions of exposures annually. All mammals are believed susceptible, but only certain taxa act as reservoirs. Dependence upon direct routing to, replication within, and passage from the central nervous system serves as a basic viral strategy for perpetuation. By a combination of stealth and subversion, Lyssaviruses are quintessential neurotropic agents and cause an acute, progressive encephalitis. No treatment exists, so prevention is the key. Although not a disease considered for eradication, something of a modern rebirth has been occurring within the field as of late with regard to detection, prevention, and management as well as applied research. For example, within the past decade, new Lyssaviruses have been characterized; sensitive and specific diagnostics have been optimized; pure, potent, safe, and efficacious human biologics have improved human prophylaxis; regional efforts have controlled canine rabies by mass immunization; wildlife rabies has been controlled by oral rabies vaccination over large geographic areas in Europe and North America; and debate has resumed over the controversial topic of therapy. Based upon such progress to date, there are certain expectations for the next 10 years. These include pathogen discovery, to uncover additional Lyssaviruses in the Old World; laboratory-based surveillance enhancement by simplified, rapid testing; anti-viral drug appearance, based upon an improved appreciation of viral pathobiology and host response; and improvements to canine rabies elimination regionally throughout Africa, Asia, and the Americas by application of the best technical, organizational, economic, and socio-political practices. Significantly, anticipated Gavi support will enable improved access of human rabies vaccines in lesser developed countries at a national level, with integrated bite management, dose-sparing regimens, and a 1 week vaccination schedule.
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rabies and related Lyssaviruses
2018Co-Authors: Charles E. Rupprecht, Rachel ChikwambaAbstract:Rabies is a significant neglected vaccine-preventable disease that is global in distribution. Multiple biologics are utilized in routine prevention and control of this zoonosis. Currently, rabies vaccines are used to interrupt a productive viral encephalitis before or after pathogen exposure in humans and animals. In addition, rabies immune globulins are used as part of prophylaxis after human exposure to a known or suspect animal. Such rabid animals are diagnosed based upon antigenic detection in the brain by selective antibody conjugates. Although experimental proof of concept has been demonstrated in a variety of systems, to date no plant-produced biologics have been licensed for such applications in rabies surveillance, prevention or control. In addition, given the breadth of the host spectrum, there are multiple domestic and wild mammalian species that lack specific vaccines and the cross reactivity of existing products is limited by considerable viral diversity. Hence, if safe, effective and inexpensive biologics may be produced in plants, especially for oral delivery, there is a considerable global niche to fill within the realms of public health, veterinary medicine and conservation biology.
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antigenic typing of Lyssaviruses by monoclonal antibodies
2015Co-Authors: Maria Luiza Carrieri, Ivanete Kotait, Charles E. RupprechtAbstract:The application of monoclonal antibodies (MAbs) to antigenic typing of rabies virus (RABV) and, subsequently, its differentiation from other members of the Lyssavirus genus, was one of the most important developments in the applied research related to epidemiological laboratory-based surveillance of the disease at the end of the 1970s. This chapter describes the primary methods used for antigenic characterization and their application, mainly in developing countries.
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Development of a mouse monoclonal antibody cocktail for post-exposure rabies prophylaxis in humans.
