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immune response and protection in raccoons (procyon lotor) following consumption of baits containing onrab®, a human adenovirus rabies glycoprotein recombinant vaccine.we investigated the immune response and protection conferred in raccoons (procyon lotor) following consumption of onrab(®) oral rabies vaccine baits. forty-two wild-caught, captive raccoons were each offered an onrab vaccine bait; 21 controls received no vaccine baits. blood samples collected from all raccoons before treatment, and each week posttreatment for 16 wk, were assessed for the presence of rabies virus antibody. in the bait group, an individual was considered to have responded to vacci ...201223060502
mucosal adjuvants to improve wildlife rabies vaccination.raboral v-rg(®)a is a recombinant vaccine used in oral rabies vaccination (orv) programs for wildlife in the united states. vaccination rates for raccoons are substantially lower than vaccination rates for gray foxes and coyotes. research suggests that the low viscosity of the oral vaccine may preclude animals from receiving an effective dose when biting into the vaccine bait delivery system. we evaluated the possibility of using two benign compounds, chitosan and n,n,n-trimethylated chitosan (t ...201223060506
immune clearance of attenuated rabies virus results in neuronal survival with altered gene expression.rabies virus (rabv) is a highly neurotropic pathogen that typically leads to mortality of infected animals and humans. the precise etiology of rabies neuropathogenesis is unknown, though it is hypothesized to be due either to neuronal death or dysfunction. analysis of human brains post-mortem reveals surprisingly little tissue damage and neuropathology considering the dramatic clinical symptomology, supporting the neuronal dysfunction model. however, whether or not neurons survive infection and ...201223071441
rabies virus vaccines: is there a need for a pan-lyssavirus vaccine?all members of the lyssavirus genus are capable of causing disease that invariably results in death following the development of clinical symptoms. the recent detection of several novel lyssavirus species across the globe, in different animal species, has demonstrated that the lyssavirus genus contains a greater degree of genetic and antigenic variation than previously suspected. the divergence of species within the genus has led to a differentiation of lyssavirus isolates based on both antigeni ...201223084854
complete genome sequence of a highly virulent rabies virus isolated from a rabid pig in south china.a virulent rabies virus (rabv) strain, gd-sh-01, was isolated from brain tissue of a rabid pig in china. this report describes the first complete genome sequence of a swine-origin rabv strain, and this information will provide important insights into the transmission cycle and genetic diversity of rabv from different hosts in china.201223087116
interspecies protein substitution to investigate the role of the lyssavirus glycoprotein.european bat lyssaviruses type 1 (eblv-1) and type 2 (eblv-2) circulate within bat populations throughout europe and are capable of causing disease indistinguishable from that caused by classical rabies virus (rabv). however, the determinants of viral fitness and pathogenicity are poorly understood. full-length genome clones based on the highly attenuated, non-neuroinvasive, rabv vaccine strain (sad-b19) were constructed with the glycoprotein (g) of either sad-b19 (sn), of eblv-1 (sn-1) or eblv- ...201323100360
anatomical evidence for the involvement of medial cerebellar output from the interpositus nuclei in cognitive functions.although the cerebellar interpositus nuclei are known to be involved in cognitive functions, such as associative motor learning, no anatomical evidence has been available for this issue. here we used retrograde transneuronal transport of rabies virus to identify neurons in the cerebellar nuclei that project via the thalamus to area 46 of the prefrontal cortex of macaques in comparison with the projections to the primary motor cortex (m1). after rabies injections into area 46, many neurons in the ...201223112179
addition of a single n-glycan to street rabies virus glycoprotein enhances virus production.most street rabies virus g proteins have two n-glycosylation sites, i.e. asn(37) and asn(319), whereas additional sites are found in fixed (laboratory adapted) viruses. in this study, we performed a pseudotyped virus assay using g-deficient rabies virus and demonstrated that single-n-glycan additions to the g protein of street rabies virus strain 1088, which are found in adapted strains, enhanced virus production in neural and non-neural cell lines, while additions to asn(194) or asn(247) enhanc ...201323114627
street rabies virus causes dendritic injury and f-actin depolymerization in the hippocampus.rabies is an acute viral infection of the central nervous system and is typically fatal in humans and animals; however, its pathogenesis remains poorly understood. in this study, the morphological changes of dendrites and dendritic spines in the ca1 region of the hippocampus were investigated in mice that were infected intracerebrally with an mrv strain of the street rabies virus. haematoxylin and eosin and fluorescence staining analysis of brain sections from the infected mice showed very few m ...201323114630
viral tracing of genetically defined neural circuitry.classical methods for studying neuronal circuits are fairly low throughput. transsynaptic viruses, particularly the pseudorabies (prv) and rabies virus (rabv), and more recently vesicular stomatitis virus (vsv), for studying circuitry, is becoming increasingly popular. these higher throughput methods use viruses that transmit between neurons in either the anterograde or retrograde direction. recently, a modified rabv for monosynaptic retrograde tracing was developed. (figure 1a). in this method, ...201223117695
current status of canine rabies in china.the number of human rabies cases acquired from dog bites constitutes a high proportion of the total rabies cases in china, although the number of human rabies cases has gradually decreased in recent years. the pivotal role of dogs in the spread of rabies indicates that controlling and preventing canine rabies could be a key step in eradicating human rabies in china. the primary aims of this review are to discuss the properties and pathogenesis of the rabies virus, the clinical signs and diagnosi ...201223122320
brain-targeted delivery of protein using chitosan- and rvg peptide-conjugated, pluronic-based nano-carrier.brain-targeted delivery of drug or imaging agent is hard to achieve efficiently due to the infiltrative nature of the blood-brain barrier (bbb). moreover, delivery of therapeutic proteins to brain tissue is further limited by the size and physic-chemical properties of proteins. in this work, we developed a chitosan-conjugated pluronic-based nano-carrier with a specific target peptide for the brain (rabies virus glycoprotein; rvg29) and applied for the protein delivery to the brain. the in-vivo b ...201323122677
multidisciplinary approach to epizootiology and pathogenesis of bat rabies viruses in the united states.zoonotic disease surveillance is typically initiated after an animal pathogen has caused disease in humans. early detection of potentially high-risk pathogens within animal hosts may facilitate medical interventions to cope with an emerging disease. to effectively spillover to a novel host, a pathogen may undergo genetic changes resulting in varying transmission potential in the new host and potentially to humans. rabies virus (rabv) is one model pathogen to consider for studying the dynamics of ...201323137052
