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[rhabdoviruses].the family rhabdoviridae has a non-segmented single stranded negative-sense rna and its genome ranges in size from approximately 11 kb to almost 16 kb. it is one of the most ecologically diverse families of rna viruses with members infecting a wide range of organisms. the five structural protein genes are arranged in the same linear order (3'-n-p-m-g-l-5') and may be interspersed with one more additional accessory gene. for many years, a full of knowledge of the rhabdoviridae has been establishe ...201224153229
serum microrna expression profiling in mice infected with rabies virus.serum or plasma micrornas (mirnas) are potential biomarkers for the diagnosis for cancer and prenatal diseases. this study was conducted to investigate whether rabies virus causes a change in serum mirna expression.201124159471
epidemiologic features of animal bite cases occurring in rabies-endemic areas of korea, 2005 to 2009.human rabies is a reemerging infectious disease in korea. there was no human rabies case for 14 years until the disease had reoccurred in 1999. to prevent occurrence of human rabies, surveillance for animal bite patients in rabies endemic areas in korea was conducted since 2005 as a part of a human rabies control program. the animal bite cases were analyzed to determine whether patients were treated according to the post-exposure prophylaxis (pep) guideline of the korea centers for disease contr ...201224159481
efficient n-glycosylation at position 37, but not at position 146, in the street rabies virus glycoprotein reduces pathogenicity.most street rabies viruses have two n-glycosylation sites in their glycoproteins (g proteins), i.e., at asn(37) and asn(319), but asn(37) is usually not core-glycosylated in an efficient manner. previously, we reported the possible roles of single additional n-glycosylations at asn(194) or asn(247) in the cell adaptation and reduced pathogenicity of a street rabies virus, which suggest that n-glycosylation is closely related to the evolution of rabies viruses. in this study, we characterized two ...201424177272
the coelomic fluid of the sea urchin tripneustes depressus shows antiviral activity against suid herpesvirus type 1 (shv-1) and rabies virus (rv).several studies have reported that molecules extracted from invertebrates have activity against different viruses, even against those that do not infect these organisms in their environment. one of the main mechanisms against pathogens in these organisms is the production of antimicrobial peptides. the objective of this study was to determine whether the coelomic fluid (cf) of the sea urchin tripneustes depressus has activity against suid herpesvirus type 1 (shv-1) and/or rabies virus (rv). we t ...201424188747
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
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
naturally occurring rabies virus and neutralizing antibody in two species of insectivorous bats of new york state.seven colonies of eptesicus fuscus , the big brown bat, and five colonies of myotis lucifugus , the little brown bat, in new york state were sampled for rabies virus and virus-neutralizing antibody. eight of 278 e. fuscus were found to have virus, while 18 of 187 had antibody titers of ≥1:8. one of 333 m. lucifugus yielded virus, while three of 127 had antibody. these data demonstrate the presence of rabies virus as well as immunity to rabies in some insectivorous bats of new york state. evaluat ...197724228955
preparation and diagnostic use of a novel recombinant single-chain antibody against rabies virus glycoprotein.rabies virus (rabv) causes a fatal infectious disease, but effective protection may be achieved with the use of rabies immunoglobulin and a rabies vaccine. virus-neutralizing antibodies (vna), which play an important role in the prevention of rabies, are commonly evaluated by the rabv neutralizing test. for determining serum vna levels or virus titers during the rabv vaccine manufacturing process, reliability of the assay method is highly important and mainly dependent on the diagnostic antibody ...201424241896
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
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
development of a reverse genetics system for the ag strain of rabies virus in china.the ag rabies virus strain has been attenuated through multiple passages in cells and is now used as a vaccine strain in china. we attempted to develop a reverse genetics system using the ag strain. recombinant full-length genomic cdna was flanked by a hammerhead ribozyme and the hepatitis delta virus ribozyme. three helper plasmids encoding the nucleoprotein, the phosphoprotein, and the large protein were produced and introduced together with a plasmid containing the full-length ag viral genome ...201424272786
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
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
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
aptamer-based therapeutics: new approaches to combat human viral diseases.viruses replicate inside the cells of an organism and continuously evolve to contend with an ever-changing environment. many life-threatening diseases, such as aids, sars, hepatitis and some cancers, are caused by viruses. because viruses have small genome sizes and high mutability, there is currently a lack of and an urgent need for effective treatment for many viral pathogens. one approach that has recently received much attention is aptamer-based therapeutics. aptamer technology has high targ ...201324287493