2009Co-Authors: Thomas Müller, Conrad Martin Freuling, Christine Fehlner-gardiner, Anthony R Fooks, Bernhard Dietzschold, Hildegund Ertl, Jeannette Kliemt, Francois X. Meslin, Franka Richard, Charles E. RupprechtAbstract:As the demand for rabies post-exposure prophylaxis (PEP) treatments has increased exponentially in recent years, the limited supply of human and equine rabies immunoglobulin (HRIG and ERIG) has failed to provide the required passive immune component in PEP in countries where canine rabies is endemic. Replacement of HRIG and ERIG with a potentially cheaper and efficacious alternative biological for treatment of rabies in humans, therefore, remains a high priority. In this study, we set out to assess a mouse monoclonal antibody (MoMAb) cocktail with the ultimate goal to develop a product at the lowest possible cost that can be used in developing countries as a replacement for RIG in PEP. Five MoMAbs, E559.9.14, 1112-1, 62-71-3, M727-5-1, and M777-16-3, were selected from available panels based on stringent criteria, such as biological activity, neutralizing potency, binding specificity, spectrum of neutralization of Lyssaviruses, and history of each hybridoma. Four of these MoMAbs recognize epitopes in antigenic site II and one recognizes an epitope in antigenic site III on the rabies virus (RABV) glycoprotein, as determined by nucleotide sequence analysis of the glycoprotein gene of unique MoMAb neutralization-escape mutants. The MoMAbs were produced under Good Laboratory Practice (GLP) conditions. Unique combinations (cocktails) were prepared, using different concentrations of the MoMAbs that were capable of targeting non-overlapping epitopes of antigenic sites II and III. Blind in vitro efficacy studies showed the MoMab cocktails neutralized a broad spectrum of Lyssaviruses except for Lyssaviruses belonging to phylogroups II and III. In vivo, MoMAb cocktails resulted in protection as a component of PEP that was comparable to HRIG. In conclusion, all three novel combinations of MoMAbs were shown to have equal efficacy to HRIG and therefore could be considered a potentially less expensive alternative biological agent for use in PEP and prevention of rabies in humans.
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epidemiology and pathogenicity of african bat Lyssaviruses
2008Co-Authors: Wanda Markotter, Florence Cliquet, Claude T Sabeta, Anthony R Fooks, Charles E. Rupprecht, Ivan V. Kuzmin, Janusz T Paweska, C Van Eeden, Robert Swanepoel, Louis Hendrik NelAbstract:Lyssaviruses belonging to all four known African Lyssavirus genotypes (gts) have been reported and isolated from SouthAfrica over the past few decades. These are: (1) Duvenhage virus (gt4), isolated again in 2006 from a human fatality; (2) Mokola virus (gt3), isolated irregularly, mostly from cats; (3) Lagos bat virus (gt2) continually isolated over the past four years from Epomophorus fruit bats and from incidental terrestrial animals and (4) Rabies virus (gt1) - with two virus biotypes endemic in mongoose and in canid species (mostly domestic dogs, jackals and bat-eared foxes), respectively. Only two of these are associated with bats in Southern Africa, viz. Duvenhage virus and Lagos bat virus (gts 4 and 2). For both these genotypes the authors have embarked on a programme of comparative study of molecular epidemiology. Duvenhage virus nucleoprotein nucleotide sequence analysis indicated a very low nucleotide diversity even though isolates were isolated decades apart. In contrast, individual isolates of Lagos bat virus were found to differ significantly with respectto nucleoprotein gene nucleotide sequence diversity as well as in pathogenicity profiles.
Noël Tordo - One of the best experts on this subject based on the ideXlab platform.
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molecular epidemiology of Lyssaviruses in eurasia
2008Co-Authors: Lorraine M Mcelhinney, Noël Tordo, Denise A Marston, Thomas Müller, Nicholas Johnson, S Stankov, C Black, Yong Jiang, A R FooksAbstract:The Lyssavirus genus, a member of the Rhabdoviridae family, consists of seven established related viruses (genotypes 1-7). Rabies cases in Eurasia are principally attributed to three of these genotypes, namely genotype 1 (RABV, classical rabies) and to a lesser extent genotypes 5 and 6 (European bat Lyssaviruses type-1 and -2). In addition, four newly identified divergent Lyssaviruses have been isolated from insectivorous bats. The molecular diversity of classical rabies viruses (genotype 1, RABV) has been studied at the global level and reference has been made to the existence of a number of European strains in a range of mammalian species. It is accepted that these viruses cluster within a 'Cosmopolitan Lineage' having ancestral roots in Europe in the 17th century before its widespread dispersal to Asia, Africa and the Americas as a result of European exploration and colonization.