desmodus rotundus and artibeus spp. bats might present distinct rabies virus lineages.in brazil, bats have been assigned an increasing importance in public health as they are important rabies reservoirs. phylogenetic studies have shown that rabies virus (rabv) strains from frugivorous bats artibeus spp. are closely associated to those from the vampire bat desmodus rotundus, but little is known about the molecular diversity of rabv in artibeus spp. the n and g genes of rabv isolated from artibeus spp. and cattle infected by d. rotundus were sequenced, and phylogenetic trees were c ...201323146155
variable evolutionary routes to host establishment across repeated rabies virus host shifts among bats.determining the genetic pathways that viruses traverse to establish in new host species is crucial to predict the outcome of cross-species transmission but poorly understood for most host-virus systems. using sequences encoding 78% of the rabies virus genome, we explored the extent, repeatability and dynamic outcome of evolution associated with multiple host shifts among new world bats. episodic bursts of positive selection were detected in several viral proteins, including regions associated wi ...201223150575
infectivity of rabies virus-exposed macrophages.rabies virus distributes widely in infected mice, including lymphoid tissues and spleen macrophages. the infection characteristics in murine macrophages and the infectivity of virus-exposed macrophages were examined upon inoculation in mice. in vitro, mf4/4 spleen macrophages supported mild virus production (10(4)-fold less than neuroblastoma), with formation of typical virions. bone marrow-derived macrophages (bmm) were most efficient to capture virus, but new virus production was not detected. ...201323159243
expression changes of cytoskeletal associated proteins in proteomic profiling of neuroblastoma cells infected with different strains of rabies virus.rabies virus invades the nervous system, induces neuronal dysfunction and causes death of the host. the disruption of the cytoskeletal integrity and synaptic structures of the neurons by rabies virus has been postulated as a possible basis for neuronal dysfunction. in the present study, a two-dimensional electrophoresis/mass spectrometry proteomics analysis of neuroblastoma cells revealed a significant effect of a virulent strain of rabies virus on the host cytoskeleton related proteins which wa ...201323168799
a ribosome-specialized translation initiation pathway is required for cap-dependent translation of vesicular stomatitis virus mrnas.initiation is the primary target of translational control for all organisms. regulation of eukaryotic translation is traditionally thought to occur through initiation factors and rna structures. here, we characterize a transcript-specific translation initiation mechanism that is mediated by the ribosome. by studying vesicular stomatitis virus (vsv), we identify the large ribosomal subunit protein rpl40 as requisite for vsv cap-dependent translation but not bulk cellular or internal ribosome entr ...201323169626
arctic-like rabies virus, bangladesh.arctic/arctic-like rabies virus group 2 spread into bangladesh ≈32 years ago. because rabies is endemic to and a major public health problem in this country, we characterized this virus group. its glycoprotein has 3 potential n-glycosylation sites that affect viral pathogenesis. diversity of rabies virus might have public health implications in bangladesh.201223171512
a new rabies vaccine based on a recombinant orf virus (parapoxvirus) expressing the rabies virus glycoprotein.the present study describes the generation of a new orf virus (orfv) recombinant, d1701-v-rabg, expressing the rabies virus (rabv) glycoprotein that is correctly presented on the surface of infected cells without the need of replication or production of infectious recombinant virus. one single immunization with recombinant orfv can stimulate high rabv-specific virus-neutralizing antibody (vna) titers in mice, cats, and dogs, representing all nonpermissive hosts for the orfv vector. the protectiv ...201223175365
rabies virus nucleoprotein expressed in silkworm pupae at high-levels and evaluation of immune responses in mice.rabies is one of the most fatal zoonotic diseases in developing countries, where a safe, cheap and effective vaccine against the disease remains unaffordable. in this paper, we describe a new silkworm-baculovirus expression system to express the nucleoprotein (n) gene of rabies virus and evaluation of the immune response in balb/c mice. a recombinant baculovirus -rbmnpv(rv-n) carrying the n gene of rabies virus evelyn rokitniki abelseth (era) strain was constructed and the n protein expression w ...201323178898
intramuscular inoculation of mice with the live-attenuated recombinant rabies virus trigas results in a transient infection of the draining lymph nodes and a robust, long-lasting protective immune response against rabies.a single intramuscular application of the live but not uv-inactivated recombinant rabies virus (rabv) variant trigas in mice induces the robust and sustained production of rabv-neutralizing antibodies that correlate with long-term protection against challenge with an otherwise lethal dose of the wild-type rabv. to obtain insight into the mechanism by which live trigas induces long-lasting protective immunity, quantitative pcr (qpcr) analysis of muscle tissue, draining lymph nodes, spleen, spinal ...201323192867
lyssavirus surveillance in bats of southern china's guangxi province.although rabies virus is widely distributed in the world, and has been the subject of extensive investigations with the objective of its ultimate prevention, control, and management, there is much less knowledge of the characteristics, distribution, and infectivity of other lyssaviruses. since bats are known animal vectors for all but one of the known lyssavirus genotypes, we have performed an extensive survey of bats in the guangxi province to provide information on lyssavirus distribution in s ...201323197137
unique characteristics of bat rabies viruses in big brown bats (eptesicus fuscus).rabies virus infection has been documented in several north american bat species, including eptesicus fuscus. the virus-host relationship between bats and rabies virus (rv) is not well understood. the incidence of non-lethal rv exposure, based on the presence of viral neutralizing antibodies, demonstrates that exposure to rv does not always lead to clinical infection in bats. it is unknown how the route of exposure, rabies virus variant, or health of the bat affects the outcome following exposur ...201323208279
human macrophage and dendritic cell-specific silencing of high-mobility group protein b1 ameliorates sepsis in a humanized mouse model.hypersecretion of cytokines by innate immune cells is thought to initiate multiple organ failure in murine models of sepsis. whether human cytokine storm also plays a similar role is not clear. here, we show that human hematopoietic cells are required to induce sepsis-induced mortality following cecal ligation and puncture (clp) in the severely immunodeficient nonobese diabetic (nod)/scid/il2rγ(-/-) mice, and sirna treatment to inhibit hmgb1 release by human macrophages and dendritic cells drama ...201223213216
