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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
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
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
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
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
concomitant administration of gonacon™ and rabies vaccine in female dogs (canis familiaris) in mexico.mexico serves as a global model for advances in rabies prevention and control in dogs. the mexican ministry of health (mmh) annual application of approximately 16 million doses of parenteral rabies vaccine has resulted in significant reductions in canine rabies during the past 20 years. one collateral parameter of rabies programs is dog population management. enhanced public awareness is critical to reinforce responsible pet ownership. surgical spaying and neutering remain important to prevent r ...201323871822
axonal and subcellular labelling using modified rabies viral vectors.an important aspect of any neural circuit is the placement of its output synapses, at levels ranging from macroscopic to subcellular. the many new molecular tools for locating and manipulating synapses are limited by the viral vectors available for delivering them. adeno-associated viruses are the best current means of labelling and manipulating axons and synapses, but they have never expressed more than one transgene highly enough to label fine axonal structure while also labelling or perturbin ...201323945836
human rabies--south carolina, 2011.on december 3, 2011, a south carolina woman visited a local emergency department (ed) with an overnight history of shortness of breath, diaphoresis, chills, and intermittent paresthesia. the patient was transferred to a referral hospital, where she became comatose and developed multiorgan failure. the patient did not report a history of an animal bite. however, family members subsequently revealed that bats had been observed in the patient's home during the previous summer. family members also r ...201323945770
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
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
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
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
raccoon rabies virus variant transmission through solid organ transplantation.the rabies virus causes a fatal encephalitis and can be transmitted through tissue or organ transplantation. in february 2013, a kidney recipient with no reported exposures to potentially rabid animals died from rabies 18 months after transplantation.201323917290
genetic strain modification of a live rabies virus vaccine widely used in europe for wildlife oral vaccination.in europe, the main reservoir and vector of rabies has been the red fox (vulpes vulpes). oral immunization of foxes with live vaccines, using attenuated rabies strains (sad b19, sad bern), apathogenic mutants of an attenuated strain (sag2) and the vaccinia-rabies glycoprotein recombinant virus vaccine (v-rg), has been shown to be the most effective method for the control and elimination of rabies. among all vaccines currently used for wildlife oral vaccination, one vaccine (marketed as sad bern ...201323899697
pathogenicity of rabies viruses isolated in china: two fixed strains and a street strain.to investigate the virulence characteristics of two fixed strains (ctn and ag) and a street strain (hn10) of rabies viruses isolated in china.201323895700
design and generation of recombinant rabies virus vectors.rabies viruses, negative-strand rna viruses, infect neurons through axon terminals and spread trans-synaptically in a retrograde direction between neurons. rabies viruses whose glycoprotein (g) gene is deleted from the genome cannot spread across synapses. complementation of g in trans, however, enables trans-synaptic spreading of g-deleted rabies viruses to directly connected, presynaptic neurons. recombinant rabies viruses can encode genes of interest for labeling cells, controlling gene expre ...201323887178
involvement of the rabies virus phosphoprotein gene in neuroinvasiveness.rabies virus (rabv), which is transmitted via a bite wound caused by a rabid animal, infects peripheral nerves and then spreads to the central nervous system (cns) before causing severe neurological symptoms and death in the infected individual. despite the importance of this ability of the virus to spread from a peripheral site to the cns (neuroinvasiveness) in the pathogenesis of rabies, little is known about the mechanism underlying the neuroinvasiveness of rabv. in this study, to obtain insi ...201324027304
transgenically targeted rabies virus demonstrates a major monosynaptic projection from hippocampal area ca2 to medial entorhinal layer ii neurons.the enormous potential of modern molecular neuroanatomical tools lies in their ability to determine the precise connectivity of the neuronal cell types comprising the innate circuitry of the brain. we used transgenically targeted viral tracing to identify the monosynaptic inputs to the projection neurons of layer ii of medial entorhinal cortex (mec-lii) in mice. these neurons are not only major inputs to the hippocampus, the structure most clearly implicated in learning and memory, they also are ...201324027288