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interaction of Lyssaviruses with the low affinity nerve growth factor receptor p75ntr
2001Co-Authors: Christine Tuffereau, Noël Tordo, Corinne Jallet, Emmanuel Desmezieres, Jacqueline Benejean, Anne Flamand, Pierre PerrinAbstract:The low-affinity nerve-growth factor receptor p75NTR interacts in vitro with the rabies virus (RV) glycoprotein and serves as a receptor for RV. The Lyssavirus genus comprises seven genotypes (GTs) of rabies and rabies-related viruses. The ability of p75NTR to interact with the glycoprotein of representative Lyssaviruses from each GT was investigated. This investigation was based on a specific binding assay between BSR cells infected with a lyssavirus and Spodoptera frugiperda (Sf21) cells expressing p75NTR on the cell surface. A specific interaction was observed with the glycoprotein of GT 1 RV (challenge virus standard or Pasteur virus strains) as well as wild-type RV and the glycoprotein of GT 6 European bat lyssavirus type 2. In contrast, no interaction was detected with the glycoprotein of Lyssaviruses of GTs 2–5 and 7. Therefore, p75NTR is only a receptor for some lyssavirus glycoproteins, indicating that the other GTs must use an alternative specific receptor.
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host switching in lyssavirus history from the chiroptera to the carnivora orders
2001Co-Authors: Hassan Badrane, Noël TordoAbstract:Lyssaviruses are unsegmented RNA viruses causing rabies. Their vectors belong to the Carnivora and Chiroptera orders. We studied 36 carnivoran and 17 chiropteran Lyssaviruses representing the main genotypes and variants. We compared their genes encoding the surface glycoprotein, which is responsible for receptor recognition and membrane fusion. The glycoprotein is the main protecting antigen and bears virulence determinants. Point mutation is the main force in lyssavirus evolution, as Sawyer's test and phylogenetic analysis showed no evidence of recombination. Tests of neutrality indicated a neutral model of evolution, also supported by globally high ratios of synonymous substitutions (d(S)) to nonsynonymous substitutions (d(N)) (>7). Relative-rate tests suggested similar rates of evolution for all lyssavirus lineages. Therefore, the absence of recombination and similar evolutionary rates make phylogeny-based conclusions reliable. Phylogenetic reconstruction strongly supported the hypothesis that host switching occurred in the history of Lyssaviruses. Indeed, Lyssaviruses evolved in chiropters long before the emergence of carnivoran rabies, very likely following spillovers from bats. Using dated isolates, the average rate of evolution was estimated to be roughly 4.3 x 10(-4) d(S)/site/year. Consequently, the emergence of carnivoran rabies from chiropteran Lyssaviruses was determined to have occurred 888 to 1,459 years ago. Glycoprotein segments accumulating more d(N) than d(S) were distinctly detected in carnivoran and chiropteran Lyssaviruses. They may have contributed to the adaptation of the virus to the two distinct mammal orders. In carnivoran Lyssaviruses they overlapped the main antigenic sites, II and III, whereas in chiropteran Lyssaviruses they were located in regions of unknown functions.