isolation and identification of a novel rabies virus lineage in china with natural recombinant nucleoprotein gene.rabies virus (rabv) causes severe neurological disease and death. as an important mechanism for generating genetic diversity in viruses, homologous recombination can lead to the emergence of novel virus strains with increased virulence and changed host tropism. however, it is still unclear whether recombination plays a role in the evolution of rabv. in this study, we isolated and sequenced four circulating rabv strains in china. phylogenetic analyses identified a novel lineage of hybrid origin t ...201223226506
[immune efficacy of rabies virus glycoprotein expressed by baculovirus vector].to construct a recombinant baculovirus expressing glycoprotein (gp) of rv srv9 strain and test the immunological efficacy in mice, open reading frame of rabies virus gp gene of srv9 strain was cloned into the shuttle vector bacmid to construct the recombinant shuttle plasmid bacmid-g and transfection was performed into s f9 cells with the recombinant shuttle plasmid. cpe appeared in cell cultures was identified by electronmicroscopy. western-blot, ifa and immunity tests in mice were performed to ...201223233923
molecular characterization of kgh, the first human isolate of rabies virus in korea.the complete genome sequence of the kgh strain of the first human rabies virus, which was isolated from a skin biopsy of a patient with rabies, whose symptoms developed due to bites from a raccoon dog in 2001. the size of the kgh strain genome was determined to be 11,928 nucleotides (nt) with a leader sequence of 58 nt, nucleoprotein gene of 1,353 nt, phosphoprotein gene of 894 nt, matrix protein gene of 609 nt, glycoprotein gene of 1,575 nt, rna-dependent rna polymerase gene of 6,384 nt, and tr ...201323242520
[neuritis cordis and myocarditis in rabies].once the rabies virus has spread through the central nervous system (cns), the virus is also transported centrifugally along axons, especially of the autonomic nervous system, to a wide range of organs including the heart. in this case report of a 49-year-old man who had been bitten by a dog in asia, the rabies infection of cardiac nerves and cardiac muscle fibres is shown by immunohistochemistry. the neuritis cordis and rabies myocarditis can have important clinical effects on the heart rate an ...201323263440
phylogeography of rabies virus isolated from herbivores and bats in the espírito santo state, brazil.rabies is enzootic in the state of espírito santo, brazil. every year, cattle and horses die from rabies that is transmitted by the vampire bat desmodus rotundus. this paper describes the spread of the rabies virus by the continuous diffusion model using relaxed random walks with beast software. forty-one (41) sequences of gene g from the rabies virus that was isolated from bats and domestic herbivores from several areas of the state between 2006 and 2010 were analyzed. the phylogenetic tree sho ...201223264105
rabies virus glycoprotein is an important determinant for the induction of innate immune responses and the pathogenic mechanisms.our previous studies have suggested that street and fixed rabies viruses (rabvs) induce diseases in the mouse model via different mechanisms. in the present study, attempts were made to determine if it is the glycoprotein (g) that is responsible for the observed differences in the pathogenic mechanisms. to this end, an infectious clone from fixed virus b2c was established and used as a backbone for exchange of the g from street viruses. the rate of viral replication, expression of viral proteins ...201223265241
a novel rabies vaccine based on a recombinant parainfluenza virus 5 expressing rabies virus glycoprotein.untreated rabies virus (rabv) infection leads to death. vaccine and postexposure treatment have been effective in preventing rabv infection. however, due to cost, rabies vaccination and treatment have not been widely used in developing countries. there are 55,000 human death caused by rabies annually. an efficacious and cost-effective rabies vaccine is needed. parainfluenza virus 5 (piv5) is thought to contribute to kennel cough, and kennel cough vaccines containing live piv5 have been used in d ...201223269806
design of different strategies of multivalent dna-based vaccination against rabies and canine distemper in mice and dogs.during the vaccination campaigns, puppies younger than 3 months old are not targeted and remain unvaccinated for at least the first year of their lives. almost half of the reported rabid dogs are 6 months or younger. hence, we should recommend the vaccination against rabies of young puppies. unfortunately, owing to the exposure of puppies to infections with either canine parvovirus (cpv) or distemper virus (cdv) after the intervention of the vaccinators, owners are reluctant to vaccinate puppies ...201223270301
multisynaptic inputs from the medial temporal lobe to v4 in macaques.retrograde transsynaptic transport of rabies virus was employed to undertake the top-down projections from the medial temporal lobe (mtl) to visual area v4 of the occipitotemporal visual pathway in japanese monkeys (macaca fuscata). on day 3 after rabies injections into v4, neuronal labeling was observed prominently in the temporal lobe areas that have direct connections with v4, including area tf of the parahippocampal cortex. furthermore, conspicuous neuron labeling appeared disynaptically in ...201223272220
pathobiology of rabies virus and the european bat lyssaviruses in experimentally infected mice.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 ...201223274107
transneuronal tracing with neurotropic viruses reveals network macroarchitecture.a major challenge in systems neuroscience is to unravel the complex matrix of connections that characterize functional circuits within the central nervous system. retrograde transneuronal transport of rabies virus has proven to be especially useful for this purpose. here we provide specific examples in which transneuronal transport of rabies virus has been used to unravel multi-synaptic pathways within motor, cognitive and autonomic circuits. tracing with rabies virus defined: first, the closed- ...201323287632
spontaneous pneumomediastinum due to paralytic rabies.rabies is a fatal disease resulting from rabies virus infection, causing severe neurological symptoms and ultimately death by destroying the nervous system. in general, a patient tends to see a neurologist or an infectious diseases physician, with very common and typical discipline-related signs and symptoms, such as hydrophobia, aerophobia, and mental disorders. however, we reported a rabies patient who was first admitted to see a thoracic surgeon with spontaneous pneumomediastinum.201323290471
genetic and evolutionary characterization of rabvs from china using the phosphoprotein gene.while the function of the phosphoprotein (p) gene of the rabies virus (rabv) has been well studied in laboratory adapted rabvs, the genetic diversity and evolution characteristics of the p gene of street rabvs remain unclear. the objective of the present study was to investigate the mutation and evolution of p genes in chinese street rabvs.201323294868