comparative proteomics analysis of mice lymphocytes in early stages of infection by different strains of rabies virus.the cns immune response to rabies virus has been shown to be influenced by virulence of the virus strains. there is no comprehensive report of the peripheral immune response against different strains of rabies virus. in this report we used a comparative proteome analysis to find the early events in the spleen lymphocytes of mice infected by a street strain and an attenuated strain of the rabies virus. differentially expressed proteins were identified which play important biological roles such as ...201224293818
development of monoclonal antibodies suitable for rabies virus antibody and antigen detection.the control of an infectious viral disease as rabies is made easier by rapid and accurate diagnosis. successful rabies prophylaxis is dependent upon the active immunization with vaccine along with passive administration of rabies virus neutralizing antibodies which together clear the virus before widespread infection of central nervous system occurs. the present study aimed at the development of monoclonal antibodies (mabs) suitable for rabies virus antibody and antigen detection. for the produc ...201224293819
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
[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
enhancement of antibody production against rabies virus by uridine 5'-triphosphate in mice.extracellular nucleotides such as adenosine 5'-triphospate (atp) and uridine 5'-triphosphate (utp) interact with p2 purinergic receptors on the surface of phagocytic cells and induce various physiological reactions. in this study, the production of antibody in mice immunized with an inactivated rabies vaccine containing these nucleotides was investigated. injection of inactivated rabies vaccine with utp, but not with atp, induced significantly higher serum antibody production in mice. the enhanc ...201424309427
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
innate antiviral signalling in the central nervous system.the innate immune system mediates protection against neurotropic viruses capable of infecting the central nervous system (cns). neurotropic viruses include herpes simplex virus (hsv), west nile virus (wnv), rabies virus, la crosse virus, and poliovirus. viral infection triggers activation of pattern recognition receptors (prrs) such as toll-like receptors (tlrs), retinoic acid-inducible gene 1 (rig-i) like receptors (rlrs), nucleotide-binding oligomerization domain (nod)-like receptors (nlrs), a ...201424316012
[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
a sensitive in vitro assay for the detection of residual viable rabies virus in inactivated rabies vaccines.rabies is a viral disease transmitted through bites from rabid animals and can be prevented by vaccines. clinically used rabies vaccines are prepared from inactivated rabies viruses grown in cell cultures or embryonated eggs. in japan and across the world, tests that confirm complete inactivation, such as the in vivo suckling mouse assay, in which suckling mice are intracerebrally inoculated with vaccine products, are required for quality control. in this study, we developed a novel cell-based i ...201424321529
lentiviral vectors enveloped with rabies virus glycoprotein can be used as a novel retrograde tracer to assess nerve recovery in rat sciatic nerve injury models.retrograde labeling has become the new "gold standard" technique to evaluate the recovery of injured peripheral nerves. in this study, lentiviral vectors with rabies virus glycoprotein envelop (rabv-g-lv) and rfp genes are injected into gastrocnemius muscle to determine the location of rfp in sciatic nerves. we then examine rfp expression in the l4-s1 spinal cord and sensory dorsal root ganglia and in the rat sciatic nerve, isolated schwann cells, viral dose to expression relationship and the us ...201424326614
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
molecular characterization of a rabies virus isolate from a rabid dog in hanzhong district, shaanxi province, china.a canine rabies virus, shaanxi-hz-6, was isolated in shaanxi province, china, in 2009. its genome has been completely sequenced and found to be closely related to the china i rabies virus strains widely circulating in china. the genomic length was 11,923 base pairs, and the overall organization of the genome was similar to that of other rabies virus isolates. compared with isolates cq92 and j, 84 amino acid substitutions (7 in the n gene, 15 in p, 6 in m, 25 in g, 31 in l) were observed in strai ...201424352434
[genetic characterization of the rabies virus field isolates detected in russian federation within the period 2008-2011].sixty-three gene n fragments of rabies virus field isolates detected within the period 2008-2011 in different regions of russian federation were sequenced. the comparison with previously tested isolates and strains has shown that newly isolated isolates can be placed into five previously described phylogenetic groups: arctic group, central russian group, eurasian group, northern european group, and caucasian group. the arctic group isolates detected in komi republic were identical to previously ...201624354065
hierarchically self-organized monolithic nanoporous membrane for excellent virus enrichment.enrichment of viruses is essential for making high dose viral stocks for vaccines and virus-related research. since the widely used ultracentrifugation for concentrating viral stock requires ultra-high speed rotation, it easily destroys the activity of some viruses, for instance, hepatitis c virus (hcv), which has a fragile structure and low virus titer. we introduce a novel method to concentrate hcv virus in stock by using a hierarchically self-organized monolithic nanoporous membrane made by s ...201424354273