passive carriage of rabies virus by dendritic cells.the rabies virus (rabv) is highly neurotropic and it uses evasive strategies to successfully evade the host immune system. because rabies is often fatal, understanding the basic processes of the virus-host interactions, particularly in the initial events of infection, is critical for the design of new therapeutic approaches to target rabv. here, we examined the possible role of dendritic cells (dcs) in the transmission of rabv to neural cells at peripheral site of exposure. viral replication onl ...201324024103
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
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
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
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
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
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
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
rvg-mediated calpain2 gene silencing in the brain impairs learning and memory.in the central nervous system, two calpain isoforms are highly expressed: calpain1 and calpain2. here, we show for the first time that activation of the calpain isoform, calpain2, is a necessary event in hippocampal synaptic plasticity and in learning and memory. we developed a fluorescence resonance energy transfer-based animal model to monitor in vivo calpain activation in single cells and in real time. additionally, utilizing a novel rabies virus glycoprotein-chimeric peptide, which enabled t ...201322903378
pyrosequencing of the rabies virus glycoprotein gene to demonstrate absence of vaccine-associated rabies cases following oral vaccination.replication competent vaccines have been used successfully for the control of terrestrial rabies, mainly in wildlife; however, these vaccine strains occasionally may induce rabies. in this study, a pyrosequencing protocol for the rapid identification of vaccine-associated rabies viruses was applied to the 2008-2011 italian epidemic. there was no evidence of vaccine-associated rabies cases following oral vaccination of foxes with the sag2 and sadb19 vaccine strains.201322841448
dorsal area 46 is a major target of disynaptic projections from the medial temporal lobe.the medial temporal lobe (mtl) is responsible for various mnemonic functions, such as association/conjunction memory. the lateral prefrontal cortex (lpfc) also plays crucial roles in mnemonic functions and memory-based cognitive behaviors, for example, decision-making. therefore, it is considered that the mtl and lpfc connect with each other and cooperate for the control of cognitive behaviors. however, there exist very weak, if any, direct inputs from the mtl to the lpfc. employing retrograde t ...201322989578
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
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
molecular characterisation of rabies virus strains in the republic of macedonia.rabies, a worldwide zoonosis, remains a public-health concern despite oral wildlife vaccination in europe. after a ten-year break, macedonia reported eight rabies cases in 2011-2012. two countries (serbia and bulgaria) bordering macedonia are reporting cases in domestic and wild animals. this report describes the genetic characterisation of eight isolates from macedonia compared with representative samples from neighbouring countries. all of the isolates tested belong to the eastern european gro ...201323001721
metagenomic and metabolomic characterization of rabies encephalitis: new insights into the treatment of an ancient disease.rabies virus (rv) infection is a fatal nervous system disorder. we describe a patient who died of rabies despite a neuroprotective intervention. neuropathology showed neuronal loss with abundant rv antigen, genome, and negri bodies, accompanied by intense neuroinflammation, including by cd8(+) t lymphocyte infiltrates. deep sequencing and real-time reverse-transcription polymerase chain reaction revealed rna encoding a bat rv strain together with inflammatory gene induction. rv-infected brain de ...201322927447
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 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
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
[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
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
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
evaluation of rabies biologics against irkut virus isolated in china.an irkut virus (irkv) was recently isolated from a bat in china. the protective ability of rabies biologics available in the chinese market and experimental biologics against the rabies virus (rabv) and irkv were assessed in a hamster model via preexposure prophylaxis (prep) and postexposure prophylaxis (pep) experiments. the results demonstrated that a single dose of rabies vaccine did not induce adequate protection against irkv infection. however, routine prep with three doses of vaccine induc ...201323946522
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
optogenetic strategies to investigate neural circuitry engaged by stress.optogenetic techniques have given researchers unprecedented access to the function of discrete neural circuit elements and have been instrumental in the identification of novel brain pathways that become dysregulated in neuropsychiatric diseases. for example, stress is integrally linked to the manifestation and pathophysiology of neuropsychiatric illness, including anxiety, addiction and depression. due to the heterogeneous populations of genetically and neurochemically distinct neurons in areas ...201323684554