oral rabies vaccination in raccoons: comparison of onrab® and raboral v-rg® vaccine-bait field performance in québec, canada and vermont, usa.the control of rabies in raccoons (procyon lotor) and striped skunks (mephitis mephitis) in north america has been conducted mainly through aerial distribution of oral vaccine-baits. the effectiveness of the vaccine-bait used is therefore of prime importance for disease eradication. in a previous field comparison between the onrab(®) bait in the province of new brunswick, canada, and raboral v-rg(®) bait in the state of maine, usa, the onrab bait produced a higher percentage of antibody-positive ...201323307388
antigenic and genetic characterization of rabies virus isolates from uruguay.after 25 years without any reported cases of rabies in uruguay, the northern region of the country experienced an epizootic of bovine paralytic rabies in october 2007. the outbreak affected bovines and equines, and the main source of infection was the bat desmodus rotundus, the only hematophagous species in the country. from october 2007 to july 2008, 42 bovine, 3 equine and 120 chiropteran samples were submitted to the national veterinary diagnostic laboratory for rabies testing. a total of 12 ...201323318595
aptamers targeting rabies virus-infected cells inhibit viral replication both in vitro and in vivo.rabies is an acute fatal encephalitis disease that affects many warm-blooded mammals. the causative agent of the disease is rabies virus (rabv). currently, no approved therapy is available once the clinical signs have appeared. aptamers, oligonucleotide ligands capable of binding a variety of molecular targets with high affinity and specificity, have recently emerged as promising therapeutic agents. in this study, sixteen high-affinity single-stranded dna (ssdna) aptamers were generated by cell- ...201323333291
kinetic studies of recombinant rabies virus glycoprotein (rvgp) cdna transcription and mrna translation in drosophila melanogaster s2 cell populations.recombinant rabies virus glycoprotein (rvgp) was expressed in cell membranes of stably transfected drosophila s2 cells using constitutive and inducible promoters. although with quantitative differences of rvgp expression in both systems, the cdna transcription, as evaluated by relative rvgp mrna levels measured by qrt-pcr, sustained the amount of rvgp producing cells and the rvgp volumetric (πrvgp) productivity. at the transition to the stationary cell growth phase, once the cell culture slowed ...201323340966
[rabies].rabies virus, a neurotropic lyssavirus responsible for unavoidable fatal encephalitis, is transmitted by saliva of infected animals through bite, scratch or licking of broken skin or a mucous membrane. infection can be prevented by timely prevention (wash for several minutes, antisepsis and vaccination completed by antirabies immunoglobulins [ig] according to the severity of exposure). the 55,000 human deaths estimated annually worldwide result mainly from uncontrolled canine rabies in enzootic ...201323351694
new modules are added to vibrissal premotor circuitry with the emergence of exploratory whisking.rodents begin to use bilaterally coordinated, rhythmic sweeping of their vibrissae ("whisking") for environmental exploration around 2 weeks after birth. whether (and how) the vibrissal control circuitry changes after birth is unknown, and the relevant premotor circuitry remains poorly characterized. using a modified rabies virus transsynaptic tracing strategy, we labeled neurons synapsing directly onto vibrissa facial motor neurons (vfmns). sources of potential excitatory, inhibitory, and modul ...201323352170
revealing the secrets of neuronal circuits with recombinant rabies virus technology.an understanding of how the brain processes information requires knowledge of the architecture of its underlying neuronal circuits, as well as insights into the relationship between architecture and physiological function. a range of sophisticated tools is needed to acquire this knowledge, and recombinant rabies virus (rabv) is becoming an increasingly important part of this essential toolbox. rabv has been recognized for years for its properties as a synapse-specific trans-neuronal tracer. a no ...201323355811
current and future approaches to the therapy of human rabies.human rabies has traditionally been considered a uniformly fatal disease. however, recent decades have seen several instances in which individuals have developed clinical signs of rabies, but survived, usually with permanent neurologic sequelae. most of these patients had received prophylactic rabies vaccine before the onset of illness. the best outcomes have been seen in patients infected with bat viruses, which appear to be less virulent for humans than strains associated with other rabies vec ...201323369672
rabies neutralizing antibody after 2 intradermal doses on days 0 and 21 for pre-exposure prophylaxis.pre-exposure prophylaxis is recommended for people who will be exposed to rabies virus in the laboratory or who will contact with mammals. world health organization recommends 2 doses of a cell-culture rabies vaccine given 1 week apart, and a third booster dose given 2-3 weeks later. neutralizing antibody response is virtually 100%, and the individual remains sensitized indefinitely. intradermal pre-exposure regimen for rabies prophylaxis is more economical compared with the conventional intramu ...201323370149
production, characterization, and antigen specificity of recombinant 62-71-3, a candidate monoclonal antibody for rabies prophylaxis in humans.rabies kills many people throughout the developing world every year. the murine monoclonal antibody (mab) 62-71-3 was recently identified for its potential application in rabies postexposure prophylaxis (pep). the purpose here was to establish a plant-based production system for a chimeric mouse-human version of mab 62-71-3, to characterize the recombinant antibody and investigate at a molecular level its interaction with rabies virus glycoprotein. chimeric 62-71-3 was successfully expressed in ...201323371065
responses of mice to inoculation with low doses of a bat rabies virus variant.rabies is generally considered a fatal disease, yet neutralizing antibodies to rabies virus (rv) have frequently been found in sera from healthy, insectivorous bats, and mark-recapture studies have demonstrated bats that are still alive years after the first detection of anti-rv antibodies. to explore this phenomenon, we exposed mice to a big brown bat variant of rv, using three routes of inoculation, two doses of virus and two frequencies of exposure. we found the highest rate of seroconversion ...201323381393
molecular evolutionary signatures reveal the role of host ecological dynamics in viral disease emergence and spread.rna viruses account for numerous emerging and perennial infectious diseases, and are characterized by rapid rates of molecular evolution. the ecological dynamics of most emerging rna viruses are still poorly understood and difficult to ascertain. the availability of genome sequence data for many rna viruses, in principle, could be used to infer ecological dynamics if changes in population numbers produced a lasting signature within the pattern of genome evolution. as a result, the rapidly emergi ...201323382419
