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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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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 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
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
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
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
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
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
[assessment and prevention of zoonoses: "one health approach"].zoonotic pathologies represent diseases that can be transmittable from animals to humans and vice versa. in most cases zoonotic agents are bacteria or viruses and represent a huge problem for health. zoonosis could represent easily solvable diseases such as simple infections or even deathly such as prion infections. they could be directly transmittable as tuberculosis or brucellosis or indirectly transmittable through vectors as biological fluids or foods from animal production. the increasing p ...201324303718
resolving the roles of immunity, pathogenesis, and immigration for rabies persistence in vampire bats.bats are important reservoirs for emerging infectious diseases, yet the mechanisms that allow highly virulent pathogens to persist within bat populations remain obscure. in latin america, vampire-bat-transmitted rabies virus represents a key example of how such uncertainty can impede efforts to prevent cross-species transmission. despite decades of agricultural and human health losses, control efforts have had limited success. to establish persistence mechanisms of vampire-bat-transmitted rabies ...201324297874
organization of multisynaptic inputs to the dorsal and ventral dentate gyrus: retrograde trans-synaptic tracing with rabies virus vector in the rat.behavioral, anatomical, and gene expression studies have shown functional dissociations between the dorsal and ventral hippocampus with regard to their involvement in spatial cognition, emotion, and stress. in this study we examined the difference of the multisynaptic inputs to the dorsal and ventral dentate gyrus (dg) in the rat by using retrograde trans-synaptic tracing of recombinant rabies virus vectors. three days after the vectors were injected into the dorsal or ventral dg, monosynaptic n ...201324223172
revised 4-dose vaccine schedule as part of postexposure prophylaxis to prevent human rabies.there is overwhelming evidence that the 4-dose vaccine schedule as part of postexposure prophylaxis to prevent human rabies for previously unvaccinated persons, as recommended by the advisory committee on immunization practices, united states in 2009, is safe and effective. when used appropriately with timely wound care and administration of human rabies immune globulin, the administration of 4 doses of vaccine on days 0, 3, 7, and 14 is likely to induce an adequate,long-lasting antibody respons ...201324084614
proteomics analysis of human brain tissue infected by street rabies virus.in order to extend the knowledge of rabies pathogenesis, a two-dimensional electrophoresis/mass spectrometry based postmortem comparative proteomics analysis was carried out on human brain samples. alteration in expression profile of several proteins was detected. proteins related to cytoskeleton, metabolism, proteasome and immune regulatory systems showed the most changes in expression levels. among these groups, the cytoskeleton related proteins (dynein light chain, β-centractin, tubulin alpha ...201324057270
global gene expression changes in bv2 microglial cell line during rabies virus infection.microglia plays a crucial role during virus pathogenesis in the central nervous system (cns). infection by rabies virus (rabv) causes a fatal infection in the cns of all warm-blooded animals. however, the microglial responses to rabv infection have been scarcely reported. to better understand microglia-rabv interactions at the transcriptional level, a genome wide gene expression profile in mouse microglial cells line bv2 was performed using microarray analysis. the global messenger rna changes i ...201324056016
isolation of a phylogenetically distinct rabies virus from a tufted capuchin monkey (cebus apella) in brazil.a rabies virus isolate (brmk1358 strain) was discovered from a rabid tufted capuchin monkey in brazil. the present study determined the nucleotide sequence of the brmk1358 strain and compared with the rabies viruses isolated from marmosets and other animals in the americas. phylogenetic analyses showed that the brmk1358 strain formed a lineage distant from that of marmoset rabies virus within the chiroptera-related rabies virus cluster. this result suggests that the source of rabies infection in ...201324055656