interaction of rabies virus p-protein with stat proteins is critical to lethal rabies disease.rabies virus (rabv) causes rabies disease resulting in >55,000 human deaths/year. the multifunctional rabv p-protein has essential roles in genome replication, and forms interactions with cellular stat proteins that are thought to underlie viral antagonism of interferon-dependent immunity. however, the molecular details of p-protein-stat interaction, and its importance to disease are unresolved.201424367042
first isolation of a rabid bat infected with european bat lyssavirus in luxembourg.rabid bats are regularly reported in europe, especially in countries that have implemented a bat surveillance network. in may 2013, bat rabies was evidenced for the first time in luxembourg (southern city of differdange). the rabies virus, an eblv-1b strain, was diagnosed in a serotine bat that bit a 29-year-old male person while he was asleep. the man received rapidly a post-exposure rabv treatment and was put under strict medical supervision.201524373212
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 and protection of red foxes (vulpes vulpes) against rabies using onrab, an adenovirus-rabies recombinant vaccine.twenty-seven red foxes (vulpes vulpes) were each offered a bait containing onrab, a recombinant oral rabies vaccine that uses a human adenovirus vector to express the immunogenic rabies virus glycoprotein; 10 controls received no vaccine baits. serum samples collected from all foxes before treatment, and each week post-treatment for 16 weeks, were tested for the presence of rabies virus neutralizing antibody (rvna). in the bait group, a fox was considered a responder to vaccination if serum samp ...201424374501
survival of rabid rabbits after intrathecal immunization.rabies is a fatal zoonotic disease for which no effective treatment measures are currently available. rabies virus (rabv) has anti-apoptotic and anti-inflammatory properties that suppress nerve cell damage and inflammation in the cns. these features imply that the elimination of rabv from the cns by appropriate treatment could lead to complete recovery from rabies. ten rabbits showing neuromuscular symptoms of rabies after subcutaneous (sc) immunization using commercially available vaccine conta ...201424397792
first report of angiostrongylus vasorum and hepatozoon from a red fox (vulpes vulpes) from west virginia, usa.angiostrongylus vasorum was identified in the lungs of a red fox (vulpes vulpes) from west virginia, united states (us), indicating a new geographical location for this metastrongylid nematode. the fox was euthanized and submitted for necropsy after displaying erratic behavior. we did not detect rabies virus or canine distemper virus from the fox. we observed bronchopneumonia associated with a. vasorum infection disseminated in both lungs. in addition, protozoal meronts were observed in the live ...201424412356
the live vector approach-viruses.recombinant dna technology has made it possible to express foreign genes in viruses and bacteria. this has led to the idea of engineering live attenuated vaccines to express protective antigens from foreign pathogens. vaccinia virus, the smallpox vaccine, has been used to ploneer this approach. several hundred recombinants have been recorded in the literature and many of them have been shown to protect animals against challenge with the appropriate pathogen. although mixed results have been obta ...199124424925
diagnostic evaluation of rt-pcr-elisa for the detection of rabies virus.rabies is primarily a disease of terrestrial and airborne mammals. in most cases, rabies is diagnosed primarily on the basis of clinical symptoms and signs, and a corroborative history of or evidence of an animal bite, death of an animal and incomplete or no vaccination following exposure. the facility for laboratory diagnosis and confirmation of rabies is available in only a few institutions in india. diagnostic tests using conventional assays like fluorescent antibody test (fat) are unreliable ...201424426319
rabies virus glycoprotein variants display different patterns in rabies monosynaptic tracing.rabies virus (rv) has been widely used to trace multi-synaptic neuronal circuits. the recent development of glycoprotein-deficient rabies virus (rv-δg) expressing various proteins has enabled analyzes of both the structure and function of neuronal circuits. the main advantage of rv-δg is its ability to trace monosynaptic circuits by the complementation of rabies virus glycoprotein (rvg), but it has the disadvantage of cytotoxicity. several strain variants of rv have different biological characte ...201424427117
rabies in henan province, china, 2010-2012. 201424447764
inhibition of spring viraemia of carp virus replication in an epithelioma papulosum cyprini cell line by rnai.spring viraemia of carp virus (svcv) is an aetiological agent of a serious disease affecting carp farms in europe and is a member of the rhabdoviridae family of viruses. the genome of svcv codes for five proteins: nucleoprotein (n), phosphoprotein (p), matrix protein (m), glycoprotein (g) and rna-dependent rna polymerase (l). rna-mediated interference (rnai) by small interfering rnas (sirnas) is a powerful tool to inhibit gene transcription and is used to study genes important for viral replicat ...201524460815