bioeconomic modelling of raccoon rabies spread management impacts in quebec, canada.beginning in 2006, point infection control operations and aerial distribution of oral rabies vaccines along the us border were performed in quebec, canada, to control the potential spread of raccoon rabies. a benefit-cost analysis assessed the economic efficiency of this rabies control programme into the future. in this study, a mathematical simulation model was used to determine the potential spread of raccoon rabies from the 2006 index case, and incidence rates of human post-exposure prophylax ...201322709550
a novel nuclear trafficking module regulates the nucleocytoplasmic localization of the rabies virus interferon antagonist, p protein.regulated nucleocytoplasmic transport of proteins is central to cellular function and dysfunction during processes such as viral infection. active protein trafficking into and out of the nucleus is dependent on the presence within cargo proteins of intrinsic specific modular signals for nuclear import (nuclear localization signals, nlss) and export (nuclear export signals, ness). rabies virus (rabv) phospho (p) protein, which is largely responsible for antagonising the host anti-viral response, ...201222700958
evaluation of a one week intradermal regimen for rabies post-exposure prophylaxis: results of a randomized, open label, active-controlled trial in healthy adult volunteers in india.the currently recommended intradermal regimen for post-exposure prophylaxis spreads over a month period which many times lead to low compliance from the patients. there is a need to introduce and evaluate short course regimens to overcome this problem. this study was conducted to evaluate the immunogenicity and safety of a "new one week intradermal regimen" for rabies post-exposure prophylaxis. a total of 80 healthy adult volunteers were enrolled and allocated randomly either to purified chick e ...201222699446
ecological and anthropogenic drivers of rabies exposure in vampire bats: implications for transmission and control.despite extensive culling of common vampire bats in latin america, lethal human rabies outbreaks transmitted by this species are increasingly recognized, and livestock rabies occurs with striking frequency. to identify the individual and population-level factors driving rabies virus (rv) transmission in vampire bats, we conducted a longitudinal capture-recapture study in 20 vampire bat colonies spanning four regions of peru. serology demonstrated the circulation of rv in vampire bats from all re ...201222696521
the full-length genome analysis of a street rabies virus strain isolated in yunnan province of china.the epidemic of rabies has rapidly increased and expanded in yunnan province in recent years. in order to further analyze and understand the etiological reasons for the rapid expansion of rabies in yunnan, a strain of rabies virus cyn1009d in yunnan was isolated, and the complete genomic sequencing was carried out, and the bioimfomative analysis on genes/encoded proteins and phylogeny with reference to sequences in genbank was performed. the complete genome of cyn1009d was 11923 nt in length and ...201222684475
molecular characterization of viral g gene in emerging and re-emerging areas of rabies in china, 2007 to 2011.in recent years (2007 to 2011), although the overall number of rabies cases in china has decreased, there is evidence of emerging or re-emerging cases in regions without previous rabies cases or with low incidence of rabies. to investigate the origin and the factors affecting the spread of rabies in china, specimens were collected from 2007 to 2011 from provinces with emerging and re-emerging cases and tested for the presence of the rabies virus. positive specimens were combined with sequences f ...201222684474
preparation and identification of anti-rabies virus monoclonal antibodies.to provide a foundation for the development of rapid and specific methods for the diagnosis of rabies virus infection, anti-rabies virus monoclonal antibodies were prepared and rabies virus nucleoprotein and human rabies virus vaccine strain (pv strain) were used as immunogens to immunize 6-8 week old female balb/c mice. spleen cells and sp2/0 myeloma cells were fused according to conventional methods: the monoclonal cell strains obtained were selected using the indirect immunofluorescence test; ...201222684471
whole-brain mapping of direct inputs to midbrain dopamine neurons.recent studies indicate that dopamine neurons in the ventral tegmental area (vta) and substantia nigra pars compacta (snc) convey distinct signals. to explore this difference, we comprehensively identified each area's monosynaptic inputs using the rabies virus. we show that dopamine neurons in both areas integrate inputs from a more diverse collection of areas than previously thought, including autonomic, motor, and somatosensory areas. snc and vta dopamine neurons receive contrasting excitatory ...201222681690