rabies.rabies has been a scourge of mankind since antiquity. the name itself, ?rabies? is derived from the ancient sanskrit rabhas meaning ?to do violence? and has been found described in medical writings several thousand years old. the rabies virus is an rna virus of the family rhabdoviridae (greek for ?rod-shaped virus?), genus lyssavirus (lyssa being the greek god of frenzy and rage). rabies infections have a worldwide spread, with only a few, mostly island nations laying claim to being ?rabies free ...201324049000
rabies surveillance in the united states during 2012.summary-during 2012, 49 states and puerto rico reported 6,162 rabid animals and 1 human rabies case to the cdc, representing a 2.1% increase from the 6,031 rabid animals and 6 human cases reported in 2011. approximately 92% of reported rabid animals were wildlife. relative contributions by the major animal groups were as follows: 1,953 raccoons (31.7%), 1,680 bats (27.3%), 1,539 skunks (25.0%), 340 foxes (5.5%), 257 cats (4.2%), 115 cattle (1.9%), and 84 dogs (1.4%). compared with 2011, there wa ...201324004227
tracing inputs to inhibitory or excitatory neurons of mouse and cat visual cortex with a targeted rabies virus.cortical inhibition plays a critical role in controlling and modulating cortical excitation, and a more detailed understanding of the neuronal circuits contributing to each will provide more insight into their roles in complex cortical computations. traditional neuronal tracers lack a means for easily distinguishing between circuits of inhibitory and excitatory neurons. to overcome this limitation, we have developed a technique for retrogradely labeling inputs to local clusters of inhibitory or ...201323993841
evolutionary history and phylogeography of rabies viruses associated with outbreaks in trinidad.bat rabies is an emerging disease of public health significance in the americas. the caribbean island of trinidad experiences periodic outbreaks within the livestock population. we performed molecular characterisation of trinidad rabies virus (rabv) and used a bayesian phylogeographic approach to investigate the extent to which outbreaks are a result of in situ evolution versus importation of virus from the nearby south american mainland. trinidadian rabv sequences were confirmed as bat variant ...201323991230
prevalence of rabies in various species in yemen and risk factors contributing to the spread of the disease.this study aimed to describe for the first time the prevalence of the passively-reported rabies virus among different domestic and wild animals submitted to the central veterinary laboratory from various areas in yemen, and to study prevalence proportion ratios (ppr) that contributed to the spread of rabies among animals, and its transmission to humans.201323984026
a previously unknown mechanism in viral pathogenesis leading to effective new vaccines and post-exposure immune treatments of viral infections.investigations with the rabies virus identified a previously unknown mechanism of viral pathogenesis. after ultracentrifugation of a suspension of rabid dog brain and rabies vaccine strains, the supernatant was found to contain active components, as evaluated in an in vitro plaque test. the unexpected detection of active components in non-sedimented material prompted further research and the finding that these components, and not the complete virus, were responsible for paralysis and death. vacc ...201323977809
single domain antibody multimers confer protection against rabies infection.post-exposure prophylactic (pep) neutralizing antibodies against rabies are the most effective way to prevent infection-related fatality. the outer envelope glycoprotein of the rabies virus (rabv) is the most significant surface antigen for generating virus-neutralizing antibodies. the small size and uncompromised functional specificity of single domain antibodies (sdabs) can be exploited in the fields of experimental therapeutic applications for infectious diseases through formatting flexibilit ...201323977032
complete genome sequences of three rabies viruses isolated from rabid raccoon dogs and a cow in korea.the complete genomes of three rabies viruses (bd0406cc, bv9901pj, and 08f40) of two raccoon dogs (nyctereutes procyonoides koreensis) and a cow were determined. the genomic organization is typical of rabies viruses, and the open reading frames of the n, p, m, g, and l genes are 1,353, 894, 609, 1,575, and 6,384 bases in length, respectively. the full genome length of the three strains was 11,928 nucleotides, and the sequence similarity between the rabies viruses at the nucleotide level was 98.5- ...201323975690
enzootic and epizootic rabies associated with vampire bats, peru.during the past decade, incidence of human infection with rabies virus (rabv) spread by the common vampire bat (desmodus rotundus) increased considerably in south america, especially in remote areas of the amazon rainforest, where these bats commonly feed on humans. to better understand the epizootiology of rabies associated with vampire bats, we used complete sequences of the nucleoprotein gene to infer phylogenetic relationships among 157 rabv isolates collected from humans, domestic animals, ...201323969087