simultaneously reconstructing viral cross-species transmission history and identifying the underlying constraints.the factors that determine the origin and fate of cross-species transmission events remain unclear for the majority of human pathogens, despite being central for the development of predictive models and assessing the efficacy of prevention strategies. here, we describe a flexible bayesian statistical framework to reconstruct virus transmission between different host species based on viral gene sequences, while simultaneously testing and estimating the contribution of several potential predictors ...201323382420
modification of the fluorescent antibody virus neutralisation test--elimination of the cytotoxic effect for the detection of rabies virus neutralising antibodies.the virus neutralisation test is used for the quantitation of specific antibodies in serum samples. however, the success of the test depends on the quality of samples. in the case of poor quality samples, a cytotoxic effect can be observed and the results of the test can be compromised. additionally, the cytotoxic effect limits the use of different substances, such as muscle extract or liquid from thoracic cavity (thoracic liquid), as a sample for the detection of rabies virus neutralising antib ...201323403247
vesicular stomatitis virus with the rabies virus glycoprotein directs retrograde transsynaptic transport among neurons in vivo.defining the connections among neurons is critical to our understanding of the structure and function of the nervous system. recombinant viruses engineered to transmit across synapses provide a powerful approach for the dissection of neuronal circuitry in vivo. we recently demonstrated that recombinant vesicular stomatitis virus (vsv) can be endowed with anterograde or retrograde transsynaptic tracing ability by providing the virus with different glycoproteins. here we extend the characterizatio ...201323403489
host-rabies virus protein-protein interactions as druggable antiviral targets.we present an unconventional approach to antiviral drug discovery, which is used to identify potent small molecules against rabies virus. first, we conceptualized viral capsid assembly as occurring via a host-catalyzed biochemical pathway, in contrast to the classical view of capsid formation by self-assembly. this suggested opportunities for antiviral intervention by targeting previously unappreciated catalytic host proteins, which were pursued. second, we hypothesized these host proteins to be ...201323404707
complete genome sequence of a rabies virus isolate from cattle in guangxi, southern china.a street rabies virus (rv) isolate, gxhxn, was obtained from brain tissue of rabid cattle in the guangxi zhuang autonomous region of china in 2009. gxhxn is the first isolate from cattle in china with its entire genome sequenced and is closely related to bj2011e from horse in beijing, wh11 from donkey in the hubei province, and isolates from dogs in the guangxi and fujian provinces, with homologies of 97.6% to 99.6%. it is more distantly related to isolates from domestic cat, pig, chinese ferret ...201323405368
development in immunoprophylaxis against rabies for animals and humans.rabies is a fatal neurological disease and a persistent global problem. it is spread primarily by domestic dogs but other canid, viverrid (skunks and raccoons) and chiropteran species are considered as the most efficient vectors of the disease. since dogs are the main perpetuator of rabies, special attention has to be given to bring all the dogs including unauthorized stray dogs under immunization umbrella in order to control rabies. vaccination is the only way to combat the disease before and a ...201023407587
reduced viral burden in paralytic compared to furious canine rabies is associated with prominent inflammation at the brainstem level.the mechanisms that differentiate rabies infections into furious and paralytic forms remain undetermined. there are no neuropathological features in human brains that distinguish furious and paralytic rabies. this could be due to methodology and/or examination of specimens late in the disease course.in this study, postmortem examination of brain (5 furious and 5 paralytic) and spinal cord (3 furious and 3 paralytic) specimens was performed in 10 rabies-infected dogs, sacrificed shortly after dev ...201323410236
relationship between virus-neutralizing antibody levels and the number of rabies vaccinations: a prospective study of dogs in japan.a mass rabies vaccination of dogs has been conducted annually in japan over the last 60 years. to assess both current levels of rabies virus-neutralizing antibody (vna) in dogs and the rationale for current vaccination procedures, we used a rapid fluorescent focus inhibition test to determine vna levels in 756 dogs that had visited animal hospitals in japan. we found that 51.1% of the dogs that had received 1 rabies vaccination had protective vna levels (≥0.5 iu/ml) with a geometric mean of 0.61 ...201323429079
the emergence of wildlife species as a source of human rabies infection in brazil.forty-five human rabies virus isolates from a wide geographical area of brazil were characterized using an anti-nucleoprotein monoclonal antibody panel and by partial nucleotide sequencing analysis of the nucleoprotein gene. three major antigenic groups related to the antigenic variants maintained in domestic dogs, vampire bats and marmosets were identified. phylogenetic analyses revealed that the viruses from dog-related cases segregated into four sister clades: three associated with dog-endemi ...201323433340
functional circuits of new neurons in the dentate gyrus.the hippocampus is crucial for memory formation. new neurons are added throughout life to the hippocampal dentate gyrus (dg), a brain area considered important for differential storage of similar experiences and contexts. to better understand the functional contribution of adult neurogenesis to pattern separation processes, we recently used a novel synapse specific trans-neuronal tracing approach to identify the (sub) cortical inputs to new dentate granule cells (gcs). it was observed that newly ...201323443839
a conceptual model for the impact of climate change on fox rabies in alaska, 1980-2010.the direct and interactive effects of climate change on host species and infectious disease dynamics are likely to initially manifest\ at latitudinal extremes. as such, alaska represents a region in the united states for introspection on climate change and disease. rabies is enzootic among arctic foxes (vulpes lagopus) throughout the northern polar region. in alaska, arctic and red foxes (vulpes vulpes) are reservoirs for rabies, with most domestic animal and wildlife cases reported from norther ...201423452510
genetic diversity and molecular evolution of the rabies virus matrix protein gene in china.to investigate the diversity of rabies virus (rabv) matrix protein (m) gene in the current chinese rabies epidemic, we fully examined m gene of 63 street rabvs (virus isolated from naturally infected animals), and performed phylogenetic and mutational analysis. our results indicate that the chinese rabv m gene is well conserved with 90.6% to 100% amino acid similarity. analysis of the mutations indicates that the sequences can be divided into four groups with each group defined by distinct subst ...201323453987