variability in seroprevalence of rabies virus neutralizing antibodies and associated factors in a colorado population of big brown bats (eptesicus fuscus).in 2001-2005 we sampled permanently marked big brown bats (eptesicus fuscus) at summer roosts in buildings at fort collins, colorado, for rabies virus neutralizing antibodies (rvna). seroprevalence was higher in adult females (17.9%, n = 2,332) than males (9.4%, n = 128; p = 0.007) or volant juveniles (10.2%, n = 738; p<0.0001). seroprevalence was lowest in a drought year with local insecticide use and highest in the year with normal conditions, suggesting that environmental stress may suppress ...201424465996
medium-term cryopreservation of rabies virus samples.the cryopreservation of rabies virus has been described in detail in the literature. to date, little information is available on the use of cryoprotective agents for cold preservation of this virus, and the available data focus only on short-term virus preservation. in this study, we investigated the medium-term cryopreservation of samples of rabies virus using different cryopreservation protocols.201424474007
experimental infection of the bat tick carios fonsecai (acari: ixodidae) with the rabies virus.this study assessed the viability of the rabies virus in the argasid tick carios fonsecai following experimental infection.201424474026
mapping sensory circuits by anterograde transsynaptic transfer of recombinant rabies virus.primary sensory neurons convey information from the external world to relay circuits within the cns, but the identity and organization of the neurons that process incoming sensory information remains sketchy. within the cns, viral tracing techniques that rely on retrograde transsynaptic transfer provide a powerful tool for delineating circuit organization. viral tracing of the circuits engaged by primary sensory neurons has, however, been hampered by the absence of a genetically tractable antero ...201424486087
selection of an aptamer against rabies virus: a new class of molecules with antiviral activity.rabies is a fatal central nervous system (cns) disease caused by the neurotropic rabies virus (rabv). the therapeutic management of rabv infections is still problematic, and novel antiviral strategies are urgently required. we established the rvg-bhk-21 cell line, which expresses rabv glycoprotein on the cell surface, to select aptamers. through 28 iterative rounds of selection, single-stranded dna (ssdna) aptamers were generated by exponential enrichment (selex). a virus titer assay and a real- ...201424486485
icam-1-based rabies virus vaccine shows increased infection and activation of primary murine b cells in vitro and enhanced antibody titers in-vivo.we have previously shown that live-attenuated rabies virus (rabv)-based vaccines infect and directly activate murine and human primary b cells in-vitro, which we propose can be exploited to help develop a single-dose rabv-based vaccine. here we report on a novel approach to utilize the binding of intracellular adhesion molecule-1 (icam-1) to its binding partner, lymphocyte function-associated antigen-1 (lfa-1), on b cells to enhance b cell activation and rabv-specific antibody responses. we used ...201424489846
a recombinant rabies virus encoding two copies of the glycoprotein gene confers protection in dogs against a virulent challenge.the rabies virus (rabv) glycoprotein (g) is the principal antigen responsible for the induction of virus neutralizing antibodies (vna) and is the major modality of protective immunity in animals. a recombinant rabv hep-flury strain was generated by reverse genetics to encode two copies of the g-gene (referred to as hep-dg). the biological properties of hep-dg were compared to those of the parental virus (hep-flury strain). the hep-dg recombinant virus grew 100 times more efficiently in bhk-21 ce ...201424498294
enhancement of immunogenicity and efficacy of a plasmid dna rabies vaccine by nanoformulation with a fourth-generation amine-terminated poly(ether imine) dendrimer.delayed onset of, and low magnitude of, protective immune responses are major drawbacks limiting the practical utility of plasmid vaccination against rabies. in this study we evaluated whether nanoformulation with the novel poly(ether imine) (petim) dendrimer can enhance the immunogenicity and efficacy of a plasmid-based rabies vaccine.201424501540
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
protection of non-human primates against rabies with an adenovirus recombinant vaccine.rabies remains a major neglected global zoonosis. new vaccine strategies are needed for human rabies prophylaxis. a single intramuscular immunization with a moderate dose of an experimental chimpanzee adenovirus (ad) vector serotype sad-v24, also termed adc68, expressing the rabies virus glycoprotein, resulted in sustained titers of rabies virus neutralizing antibodies and protection against a lethal rabies virus challenge infection in a non-human primate model. taken together, these data demons ...201424503087
experimental oral immunization of ferret badgers (melogale moschata) with a recombinant canine adenovirus vaccine cav-2-e3δ-rgp and an attenuated rabies virus srv9.ferret badgers (melogale moschata) are a major reservoir of rabies virus in southeastern china. oral immunization has been shown to be a practical method for wildlife rabies management in europe and north america. two groups of 20 ferret badgers were given a single oral dose of a recombinant canine adenovirus-rabies vaccine, cav-2-e3δ-rgp, or an experimental attenuated rabies virus vaccine, srv9. at 21 days, all ferret badgers had seroconverted, with serum virus-neutralizing antibodies ranging f ...201424506428