intracellular reprogramming of expression, glycosylation, and function of a plant-derived antiviral therapeutic monoclonal antibody.plant genetic engineering, which has led to the production of plant-derived monoclonal antibodies (mab(p)s), provides a safe and economically effective alternative to conventional antibody expression methods. in this study, the expression levels and biological properties of the anti-rabies virus mab(p) so57 with or without an endoplasmic reticulum (er)-retention peptide signal (lys-asp-glu-leu; kdel) in transgenic tobacco plants (nicotiana tabacum) were analyzed. the expression levels of mab(p) ...201323967055
uptake of rabies virus into epithelial cells by clathrin-mediated endocytosis depends upon actin.rabies virus (rabv) causes a fatal zoonotic encephalitis. disease symptoms require replication and spread of the virus within neuronal cells; however, in infected animals as well as in cell culture the virus replicates in a broad range of cell types. here we use a single-cycle rabv and a recombinant vesicular stomatitis virus (rvsv) in which the glycoprotein (g) was replaced with that of rabv (rvsv rabv g) to examine rabv uptake into the african green monkey kidney cell line bs-c-1. combining bi ...201323966407
in vivo differential susceptibility of sensory neurons to rabies virus infection.there is controversy with regard to the entry pathway of the rabies virus (rabv) into the central nervous system (cns). some authors have suggested that the virus inoculated at the periphery is captured and transported to cns only by motor neurons; however, it has been reported that dorsal root ganglia (drg) sensory neurons capture and transport the virus to the spinal cord (sc) and then to the brain. it is probable that preferences for one pathway or another depend on the site of inoculation an ...201323959650
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
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
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
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
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
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
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
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
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
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
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
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
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
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
[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
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
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
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
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
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
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
microarray for identification of the chiropteran host species of rabies virus in canada.species identification through genetic barcoding can augment traditional taxonomic methods, which rely on morphological features of the specimen. such approaches are especially valuable when specimens are in poor condition or comprise very limited material, a situation that often applies to chiropteran (bat) specimens submitted to the canadian food inspection agency for rabies diagnosis. coupled with phenotypic plasticity of many species and inconclusive taxonomic keys, species identification us ...201327605186
[a new approach to postexposure treatment of rabies by complex of immuno- and chemotherapy in belarus].a method for preventive treatment of rabies with a complex of immuno- and chemotherapeutics was developed. rifampicin was used a an etiotropic drug. in the experiments on laboratory animals infected with fixed and street strains of rabies virus it was shown to prolong the incubation period and to increase the survival rate. the protective mechanisms of rifampicin against rabies should be associated with inhibition of rna transcription, as well as immunomodulating function of macrophages, dendrit ...201324734427
[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
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
factors impacting the control of rabies.rabies is a classical zoonosis that has been known to man for ages. the disease can be caused by several viral species in the lyssavirus genus, but the type species, rabies virus (rabv), is by far the most important from a zoonosis perspective. the extreme neurotropism of rabv and the evolutionarily conserved elements and structures of the mammalian brain suggest that this virus evolved an ultimate niche for replication, simultaneously exploiting classical social behavior of a wide diversity of ...201326184959