rabies virus and canine distemper virus in wild and domestic carnivores in northern kenya: are domestic dogs the reservoir?rabies virus (rv) and canine distemper virus (cdv) can cause significant mortality in wild carnivore populations, and rv threatens human lives. we investigated serological patterns of exposure to cdv and rv in domestic dogs (canis familiaris), african wild dogs (lycaon pictus), black-backed jackals (canis mesomelas), spotted hyenas (crocuta crocuta), striped hyenas (hyaena hyaena) and african lions (panthera leo), over a 10-year period, in a kenyan rangeland to assess the role domestic dogs may ...201223459924
rabies in iraq: trends in human cases 2001-2010 and characterisation of animal rabies strains from baghdad.control of rabies requires a consistent supply of dependable resources, constructive cooperation between veterinary and public health authorities, and systematic surveillance. these are challenging in any circumstances, but particularly during conflict. here we describe available human rabies surveillance data from iraq, results of renewed sampling for rabies in animals, and the first genetic characterisation of circulating rabies strains from iraq. human rabies is notifiable, with reported case ...201323469303
complete genome sequence of a street rabies virus isolated from a dog in nigeria.a canine rabies virus (rabv) was isolated from a trade dog in nigeria. its entire genome was sequenced and found to be closely related to canine rabvs circulating in africa. sequence comparison indicates that the virus is closely related to the africa 2 rabv lineage. the virus is now termed drv-ng11.201323469344
rabid fox bites and human rabies in a village community in southern india: epidemiological and laboratory investigations, management and follow-up.human rabies transmitted from wild animals is rarely reported in endemic countries like india, where nearly 95% deaths occur due to bites from rabid dogs. in this paper, we report an incidence of rabid fox bites in a village in southern part of india involving 18 individuals, including 4 children. all people had category iii exposures, including bites on the face and neck. the attacking fox was killed by the forest department and buried immediately. the victims of the fox bite did not receive ap ...201323473223
rabies virus is recognized by the nlrp3 inflammasome and activates interleukin-1β release in murine dendritic cells.inflammasome activation is important for the development of an effective host defense against many pathogens, including rna viruses. however, the mechanism by which the inflammasome recognizes rna viruses and its role in rabies virus (rabv) pathogenicity and immunogenicity remain poorly defined. to determine the function of the inflammasome in response to rabv infection, we infected murine bone marrow-derived dendritic cells (bmdcs) with rabv. our results indicate that the infection of bmdcs wit ...201323487464
retrograde monosynaptic tracing reveals the temporal evolution of inputs onto new neurons in the adult dentate gyrus and olfactory bulb.identifying the connectome of adult-generated neurons is essential for understanding how the preexisting circuitry is refined by neurogenesis. changes in the pattern of connectivity are likely to control the differentiation process of newly generated neurons and exert an important influence on their unique capacity to contribute to information processing. using a monosynaptic rabies virus-based tracing technique, we studied the evolving presynaptic connectivity of adult-generated neurons in the ...201323487772
identification of rabies virus mimotopes screened from a phage display peptide library with purified dog anti-rabies virus serum igg.the rabies virus glycoprotein (g) is a key protein for both virus infectivity and eliciting protective immunity as an antigen. what is more, the nucleoprotein (n) is also a significant rabies virus antigen. in this study, purified anti-rabies virus igg from dogs immunized with the standard cvs-11 strain was used to screen the ph.d.-12™ phage display peptide library for peptides that correspond to or mimic native g and n epitopes. in contrast to previous reports that use monoclonal antibodies or ...201323499997
isolation of irkut virus from a murina leucogaster bat in china.bats are recognized as a major reservoir of lyssaviruses; however, no bat lyssavirus has been isolated in asia except for aravan and khujand virus in central asia. all chinese lyssavirus isolates in previous reports have been of species rabies virus, mainly from dogs. following at least two recent bat-associated human rabies-like cases in northeast china, we have initiated a study of the prevalence of lyssaviruses in bats in jilin province and their public health implications. a bat lyssavirus h ...201323505588
a serum-free, purified vero cell rabies vaccine is safe and as immunogenic as the reference vaccine verorab for pre-exposure use in healthy adults: results from a randomized controlled phase-ii trial.verorab was licensed in 1985 for both pre- and post-exposure prophylaxis of rabies. the next generation purified vero cell rabies vaccine (pvrv-ng) is a highly purified vaccine. we performed a phase ii clinical study in adults in france to assess its immunological non-inferiority and clinical safety for pre-exposure prophylaxis.201323510665
internalization and fusion mechanism of vesicular stomatitis virus and related rhabdoviruses.members of the rhabdoviridae infect a wide variety of animals and plants, and are the causative agents of many important diseases. rhabdoviruses enter host cells following internalization into endosomes, with the glycoprotein (g protein) mediating both receptor binding to host cells and fusion with the cellular membrane. the recently solved crystal structure of vesicular stomatitis virus g has allowed considerable insight into the mechanism of rhabdovirus entry, in particular the low ph-dependen ...023516023
investigating the role for il-21 in rabies virus vaccine-induced immunity.over two-thirds of the world's population lives in regions where rabies is endemic, resulting in over 15 million people receiving multi-dose post-exposure prophylaxis (pep) and over 55,000 deaths per year globally. a major goal in rabies virus (rabv) research is to develop a single-dose pep that would simplify vaccination protocols, reduce costs associated with rabv prevention, and save lives. protection against rabv infections requires virus neutralizing antibodies; however, factors influencing ...201323516660
a step forward in molecular diagnostics of lyssaviruses--results of a ring trial among european laboratories.rabies is a lethal and notifiable zoonotic disease for which diagnostics have to meet the highest standards. in recent years, an evolution was especially seen in molecular diagnostics with a wide variety of different detection methods published. therefore, a first international ring trial specifically designed on the use of reverse transcription polymerase chain reaction (rt-pcr) for detection of lyssavirus genomic rna was organized. the trial focussed on assessment and comparison of the perform ...201323520505
the who rabies bulletin europe: a key source of information on rabies and a pivotal tool for surveillance and epidemiology.rabies is one of the most, if not the most, prominent and feared zoonotic diseases in the world and the world health organization (who) estimates that 55,000 people die of the disease every year. most of these deaths occur in asia and africa and are usually the result of dog-mediated rabies. in europe, the red fox is considered the main reservoir species for wildlife rabies caused by the rabies virus. besides foxes, bats have also been identified as a reservoir for european bat lyssaviruses in m ...201223520734