generation and characterization of neutralizing human recombinant antibodies against antigenic site ii of rabies virus glycoprotein.the currently recommended treatment for individuals exposed to rabies virus (rv) is post-exposure prophylaxis (pep) through the combined administration of rabies vaccine and rabies immune globulin (rig). human monoclonal antibodies (mabs) that neutralize rv offer an opportunity to replace rig for rabies pep. here, a combinatorial human fab library was constructed using antibody genes derived from the blood of rv-vaccinated donors. selections of this library against purified rv virions resulted i ...201222678022
molecular epidemiology of rabies in ukraine.to investigate the circulation of rabies virus in ukraine, 78 rabies virus isolates were acquired from 14 states in 2002 and 2008-2010 for characterization. partial sequences of nucleoprotein (359 nt) and glycoprotein (344 nt) genes were compared with those from neighbouring countries. the analysis identified 39 unique nucleoprotein genes and two geographically distinct rv variants belonging to the cosmopolitan lineage. the ukrainian samples were similar to the north-east european lineage (nee) ...201222661376
european pet travel: misleading information from veterinarians and government agencies.inter-country travel of companion animals provides an opportunity for introduction of zoonotic pathogens, such as rabies virus and echinococcus spp. regulations are in place to control this threat, but schengen agreements mean that border controls between some european countries are minimal, and animals may enter countries without any checks that they have been appropriately treated. veterinarians provide an important source of information for people intending to travel with their pets. we condu ...201222639949
detection of rabies viral rna by taqman real-time rt-pcr using non-neural specimens from dogs infected with rabies virus.to determine the burden of rabies in developing countries, a reliable and accurate diagnostic test for the examination of the brains of animals is needed. recently, the number of samples and carcasses submitted to rabies diagnostic units has been declining. methods for obtaining tissues from different regions of the brain are even more difficult, and direct florescent antibody examination may fail if the samples decomposed. the spread of rabies virus to peripheral non-nervous tissues starts earl ...201222626566
role of nuclear factor-κb in oxidative stress associated with rabies virus infection of adult rat dorsal root ganglion neurons.recent studies in an experimental model of rabies showed major structural changes in the brain involving neuronal processes that are associated with severe clinical disease. cultured adult rat dorsal root ganglion (drg) neurons infected with the challenge virus standard-11 strain of rabies virus (cvs) showed axonal swellings and immunostaining for 4-hydroxy-2-nonenal (4-hne), indicating evidence of lipid peroxidation associated with oxidative stress and reduced axonal growth compared to that of ...201222623795
susceptibility and lack of evidence for a viremic state of rabies in the night owl monkey, aotus nancymaae.rabies causes an acute fatal encephalomyelitis in most mammals following infection with rhabdovirus of the genus lyssavirus. little is known about rabies virus infection in species of new world non-human primates (nhp). to investigate the suitability of the owl monkey aotus nancymaae asissue sections examined were unremarkable for inflammation or other histologic signs of rabies a viable animal model for rabies virus candidate vaccine testing, we used clinical presentation, serology, viral isola ...201222612895
community survey after rabies outbreaks, flagstaff, arizona, usa.flagstaff, arizona, usa, experienced notable outbreaks of rabies caused by a bat rabies virus variant in carnivore species in 2001, 2004, 2005, 2008, and 2009. the most recent epizootic involved transmission among skunk and fox populations and human exposures. multiple, wide-ranging control efforts and health communications outreach were instituted in 2009, including a household survey given to community members. although the flagstaff community is knowledgeable about rabies and the ongoing outb ...201222607999
trends in national surveillance data for bat rabies in the united states: 2001-2009.rabies remains an important public health concern in the united states, with most human cases associated with bat rabies virus variants. cases of rabies virus (rv) infection in bats are widely distributed across the continental united states and elsewhere in the americas. in this retrospective study, data on bats submitted to state laboratories for rv diagnosis between 2001 and 2009 were analyzed to investigate epidemiological trends in the united states. season, region, and roosting habits were ...201222607069
segregated pathways carrying frontally derived top-down signals to visual areas mt and v4 in macaques.the bottom-up processing of visual information is strongly influenced by top-down signals, at least part of which is thought to be conveyed from the frontal cortex through the frontal eye field (fef) and the lateral intraparietal area (lip). here we investigated the architecture of multisynaptic pathways from the frontal cortex to the middle temporal area (mt) of the dorsal visual stream and visual area 4 (v4) of the ventral visual stream in macaques. in the first series of experiments, the retr ...201222593054