recent emergence and spread of an arctic-related phylogenetic lineage of rabies virus in nepal.rabies is a zoonotic disease that is endemic in many parts of the developing world, especially in africa and asia. however its epidemiology remains largely unappreciated in much of these regions, such as in nepal, where limited information is available about the spatiotemporal dynamics of the main etiological agent, the rabies virus (rabv). in this study, we describe for the first time the phylogenetic diversity and evolution of rabv circulating in nepal, as well as their geographical relationsh ...201324278494
ultra-deep sequencing of intra-host rabies virus populations during cross-species transmission.one of the hurdles to understanding the role of viral quasispecies in rna virus cross-species transmission (cst) events is the need to analyze a densely sampled outbreak using deep sequencing in order to measure the amount of mutation occurring on a small time scale. in 2009, the california department of public health reported a dramatic increase (350) in the number of gray foxes infected with a rabies virus variant for which striped skunks serve as a reservoir host in humboldt county. to better ...201324278493
mitochondrial dysfunction in rabies virus infection of neurons.infection with the challenge virus standard-11 (cvs) strain of fixed rabies virus induces neuronal process degeneration in adult mice after hindlimb footpad inoculation. cvs-induced axonal swellings of primary rodent dorsal root ganglion neurons are associated with 4-hydroxy-2-nonenal protein adduct staining, indicating a critical role of oxidative stress. mitochondrial dysfunction is the major cause of oxidative stress. we hypothesized that cvs infection induces mitochondrial dysfunction leadin ...201324277436
role of the blood-brain barrier in rabies virus infection and protection.rabies is an acute, progressive encephalitis caused by infection with rabies virus (rabv). it is one of the most important zoonotic infections and causes more than 70,000 human deaths annually ( http://www.rabiescontrol.net ). it has long been held that a rabies infection is lethal in humans once the causative rabv reaches the central nervous system (cns); however, this concept was challenged by the recent recovery of a small number of rabies patients. an analysis of these patients revealed that ...201324264143
rabies virus vector transgene expression level and cytotoxicity improvement induced by deletion of glycoprotein gene.the glycoprotein (g) of rabies virus (rv) is required for binding to neuronal receptors and for viral entry. g-deleted rv vector is a powerful tool for investigating the organization and function of the neural circuits. it gives the investigator the ability to genetically target initial infection to particular neurons and to control trans-synaptic propagation. in this study we have quantitatively evaluated the effect of g gene deletion on the cytotoxicity and transgene expression level of the rv ...201324244660
a next-generation, serum-free, highly purified vero cell rabies vaccine is safe and as immunogenic as the reference vaccine verorab® when administered according to a post-exposure regimen in healthy children and adults in china.as an evolution of its currently licensed rabies vaccine verorab(®), sanofi pasteur has developed a next-generation, serum-free, highly purified vero rabies vaccine (pvrv-ng). through this phase iii clinical trial, we aimed to demonstrate the non-inferiority of pvrv-ng over verorab when administered according to a post-exposure regimen and to assess its clinical safety.201324148575
a multi-dose serological assay suitable to quantify the potency of inactivated rabies vaccines for veterinary use.the mouse vaccination-challenge test, which is the most widely used method for determining the potency of inactivated rabies vaccines, is imprecise, time-consuming, and causes severe distress to the test animals. an alternative single-dose serological method has been implemented in the european pharmacopoeia monograph 0451 to replace the mouse challenge test for batch release. this single-dose limit method provides semi-quantitative results, but is not suitable for quantifying potency. we have n ...201324144483
feature selection methods for identifying genetic determinants of host species in rna viruses.despite environmental, social and ecological dependencies, emergence of zoonotic viruses in human populations is clearly also affected by genetic factors which determine cross-species transmission potential. rna viruses pose an interesting case study given their mutation rates are orders of magnitude higher than any other pathogen--as reflected by the recent emergence of sars and influenza for example. here, we show how feature selection techniques can be used to reliably classify viral sequence ...201324130470