safety and serological response to a matrix gene-deleted rabies virus-based vaccine vector in dogs.dogs account for the majority of human exposures and deaths due to rabies virus (rabv) worldwide. in this report, we show that a replication-deficient rabv-based vaccine in which the matrix gene is deleted (rabv-δm) is safe and induces rapid and potent vna titers after a single inoculation in dogs. average vna titers peaked at 3.02 or 5.11 international units (iu/ml) by 14 days post-immunization with a single dose of 10(6) or 10(7) focus forming units (ffu), respectively, of rabv-δm. by day 70 p ...201424508037
engineering, expression in transgenic plants and characterisation of e559, a rabies virus-neutralising monoclonal antibody.rabies post-exposure prophylaxis (pep) currently comprises administration of rabies vaccine together with rabies immunoglobulin (rig) of either equine or human origin. in the developing world, rig preparations are expensive, often in short supply, and of variable efficacy. therefore, we are seeking to develop a monoclonal antibody cocktail to replace rig. here, we describe the cloning, engineering and production in plants of a candidate monoclonal antibody (e559) for inclusion in such a cocktail ...201424511101
phylogeographic analysis of rabies viruses in the philippines.rabies still remains a public health threat in the philippines. a significant number of human rabies cases, about 200-300 cases annually, have been reported, and the country needs an effective strategy for rabies control. to develop an effective control strategy, it is important to understand the transmission patterns of the rabies viruses. we conducted phylogenetic analyses by considering the temporal and spatial evolution of rabies viruses to reveal the transmission dynamics in the philippines ...201424512808
in vitro and in vivo inhibition of rabies virus replication by rna interference.rabies is a zoonotic disease that affects all mammals and leads to more than 55,000 human deaths every year, caused by rabies virus (rabv) (mononegavirales: rhabdoviridae: lyssavirus). currently, human rabies treatment is based on the milwaukee protocol which consists on the induction of coma and massive antiviral therapy. the aim of this study was to assess the decrease in the titer of rabies virus both in vitro and in vivo using short-interfering rnas. to this end, three sirnas were used with ...201324516427
enhancement of blood-brain barrier permeability and reduction of tight junction protein expression are modulated by chemokines/cytokines induced by rabies virus infection.infection with laboratory-attenuated rabies virus (rabv) enhances blood-brain barrier (bbb) permeability, which has been demonstrated to be an important factor for host survival, since it allows immune effectors to enter the central nervous system (cns) and clear rabv. to probe the mechanism by which rabv infection enhances bbb permeability, the expression of tight junction (tj) proteins in the cns was investigated following intracranial inoculation with laboratory-attenuated or wild-type (wt) r ...201424522913
an inactivated recombinant rabies cvs-11 virus expressing two copies of the glycoprotein elicits a higher level of neutralizing antibodies and provides better protection in mice.the rabies virus (rabv) g protein is the primary contributor to the pathogenicity and protective immunity of rabv. in this study, we generated a recombinant rcvs-11-g strain containing two copies of the g protein derived from the pathogenic wild-type (wt) cvs-11 strain and based on its infectious clone. compared with the wtcvs-11 strain, the rcvs-11-g strain possessed a larger virion and 1.4-fold more g protein, but it exhibited a similar growth property to the rcvs-11 strain, including passagin ...201424535572
rvg-peptide-linked trimethylated chitosan for delivery of sirna to the brain.in this work, a peptide derived from the rabies virus glycoprotein (rvg) was linked to sirna/trimethylated chitosan (tmc) complexes through bifunctional peg for efficient brain-targeted delivery of sirna. the physiochemical properties of the complexes, such as sirna complexing ability, size and ζ potential, morphology, serum stability, and cytotoxicity, were investigated prior to studying the cellular uptake, in vitro gene silencing efficiency, and in vivo biodistribution. the rvg-peptide-linked ...201424547943
recent observations on australian bat lyssavirus tropism and viral entry.australian bat lyssavirus (ablv) is a recently emerged rhabdovirus of the genus lyssavirus considered endemic in australian bat populations that causes a neurological disease in people indistinguishable from clinical rabies. there are two distinct variants of ablv, one that circulates in frugivorous bats (genus pteropus) and the other in insectivorous microbats (genus saccolaimus). three fatal human cases of ablv infection have been reported, the most recent in 2013, and each manifested as acute ...201424556791
an animal component free medium that promotes the growth of various animal cell lines for the production of viral vaccines.ipt-afm is a proprietary animal component free medium that was developed for rabies virus (strain lp 2061) production in vero cells. in the present work, we demonstrated the versatility of this medium and its ability to sustain the growth of other cell lines and different virus strains. here, three models were presented: vero cells/rabies virus (strain lp 2061), mrc-5 cells/measles virus (strain aik-c) and bhk-21 cells/rabies virus (strain pv-bhk21). the cell lines were first adapted to grow in ...201424583007