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production and neurotropism of lentivirus vectors pseudotyped with lyssavirus envelope glycoproteins
2001Co-Authors: Nathalie Desmaris, Christine Salaun, Caroline Petit, Marie-christine Prévost, Olivier Schwartz, Hugues De Rocquigny, Pierre Perrin, Assumpció Bosch, Noël Tordo, Jean Michel HeardAbstract:Abstract We investigated the production efficiency and the gene transfer capacity in the central nervous system of HIV-1-based vectors pseudotyped with either the G protein of the Mokola Lyssaviruses (MK-G), a neurotropic virus causing rabies disease, or the vesiculo-stomatitis G protein (VSV-G). Both envelopes induced syncitia in cell cultures. They were incorporated into vector particles and mature virions were observed by electron microscopy. Vector production was two- to sixfold more efficient with VSV-G than with MK-G. For equivalent amounts of physical particles, vector titration was 5- to 25-fold higher with VSV-G than with MK-G pseudotypes on cultured cells, and in vivo gene expression in mouse brain was more intense. Thus, VSV-G pseudotypes were produced more efficiently and were more infectious than MK-G pseudotypes. Tropism for brain cells was analyzed by intrastriatal injections in rats. Both pseudotypes preferentially transduced neurons (70–90% of transduced cells). Retrograde axonal transport was investigated by instilling vector suspensions in the rat nasal cavity. Both pseudotypes were efficiently transported to olfactive neuron bodies. Thus, although coating HIV-1 particles with rabdhovirus envelope glycoproteins enables them to enter neuronal cells efficiently, pseudotyping is not sufficient to confer the powerful neurotropism of Lyssaviruses to lentivirus vectors.
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cytoplasmic dynein lc8 interacts with lyssavirus phosphoprotein
2000Co-Authors: Yves Jacob, Hassan Badrane, Pierreemmanuel Ceccaldi, Noël TordoAbstract:Using a yeast two-hybrid human brain cDNA library screen, the cytoplasmic dynein light chain (LC8), a 10-kDa protein, was found to interact strongly with the phosphoprotein (P) of two Lyssaviruses: rabies virus (genotype 1) and Mokola virus (genotype 3). The high degree of sequence divergence between these P proteins (only 46% amino acid identity) favors the hypothesis that this interaction is a common property shared by all Lyssaviruses. The P protein-dynein LC8 interaction was confirmed by colocalization with laser confocal microscopy in infected cells and by coimmunoprecipitation. The dynein-interacting P protein domain was mapped to the 186 amino acid residues of the N-terminal half of the protein. Dynein LC8 is a component of both cytoplasmic dynein and myosin V, which are involved in a wide range of intracellular motile events, such as microtubule minus-end directed organelle transport in axon “retrograde transport” and actin-based vesicle transport, respectively. Our results provide support for a model of viral nucleocapsid axoplasmic transport. Furthermore, the role of LC8 in cellular mechanisms other than transport, e.g., inhibition of neuronal nitric oxide synthase, suggests that the P protein interactions could be involved in physiopathological mechanisms of rabies virus-induced pathogenesis.
Ashley C. Banyard - One of the best experts on this subject based on the ideXlab platform.
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current rabies vaccines do not confer protective immunity against divergent Lyssaviruses circulating in europe
2019Co-Authors: Juan Emilio Echevarria, Lorraine M Mcelhinney, Anthony R Fooks, Ashley C. BanyardAbstract:The use of the rabies vaccine for post-exposure prophylaxis started as early as 1885, revealing a safe and efficient tool to prevent human rabies cases. Preventive vaccination is the basis for the control of canine-mediated rabies, which has already been eliminated from extensive parts of the world, including Europe. Plans to eliminate canine-mediated human rabies by 2030 have been agreed upon by international organisations. However, rabies vaccines are not efficacious against some divergent Lyssaviruses. The presence in European indigenous bats of recently described Lyssaviruses, which are not neutralised by antibody responses to existing vaccines, as well as the declaration of an imported case of an African lyssavirus, which also escapes vaccine-derived protection, leaves the European health authorities unable to provide efficacious protective vaccines to some potential situations of human exposure. All these circumstances highlight the need for a universal pan-lyssavirus rabies vaccine, able to prevent human rabies in all circumstances.