alanine scanning of the rabies virus glycoprotein antigenic site iii using recombinant rabies virus: implication for post-exposure treatment.the safety and availability of the human polyclonal sera that is currently utilized for post-exposure treatment (pet) of rabies virus (rabv) infection remain a concern. recombinant monoclonal antibodies have been postulated as suitable alternatives by who. to this extent, cl184, the rabv human antibody combination comprising monoclonal antibodies (mabs) cr57 and cr4098, has been developed and has delivered promising clinical data to support its use for rabv pet. for this fully human igg1 cocktai ...201324120673
serological investigation of rabies virus neutralizing antibodies in bats captured in the eastern brazilian amazon.in 2004 and 2005 a total of 38 cases of human rabies transmitted by the hematophagous bat desmodus rotundus were registered in the brazilian state of pará; 23 (60.5%) cases occurred in the northeastern region. because of this, a serological investigation for the antibodies of rabies virus was performed in municipalities of the northeastern state of pará, in order to assess whether the virus was circulating among different bat species.201324100701
epidemiology of rabies in bats in texas (2001-2010).to obtain epidemiological information on rabies in bats in texas.201324094260
assessment of risk of possible exposure to rabies among processors and consumers of dog meat in zaria and kafanchan, kaduna state, nigeria.canine rabies is endemic in nigeria. some of the dogs slaughtered for human consumption may be infected with rabies virus, thus exposing handlers of raw dog meat to the disease since the virus may be present in the nerves in the meat. a cross-sectional study was designed and a structured questionnaire was designed and administered to a convenience sample of 160 processors and consumers (100 from zaria and 60 from kafanchan), by face to face interview at the slaughter sites or dog meat sale point ...201324373274
ecology and geography of transmission of two bat-borne rabies lineages in chile.rabies was known to humans as a disease thousands of years ago. in america, insectivorous bats are natural reservoirs of rabies virus. the bat species tadarida brasiliensis and lasiurus cinereus, with their respective, host-specific rabies virus variants agv4 and agv6, are the principal rabies reservoirs in chile. however, little is known about the roles of bat species in the ecology and geographic distribution of the virus. this contribution aims to address a series of questions regarding the e ...201324349592
[evolutionary and transmission characteristics of rabies viruses in asia].to understand the rabies virus (rabv) evolutionary relationship between the strains of china and asia and to know the evolution and transmission characteristics of rabv in asia.201324319952
the phylogeography and spatiotemporal spread of south-central skunk rabies virus.the south-central skunk rabies virus (scsk) is the most broadly distributed terrestrial viral lineage in north america. skunk rabies has not been efficiently targeted by oral vaccination campaigns and represents a natural system of pathogen invasion, yielding insights to rabies emergence. in the present study we reconstructed spatiotemporal spread of scsk in the whole territory of its circulation using a combination of bayesian methods. the analysis based on 241 glycoprotein gene sequences demon ...201324312657
oral vaccination of captive small indian mongoose (herpestes auropunctatus) against rabies.the small indian mongoose (herpestes auropunctatus), a rabies reservoir species on several islands in the caribbean, was successfully immunized against rabies for the first time by offering animals a vaccine bait specifically designed for this small carnivore. the bait contained on average 0.6 ml of the genetically modified replication-competent rabies virus construct spbn gasgas (10(8.5) focus-forming units/ml). three of four mongooses offered a bait developed an immune response above 0.5 iu/ml ...201324502736
quantitative rt-pcr for titration of replication-defective recombinant semliki forest virus.virus titration may constitute a drawback in the development and use of replication-defective viral vectors like semliki forest virus (sfv). the standardization and validation of a reverse transcription quantitative pcr (qrt-pcr) method for sfv titration is presented here. the qrt-pcr target is located within the nsp1 gene of the non-structural polyprotein sfv region (sfv rna), which allows the strategy to be used for several different recombinant sfv constructs. titer determinations were carrie ...201323933080
high prevalence of antibodies against canine adenovirus (cav) type 2 in domestic dog populations in south africa precludes the use of cav-based recombinant rabies vaccines.rabies in dogs can be controlled through mass vaccination. oral vaccination of domestic dogs would be useful in the developing world, where greater vaccination coverage is needed especially in inaccessible areas or places with large numbers of free-roaming dogs. from this perspective, recent research has focused on development of new recombinant vaccines that can be administered orally in a bait to be used as adjunct for parenteral vaccination. one such candidate, a recombinant canine adenovirus ...201323867013