development and evaluation of a new immunohistochemistry-based test for the detection of rabies virus neutralizing antibodies.rabies claims about 55,000 human lives and many hundreds of thousands of livestock every year, worldwide. despite a heavy disease burden, laboratory facilities to diagnose the infection remain scarce in most countries of the developing world where the disease is endemic. rapid fluorescent focus inhibition test (rffit) and fluorescent antibody virus neutralization test (favn) are the common tests done in the rabies diagnostic laboratories to detect and quantitate rabies virus neutralizing antibod ...201424583787
assessing safety and immunogenicity of post-exposure prophylaxis following interchangeability of rabies vaccines in humans.rabies post exposure prophylaxis with cell culture vaccines by either intramuscular route or intradermal route spans over a period of one month. world health organization recommends completing post exposure prophylaxis against rabies with the same cell culture or embryonated egg rabies vaccine and with same route of administration and any deviation from this shall be an exception. in the present study, the safety and immunogenicity of rabies post-exposure prophylaxis was studied prospectively in ...201424584134
development of a multivalent paediatric human vaccine for rabies virus in combination with measles-mumps-rubella (mmr). 201424589425
development and evaluation of a recombinant-glycoprotein-based latex agglutination test for rabies virus antibody assessment.the measurement of neutralizing antibodies induced by the glycoprotein of rabies virus is indispensable for assessing the level of neutralizing antibodies in animals or humans. a rapid fluorescent focus inhibition test (rffit) has been approved by who and is the most widely used method to measure the virus-neutralizing antibody content in serum, but a rapid test system would be of great value to screen large numbers of serum samples. to develop and evaluate a latex agglutination test (lat) for m ...201424590567
negative effects of a disulfide bond mismatch in anti-rabies g protein single-chain antibody variable fragment fv57.rabies virus (rv) causes a fatal infectious disease requiring efficient post-exposure prophylaxis (pep), which includes a rabies vaccine and rabies immunoglobulin (rig). the single-chain antibody variable fragment (scfv), a small engineered antibody fragment derived from an antibody variable heavy chain and light chain, has the potential to replace the current application of rig. in previous studies, we constructed and evaluated an anti-rabies virus g protein scfv (fv57) based on the monoclonal ...201424598312
rabies virus glycoprotein and immune response pattern using recombinant protein or recombinant rna viral vectors.the present study shows the humoral and cellular aspects of immune response generated by a recombinant rabies virus glycoprotein (rrvgp) as compared to those generated by viral vector carrying the rna coding for this protein (rvgp-rna). the rrvgp was synthesized by stably transfected drosophila melanogaster schneider 2 (s2) cells and the rvgp-rna was carried by a recombinant semiliki forest virus (sfv-rvgp). the data show that protein as well as the rna vaccine was capable of inducing reasonably ...201424598721
pdz domain-mediated protein interactions: therapeutic targets in neurological disorders.protein-protein interactions are critical for cellular functioning, and their deregulation is involved in several diseases. targeting these protein interacting domains could be a promising approach in drug designing. one such domain, the pdz domain is encoded by several proteins of the nervous system in particular at the postsynaptic density site of neurons where they contribute to signal transduction pathways and neurotransmission. since pdz domains have well-defined binding sites, often corres ...201424606518
recovery from rabies: a call to arms. 201424607333
improved transduction efficiency of a lentiviral vector for neuron-specific retrograde gene transfer by optimizing the junction of fusion envelope glycoprotein.the vector for neuron-specific retrograde gene transfer (neuret) is a pseudotype of human immunodeficiency virus type 1 (hiv-1)-based vector with fusion glycoprotein type c (fug-c), which consists of the n-terminal region of the extracellular domain of rabies virus glycoprotein (rvg) and the membrane-proximal region of the extracellular domain and the transmembrane/cytoplasmic domains of vesicular stomatitis virus glycoprotein (vsvg). the neuret vector shows a high efficiency of gene transfer th ...201424613797
a bayesian approach for inferring the dynamics of partially observed endemic infectious diseases from space-time-genetic data.we describe a statistical framework for reconstructing the sequence of transmission events between observed cases of an endemic infectious disease using genetic, temporal and spatial information. previous approaches to reconstructing transmission trees have assumed all infections in the study area originated from a single introduction and that a large fraction of cases were observed. there are as yet no approaches appropriate for endemic situations in which a disease is already well established ...201424619442
molecular epidemiology of rabies virus in poland.the paper describes a phylogenetic study of 58 polish isolates of rabies virus collected between 1992 and 2010. sequences of the nucleoprotein (n) and glycoprotein (g) genes approximately 600 bp long were compared with reference sequences (genbank) of european rabies viruses from neighbouring countries. the study confirmed a very high level of homology (94.4-100 %) of the polish rabies virus strains irrespective of the date of isolation. two variants of rabies virus: nee (northeastern europe var ...201424627096