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Bats and Viruses: Emergence of Novel Lyssaviruses and Association of Bats with Viral Zoonoses in the EU
2019Co-Authors: Rebecca Shipley, Anthony R Fooks, Edward Wright, David Selden, J. N. Aegerter, Ashley C. BanyardAbstract:Bats in the EU have been associated with several zoonotic viral pathogens of significance to both human and animal health. Virus discovery continues to expand the existing understating of virus classification, and the increased interest in bats globally as reservoirs or carriers of zoonotic agents has fuelled the continued detection and characterisation of new Lyssaviruses and other viral zoonoses. Although the transmission of Lyssaviruses from bat species to humans or terrestrial species appears rare, interest in these viruses remains, through their ability to cause the invariably fatal encephalitis—rabies. The association of bats with other viral zoonoses is also of great interest. Much of the EU is free of terrestrial rabies, but several bat species harbor Lyssaviruses that remain a risk to human and animal health. Whilst the rabies virus is the main cause of rabies globally, novel related viruses continue to be discovered, predominantly in bat populations, that are of interest purely through their classification within the lyssavirus genus alongside the rabies virus. Although the rabies virus is principally transmitted from the bite of infected dogs, these related Lyssaviruses are primarily transmitted to humans and terrestrial carnivores by bats. Even though reports of zoonotic viruses from bats within the EU are rare, to protect human and animal health, it is important characterise novel bat viruses for several reasons, namely: (i) to investigate the mechanisms for the maintenance, potential routes of transmission, and resulting clinical signs, if any, in their natural hosts; (ii) to investigate the ability of existing vaccines, where available, to protect against these viruses; (iii) to evaluate the potential for spill over and onward transmission of viral pathogens in novel terrestrial hosts. This review is an update on the current situation regarding zoonotic virus discovery within bats in the EU, and provides details of potential future mechanisms to control the threat from these deadly pathogens.
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rabies and the Lyssaviruses
2019Co-Authors: Anthony R Fooks, Ashley C. BanyardAbstract:Abstract Rabies is one of most ancient and feared viral pathogens with productive infection causing an invariably fatal encephalitis responsible for over 59,000 human deaths annually. Rabies is zoonotic being transmitted to humans in almost all cases through the bite of an infected dog. The virus is highly neurotropic and replication in the central nervous system represents a key barrier to treatment. A multifaceted approach for human rabies eradication that involves government support, disease awareness, vaccination of at-risk human populations and, most importantly, dog rabies control, is necessary to achieve the WHO goal of eliminating dog-mediated human rabies by 2030.
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the lyssavirus host specificity conundrum rabies virus the exception not the rule
2018Co-Authors: Denise A Marston, Conrad Martin Freuling, Stefan Finke, Lorraine M Mcelhinney, Anthony R Fooks, Thomas Müller, Ashley C. Banyard, Xavier De LamballerieAbstract:Lyssaviruses are a diverse range of viruses which all cause the disease rabies. Of the 16 recognized species, only rabies viruses (RABV) have multiple host reservoirs. Although Lyssaviruses are capable of infecting all mammals, onward transmission in a new host population requires adaptation of the virus, in a number of stages with both host and virus factors determining the outcome. Due to an absence of recorded non-RABV host shifts, RABV data is extrapolated to draw conclusions for all Lyssaviruses. In this article, we have focused on evidence of host shifts in the same insectivorous bat reservoir species in North America (RABV) and Europe (EBLV-1, EBLV-2 and BBLV). How RABV has successfully crossed species barriers and established infectious cycles in new hosts to be the global multi-host pathogen it is today, whilst other Lyssaviruses appear restricted in host species is explored in this review. It hypothesized that RABV is the exception, rather than the rule, in this fascinating genus of viruses.
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Complete Genome Sequence of Lleida Bat Lyssavirus.
2017Co-Authors: Denise A Marston, Conrad Martin Freuling, Lorraine M Mcelhinney, Thomas Müller, Ashley C. Banyard, Richard J. Ellis, Emma L. Wise, Xavier De Lamballerie, Nidia Aréchiga-ceballos, Anthony R FooksAbstract:All Lyssaviruses (family Rhabdoviridae) cause the disease rabies, an acute progressive encephalitis for which, once symptoms occur, there is no effective cure. Using next-generation sequencing, the full-genome sequence for a novel lyssavirus, Lleida bat lyssavirus (LLEBV), from the original brain of a common bent-winged bat has been confirmed.