rabies, canine distemper, and canine parvovirus exposure in large carnivore communities from two zambian ecosystems.disease transmission within and among wild and domestic carnivores can have significant impacts on populations, particularly for threatened and endangered species. we used serology to evaluate potential exposure to rabies virus, canine distemper virus (cdv), and canine parvovirus (cpv) for populations of african lions (panthera leo), african wild dogs (lycaon pictus), and spotted hyenas (crocuta crocuta) in zambia's south luangwa national park (slnp) and liuwa plain national park (lpnp) as well ...201323805791
serosurvey for selected viral infections in free-ranging jaguars (panthera onca) and domestic carnivores in brazilian cerrado, pantanal, and amazon.we investigated the exposure of jaguar (panthera onca) populations and domestic carnivores to selected viral infections in the cerrado, amazon, and pantanal biomes of brazil. between february 2000 and january 2010, we collected serum samples from 31 jaguars, 174 dogs (canis lupus familiaris), and 35 domestic cats (felis catus). serologic analyses for antibodies to rabies virus, canine distemper virus (cdv), feline immunodeficiency virus (fiv), and for feline leukemia virus (felv) antigen were co ...201323778599
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
a retrospective study of brain lesions in goats submitted to three veterinary diagnostic laboratories.a retrospective study of brain lesions in goats was conducted to identify the range of lesions and diseases recognized and to make recommendations regarding the best tissues to examine and tests to conduct in order to maximize the likelihood of making a definitive diagnosis in goats that may have had clinical signs referable to the brain. one hundred thirty-nine goats with a brain lesion were identified. the most common lesion, in 52.5% of the goats, was suppurative inflammation. approximately t ...201323794017
the antiviral innate immune response in fish: evolution and conservation of the ifn system.innate immunity constitutes the first line of the host defense after pathogen invasion. viruses trigger the expression of interferons (ifns). these master antiviral cytokines induce in turn a large number of interferon-stimulated genes, which possess diverse effector and regulatory functions. the ifn system is conserved in all tetrapods as well as in fishes, but not in tunicates or in the lancelet, suggesting that it originated in early vertebrates. viral diseases are an important concern of fis ...201324075867
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
presence of virus neutralizing antibodies in cerebral spinal fluid correlates with non-lethal rabies in dogs.rabies is traditionally considered a uniformly fatal disease after onset of clinical manifestations. however, increasing evidence indicates that non-lethal infection as well as recovery from flaccid paralysis and encephalitis occurs in laboratory animals as well as humans.201324069466
travel and non-travel associated rabies post exposure treatment in new south wales residents, australia, 2007-2011: a cross-sectional analysis.australian bat lyssavirus is endemic in australian bats. more australians are travelling to rabies (lyssavirus 1) endemic countries. the nature and frequency of lyssavirus exposures and characteristics of new south wales (nsw) residents exposed have not previously been described.201324211239
host cell tropism mediated by australian bat lyssavirus envelope glycoproteins.australian bat lyssavirus (ablv) is a rhabdovirus of the lyssavirus genus capable of causing fatal rabies-like encephalitis in humans. there are two variants of ablv, one circulating in pteropid fruit bats and another in insectivorous bats. three fatal human cases of ablv infection have been reported with the third case in 2013. importantly, two equine cases also arose in 2013; the first occurrence of ablv in a species other than bats or humans. we examined the host cell entry of ablv, character ...201323849788
analysis of the complete genome of the first irkut virus isolate from china: comparison across the lyssavirus genus.the genome of irkut virus, isolate irkv-thchina12, the first non-rabies lyssavirus from china (of bat origin), has been completely sequenced. in general, coding and non-coding regions of this viral genome are similar to those of other lyssaviruses. however, alignment of the deduced amino acid sequences of the structural proteins of irkv-thchina12 with those of other lyssavirus representatives revealed significant variability between viral species. the nucleoprotein and matrix protein were found ...201323872529
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