target cells for antibodies detection in rabies vaccine control.rabies causes one of the most lethal zoonotic diseases, with more than 55,000 deaths reported annually. prevention is based on pre-exposure vaccination of individuals at high risk of contracting rabies, and mass vaccination of dog, which are the main vector for transmission to humans. post-exposure prophylaxis includes vaccination and rabies immunoglobulins treatment. the measurement of neutralizing antibodies in sera of vaccinated individuals is a primary concern to determine the efficacy of im ...201424631076
rabies virus-like particles expressed in hek293 cells.rabies is an infectious viral disease with a mortality rate close to 100%. currently, there is a need to generate cheaper and more immunogenic vaccines for the effective prevention of rabies, mostly in developing countries. virus-like particles have been widely used in viral vaccine production due to their high immunogenicity and safety during the production process. rabies virus glycoprotein is the major antigen to trigger a protective immune response and the only protein capable of generating ...201424631077
[production of the monoclonal antibodies to the rabies virus nucleoprotein].five hybridomas secreting monoclonal antibodies (mabs) for the nucleocapsid protein of the rabies virus were obtained through the fusion of the sp2/0 murine myeloma cells with splenocytes of balb/c mice immunized with fixed rabies virus (cvs strain). all hybridomas secret mabs of the igg class that display different specificity to the nucleocapsids of rabies and rabies-related viruses. mabs 2ell showed the specificity for the prevalent in russia rabies viruses that are similar to commercially av ...201624640170
molecular characterization of three ferret badger (melogale moschata) rabies virus isolates from jiangxi province, china.ferret badger (fb) rabies viruses jx09-17(fb), jx09-18 and jx10-37 were isolated from three different regions in jiangxi province, china, in 2009 and 2010. the complete nucleotide sequence identity between these three isolates was 87-93 %. compared with the other chinese rabies virus isolates and vaccine strains, 101 substitutions (53 in jx10-37, 23 in jx09-17(fb) and 25 in jx09-18) in the five structural proteins were observed, and 47 of these substitutions (27 in jx10-37, 14 in jx09-17(fb) and ...201424643334
[calbindin and parvalbumin distribution in spinal cord of normal and rabies-infected mice].rabies is a fatal infectious disease of the nervous system; however, the knowledge about the pathogenic neural mechanisms in rabies is scarce. in addition, there are few studies of rabies pathology of the spinal cord.201424652212
spatial patterns of neutral and functional genetic variations reveal patterns of local adaptation in raccoon (procyon lotor) populations exposed to raccoon rabies.local adaptation is necessary for population survival and depends on the interplay between responses to selective forces and demographic processes that introduce or retain adaptive and maladaptive attributes. host-parasite systems are dynamic, varying in space and time, where both host and parasites must adapt to their ever-changing environment in order to survive. we investigated patterns of local adaptation in raccoon populations with varying temporal exposure to the raccoon rabies virus (rrv) ...201424655158
phylodynamics of vampire bat-transmitted rabies in argentina.common vampire bat populations distributed from mexico to argentina are important rabies reservoir hosts in latin america. the aim of this work was to analyse the population structure of the rabies virus (rabv) variants associated with vampire bats in the americas and to study their phylodynamic pattern within argentina. the phylogenetic analysis based on all available vampire bat-related n gene sequences showed both a geographical and a temporal structure. the two largest groups of rabv variant ...201424661865
early diagnosis of irkut virus infection using magnetic bead-based serum peptide profiling by maldi-tof ms in a mouse model.early diagnosis is important for the prompt post-exposure prophylaxis of lyssavirus infections. to diagnose irkut virus (irkv) infection during incubation in mice, a novel method using magnetic bead-based serum peptide profiling by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (maldi-tof ms) has been established. for this test, serum peptides were concentrated by adsorption to and elution from the magnetic bead-based weak cation ion exchanger. mass spectrograms obt ...201424670473
evaluation of a new five-injection, two-site,intradermal schedule for purified chick embryo cell rabies vaccine: a randomized, open-label, active-controlled trial in healthy adult volunteers in india.human rabies is an ongoing significant public health problem inmany developing countries, with india reporting the highest incidence of rabies-related deaths (∼20,000 per year). many people living in india cannot afford the standard im postexposure prophylaxis (pep) with cell-culture vaccines, which are administered using a 5-dose regimen developed in essen, germany. a potentially less expensive intradermal (id) regimen, based on the essen regimen, has been developed at the kempegowda institute ...200524672132
a large-scale, rapid public health response to rabies in an organ recipient and the previously undiagnosed organ donor.this article describes and contrasts the public health response to two human rabies cases: one organ recipient diagnosed within days of symptom onset and the transplant donor who was diagnosed 18 months post-symptom onset. in response to an organ-transplant-related rabies case diagnosed in 2013, organ donor and recipient investigations were conducted by multiple public health agencies. persons with potential exposure to infectious patient materials were assessed for rabies virus exposure. an exp ...201424673934