genetic characterization and phylogenetic analysis of skunk-associated rabies viruses in north america with special emphasis on the central plains.across north america the skunk acts as a reservoir for several rabies virus variants. some of these variants are geographically restricted in range as is the case for the california skunk variant and two distinct variants present in mexico. in contrast the north central and south central skunk rabies viruses are dispersed in overlapping ranges over large areas of the midwestern region of the united states with the former extending into southern parts of the canadian prairies. despite this extens ...201323524137
complete genome and molecular epidemiological data infer the maintenance of rabies among kudu (tragelaphus strepsiceros) in namibia.rabies in kudu is unique to namibia and two major peaks in the epizootic have occurred since it was first noted in 1977. due to the large numbers of kudu that were affected, it was suspected that horizontal transmission of rabies occurs among kudu and that rabies was being maintained independently within the namibian kudu population - separate from canid cycles, despite geographic overlap. in this study, it was our aim to show, through phylogenetic analyses, that rabies was being maintained inde ...201323527015
evaluation of an indirect rapid immunohistochemistry test for the differentiation of rabies virus variants.cost effective diagnostic tests are needed in rabies virus (rabv) enzootic areas to study the prevalence, distribution, and transmission of rabies virus among reservoir hosts. to reduce the associated costs of acquiring and maintaining specialized laboratory equipment, an indirect rapid immunohistochemistry test (irit), for the detection and differentiation of rabv variants, was evaluated by traditional light microscopy. the irit utilizes fresh frozen brain touch impressions or cell culture mono ...201323541783
effect of culture ph on recombinant antibody production by a new human cell line, f2n78, grown in suspension at 33.0 °c and 37.0 °c.the human host cell line, f2n78, is a new somatic hybrid cell line designed for therapeutic antibody production. to verify its potential as a human host cell line, recombinant f2n78 cells that produce antibody against rabies virus (rf2n78) were cultivated at different culture ph (6.8, 7.0, 7.2, 7.4, and 7.6) and temperatures (33.0 °c and 37.0 °c). regardless of the culture temperature, the highest specific growth rate was obtained at a ph of 7.0-7.4. lowering the culture temperature from 37.0 °c ...201323553031
characterization and potential diagnostic application of monoclonal antibodies specific to rabies virus.rabies is invariably a fatal encephalomyelitis that is considered to be a serious public health problem. it is necessary to develop standard rabies virus diagnostic tools, especially for diagnosing the strains prevalent in china.201023554655
evaluation of a non-invasive, inhalational challenge method for rabies vaccine potency assay.veterinary rabies vaccines are essential for safeguarding the public from exposure to rabies virus, as vaccination of domestic animals provides a barrier between humans and wildlife reservoirs. ensuring rabies vaccines are potent and effective is paramount in preventing human exposure to rabies virus. the national institutes of health (nih) test, a mouse vaccination-challenge assay, is the most widely used and internationally recognized assay for potency testing of inactivated rabies vaccines, a ...201323557669
characterization of a wild rabies virus isolate of porcine origin in china.rabies virus (rabv) that circulates worldwide in a variety of mammals can cause fatal encephalomyelitis. gd-sh-01, a street rabies virus, was isolated from a rabid pig in china. we investigated the pathogenicity of gd-sh-01 in suckling and adult mice, and compared the susceptibility of na and bhk-21 cells in the culture to infection by gd-sh-01 and cvs-24. the complete gd-sh-01 genome sequence was determined and compared with known rabv wild strains to understand the mutations and genetic divers ...201323567821
prevalence of neutralizing antibodies to rabies virus in serum of seven species of insectivorous bats from colorado and new mexico, united states.we determined the presence of rabies-virus-neutralizing antibodies (rvna) in serum of 721 insectivorous bats of seven species captured, sampled, and released in colorado and new mexico, united states in 2003-2005. a subsample of 160 bats was tested for rabies-virus rna in saliva. we sampled little brown bats (myotis lucifugus) at two maternity roosts in larimer county, colorado; big brown bats (eptesicus fuscus) at three maternity roosts in morgan county, colorado; and big brown bats at five mat ...201323568912
human contacts with oral rabies vaccine baits distributed for wildlife rabies management--ohio, 2012.baits laden with oral rabies vaccines are important for the management of wildlife rabies in the united states. in august 2012, the wildlife services program of the u.s. department of agriculture's animal and plant health inspection service began a field trial involving limited distribution of a new oral rabies vaccine bait in five states, including ohio. the vaccine consisted of live recombinant human adenovirus type 5 vector, expressing rabies virus glycoprotein (adrg1.3) (onrab). a previously ...201323575240
complete genome sequence of rabies virus cvs-24 from china.the entire genome of the mouse-adapted rabies virus strain cvs-24 (challenge virus standard 24), was sequenced. the overall length of the genome was 11,927 nucleotide (nt), comprising a leader sequence of 58 nt, a nucleoprotein (n) gene of 1353 nt, phosphoprotein (p) gene of 894 nt, a matrix protein (m) gene of 609 nt, a glycoprotein (g) gene of 1575 nt, an rna-dependent rna polymerase (rdrp, l) gene of 6384 nt and a trailer region of 70 nt. there was a tgaaaaaaa (tg7) consensus sequence at the ...201323575882
comparison of a modified shell vial culture procedure with conventional mouse inoculation for rabies virus isolation.rabies is a neurotropic disease that is often lethal. the early diagnosis of rabies infection is important and requires methods that allow for the isolation of the virus from animals and humans. the present study compared a modified shell vial (msv) procedure using 24-well tissue culture plates with the mouse inoculation test (mit), which is considered the gold standard for rabies virus isolation. thirty brain samples (25 positive and 5 negative by the fluorescent antibody test) obtained from di ...201323579811
silencing tnf-α in macrophages and dendritic cells for arthritis treatment.tumour necrosis factor (tnf)-α secreted by macrophages and dendritic cells (dcs) plays a predominant role in arthritis. our previous studies suggest that a small peptide, rvg-9r (29-aa peptide derived from the rabies virus glycoprotein, fused to 9r residues), can deliver small interfering rna (sirna) to macrophages and dcs. we therefore tested whether knockdown of tnf-α expression in macrophages and dcs by rvg-9r/bound sirna targeting tnf-α reduces the severity of collagen antibody-induced arthr ...201323582054