localization of rabies virus glycoprotein into the endoplasmic reticulum produces immunoprotective antigen.rabies virus surface glycoprotein (rabies g-protein) with (g+rs) and without (g-rs) endoplasmic reticulum retrieval signal was expressed and characterized in tobacco plants. transgenically expressed rabies g-protein was estimated at 0.015-0.38 % of total leaf protein. the relative migration of the rabies g-protein on sds-page was at the position, as anticipated for the viral coat protein (~66 kda). immunolocalization by confocal microscopy established that immunoprotective g+rs expressed in toba ...201222592449
high diversity of rabies viruses associated with insectivorous bats in argentina: presence of several independent enzootics.rabies is a fatal infection of the central nervous system primarily transmitted by rabid animal bites. rabies virus (rabv) circulates through two different epidemiological cycles: terrestrial and aerial, where dogs, foxes or skunks and bats, respectively, act as the most relevant reservoirs and/or vectors. it is widely accepted that insectivorous bats are not important vectors of rabv in argentina despite the great diversity of bat species and the extensive argentinean territory.201222590657
human rabies with initial manifestations that mimic acute brachial neuritis and guillain-barré syndrome.human rabies can be overlooked in places where this disease is now rare. its diagnosis is further confused by a negative history of exposure (cryptogenic rabies), by a guillain-barré syndrome (gbs) type of presentation, or by symptoms indicating another diagnosis, eg, acute brachial neuritis (abn).201222577299
the motor cortex communicates with the kidney.we used retrograde transneuronal transport of rabies virus from the rat kidney to identify the areas of the cerebral cortex that are potential sources of central commands for the neural regulation of this organ. our results indicate that multiple motor and nonmotor areas of the cerebral cortex contain output neurons that indirectly influence kidney function. these cortical areas include the primary motor cortex (m1), the rostromedial motor area (m2), the primary somatosensory cortex, the insula ...201222573695
new introduction and spread of rabies among dog population in bangui.rabies is endemic in the central african republic (car) and a neglected enzootic disease which represents a serious public health problem. before april 2009, rabies was not a notifiable disease in car. vaccination of animals is expensive and not commonly done. in 2005, none rabies case was recorded in bangui. to understand how rabies was introduced and propagated in the city of bangui from 2006 to 2008, we analyzed samplings of dog brain as well as reviewed the records of dog owners. a total of ...201222569561
the spatial and temporal dynamics of rabies in china.recent years have seen a rapid increase in the number of rabies cases in china and an expansion in the geographic distribution of the virus. in spite of the seriousness of the outbreak and increasing number of fatalities, little is known about the phylogeography of the disease in china. in this study, we report an analysis of a set of nucleocapsid sequences consisting of samples collected through the trial chinese national surveillance system as well as publicly available sequences. this sequenc ...201222563518
six fatal cases of classical rabies virus without biting incidents, iran 1990-2010.rabies is an endemic fatal zoonotic disease, commonly transmitted to humans through contact (bites and scratches) with infected animals.201222554714
imported human rabies in a u.s. army soldier - new york, 2011.on august 19, 2011, a male u.s. army soldier with progressive right arm and shoulder pain, nausea, vomiting, ataxia, anxiety, and dysphagia was admitted to an emergency department (ed) in new york for suspected rabies. rabies virus antigens were detected in a nuchal skin biopsy, rabies virus antibodies in serum and cerebrospinal fluid (csf), and rabies viral rna in saliva and csf specimens by state and cdc rabies laboratories. an afghanistan canine rabies virus variant was identified. the patien ...201222552206
validation of the rapid fluorescent focus inhibition test for rabies virus-neutralizing antibodies in clinical samples.monoclonal antibodies are successful biologics in treating a variety of diseases, including the prevention or treatment of viral infections. cl184 is a 1:1 combination of two human monoclonal igg1 antibodies (cr57 and cr4098) against rabies virus, produced in the per.c6 human cell line. the two antibodies are developed as replacements of human rabies immune globulin (hrig) and equine rabies immune globulin (erig) in postexposure prophylaxis (pep). the rapid fluorescent focus inhibition test (rff ...201222547629
passive immunity in the prevention of rabies.prevention of clinical disease in those exposed to viral infection is an important goal of human medicine. using rabies virus infection as an example, we discuss the advances in passive immunoprophylaxis, most notably the shift from the recommended polyclonal human or equine immunoglobulins to monoclonal antibody therapies. the first rabies-specific monoclonal antibodies are undergoing clinical trials, so passive immunisation might finally become an accessible, affordable, and routinely used par ...201222541629
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