anthropogenic roost switching and rabies virus dynamics in house-roosting big brown bats.big brown bats (eptesicus fuscus) are the most commonly encountered rabid bat in north america and represent an important source of wildlife rabies epizootics. urban and suburban colonies of e. fuscus are often evicted from their roosts in houses, with poorly understood consequences for bat dispersal, population dynamics, and rabies virus transmission. we combined radiotelemetry and mark-recapture of e. fuscus with enhanced surveillance to understand the frequency of rabies virus exposure in hou ...201323590325
the present and future of rabies vaccine in animals.an effective strategy for preventing rabies consists of controlling rabies in the host reservoir with vaccination. rabies vaccine has proven to be the most effective weapon for coping with this fatal viral zoonotic disease of warm-blooded animals, including human. natural rabies infection of an individual is always associated with exposure to rabid animals, and the duration of clinical signs can vary from days to months. the incubation period for the disease depends on the site of the bite, seve ...201323596586
assessing the rabies control and surveillance systems in brazil: an experience of measures toward bats after the halt of massive vaccination of dogs and cats in campinas, sao paulo.bats are less vulnerable to forest fragmentation than any other mammal, and for that reason, some species can disperse to peri-urban or urban areas. insectivorous bats are abundant in urban areas due to the density of artificial roosts and insects attracted by city lights. inter-species transmission of the rabies virus between bats can occur, and this is the most probable mechanism of virus circulation in bat populations. bats can also transmit the rabies virus to other mammal species, like dogs ...201323597620
evaluation of knowledge, attitudes, and practices of deer owners following identification of a cluster of captive deer with rabies in pennsylvania in july 2010.to evaluate knowledge, attitudes, and practices of deer owners following identification of a cluster of captive deer with rabies as an aid for the development of rabies prevention educational materials.201323600787
virus infections in the nervous system.virus infections usually begin in peripheral tissues and can invade the mammalian nervous system (ns), spreading into the peripheral (pns) and more rarely the central (cns) nervous systems. the cns is protected from most virus infections by effective immune responses and multilayer barriers. however, some viruses enter the ns with high efficiency via the bloodstream or by directly infecting nerves that innervate peripheral tissues, resulting in debilitating direct and immune-mediated pathology. ...023601101
human rabies: neuropathogenesis, diagnosis, and management.rabies is an almost invariably fatal disease that can present as classic furious rabies or paralytic rabies. recovery has been reported in only a few patients, most of whom were infected with bat rabies virus variants, and has been associated with promptness of host immune response and spontaneous (immune) virus clearance. viral mechanisms that have evolved to minimise damage to the cns but enable the virus to spread might explain why survivors have overall good functional recovery. the shorter ...201323602163
humoral immune response to oral rabies vaccination in raccoon kits: problems and implications.little is known about the immunogenicity of raboral v-rg(®) (v-rg), an oral rabies vaccine, in raccoon kits (procyon lotor). the objectives of this study were to characterize the immunogenicity of v-rg in young kits and investigate the potential impact of maternal antibodies on response to vaccination of nursing raccoon kits. raccoon kits (n=30) were vaccinated at either 3 weeks of age, 7 weeks of age, or assigned as contact controls. nineteen kits (73%) that were whelped by unvaccinated mothers ...201323602534
control and prevention of canine rabies: the need for building laboratory-based surveillance capacity.dogs are the source of more than 99% of human rabies virus infections in endemic regions. without postexposure prophylaxis, almost all cases are fatal, making rabies the most lethal infectious disease. tens of thousands of deaths are reported annually, but the official figures are believed to be gross underestimates. controlling canine rabies, especially in free-ranging dogs, is the first priority to reduce the burden of human disease. because of their limited medical infrastructure, most endemi ...201323603498
importance of rabies virus nucleoprotein in viral evasion of interferon response in the brain.by using a cultured neuroblastoma cell line, the present authors recently showed that the n protein of virulent rabies virus fixed strain nishigahara (ni), but not that of the attenuated derivative ni-ce, mediates evasion of induction of type i interferon (ifn). in this study, to determine whether ni n protein indeed fulfills this function in vivo, the abilities to suppress ifn responses in the mouse brain of ni-ce and the virulent chimeric virus ce(nin), which has the n gene from ni in the gene ...201323607781
unilateral cerebellar hypoplasia and mesencephalic malformation in a hanoverian foal.neurological cases, especially in foals, are rare in the daily practical work. the most common causes are traumata and infectious diseases of the central nervous system (cns). this case report provides further insights into the wide spectrum of possible neuropathological lesions by detailing a complex malformation with unilateral neurological signs that occurred later post natum. thus, clinicians should also be aware of malformations in case of respective neurological patients. a hanoverian foal ...201323608891
secretion of truncated recombinant rabies virus glycoprotein with preserved antigenic properties using a co-expression system in hansenula polymorpha.rabies virus infection remains a serious public health threat in the developing world, where cost-concerns make wide-scale public health interventions impractical. the development of novel and inexpensive elisa diagnostic antigens is critical in early detection and prevention of complications. the transmembrane glycoprotein (g) of rabies virus (rv) contains an external domain capable of inducing the synthesis of anti-rabies, virus-neutralizing antibodies, in infected or immunized hosts. in our s ...201323625226
favourable outcome in a patient bitten by a rabid bat infected with the european bat lyssavirus-1.the classic rabies virus (genotype 1) has been eliminated in western europe, but related lyssaviruses still circulate in local bats. in august 2010, a belgian photographer was bitten upon provocation of a disoriented eptesicus serotinus bat in spain. the bat was infected with european bat lyssavirus-1 (genotype 5). the isolate proved highly neurovirulent in mice. the patient had received preventive rabies immunisations years before the incident and received two boosters with the hdcv rabies vacc ...201623627196
discrepancies in data reporting for rabies, africa.human rabies is an ancient disease but in modern times has primarily been associated with dog rabies-endemic countries of asia and africa. from an african perspective, the inevitable and tragic consequences of rabies require serious reflection of the factors that continue to drive its neglect. established as a major disease only after multiple introductions during the colonial era, rabies continues to spread into new reservoirs and territories in africa. however, analysis of reported data identi ...201323628197
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