ginsenoside re as an adjuvant to enhance the immune response to the inactivated rabies virus vaccine in mice.the inactivated rabies virus vaccine (rv) is a relatively expensive vaccine, prone to failure in some cases. ginsenoside re (re) is a saponin isolated from panax ginseng, and has an adjuvant property. here the adjuvant effect of re to improve the immune response to the rv is evaluated in mice. icr mice were immunized with saline, 2.50mg/kg re, 20μl rv, 100μl rv, or 20μl of rv adjuvanted with re (1.25, 2.50 or 5.00mg/kg). different time points after boosting, we measured serum antibodies in blood ...201424680943
molecular double-check strategy for the identification and characterization of european lyssaviruses.the "gold standard" for post-mortem rabies diagnosis is the direct fluorescent antibody test (fat). however, in the case of ante-mortem non-neural sample material or decomposed tissues, the fat reaches its limit, and the use of molecular techniques can be advantageous. in this study, we developed and validated a reverse transcription pcr cascade protocol feasible for the classification of samples, even those for which there is no epidemiological background knowledge. this study emphasises on the ...201424681051
diagnosis, management and post-mortem findings of a human case of rabies imported into the united kingdom from india: a case report.human rabies infection continues to be a significant public health burden globally, and is occasionally imported to high income settings where the milwaukee protocol for intensive care management has recently been employed, with limited success in improving survival. access to molecular diagnostics, pre- and post-mortem, and documentation of pathophysiological responses while using the milwaukee protocol, can add useful insights for the future of rabies management.201424708671
generation of recombinant rabies virus cvs-11 expressing egfp applied to the rapid virus neutralization test.the determination of levels of rabies virus-neutralizing antibody (vna) provides the foundation for the quantitative evaluation of immunity effects. the traditional fluorescent antibody virus neutralization test (favn) using a challenge virus standard (cvs)-11 strain as a detection antigen and staining infected cells with a fluorescein isothiocyanate (fitc)-labeled monoclonal antibody, is expensive and high-quality reagents are often difficult to obtain in developing countries. indeed, it is ess ...201424714411
[rabies in potos flavus identified in madre de dios, peru].the potos flavus is a nocturnal mammal that lives in neotropical forests from central america to south america. a study of four cases of rabies in potos flavus was conducted; these occurred in april 2012 in the madre de dios region in peru and were collected as part of epidemiological surveillance. the analysis performed in the regional reference laboratory of madre de dios determined the presence of the rabies virus antigen in three of the brain tissue samples. results were verified in the labo ...201424718532
an anterograde rabies virus vector for high-resolution large-scale reconstruction of 3d neuron morphology.glycoprotein-deleted rabies virus (rabv ∆g) is a powerful tool for the analysis of neural circuits. here, we demonstrate the utility of an anterograde rabv ∆g variant for novel neuroanatomical approaches involving either bulk or sparse neuronal populations. this technology exploits the unique features of rabv ∆g vectors, namely autonomous, rapid high-level expression of transgenes, and limited cytotoxicity. our vector permits the unambiguous long-range and fine-scale tracing of the entire axonal ...201424723034
[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
aptamers targeting rabies virus-infected cells inhibit street rabies virus in vivo.rabies is a viral infection of the cns that is almost always fatal once symptoms occur. no effective treatment of the disease is available and novel antiviral strategies are urgently required. street rabies viruses are field isolates known to be highly neurotropic. aptamers are single-stranded oligonucleotides that bind their targets with high affinity and specificity and thus have potential for use in diagnostic and therapeutic applications. in this study, we demonstrate that the aptamers fo24 ...201424735817
efficient generation of monoclonal antibodies against major structural proteins of rabies virus with suckling mouse brain antigen.the rabies virus is a neurotropic virus that causes fatal disease in humans and animals. however, not all commercial antibodies against rabies virus (rabv) structural proteins are generally available, and production of high-quality monoclonal antibodies (mabs) requires high purification of virus particles and special facilities and is time-consuming. by using rabv-infected suckling mouse brain as antigens in this study, 11 hybridoma cells secreting mabs against rabv were obtained, which showed s ...201424746150
molecular characterization of cryptically circulating rabies virus from ferret badgers, taiwan.after the last reported cases of rabies in a human in 1959 and a nonhuman animal in 1961, taiwan was considered free from rabies. however, during 2012-2013, an outbreak occurred among ferret badgers in taiwan. to examine the origin of this virus strain, we sequenced 3 complete genomes and acquired multiple rabies virus (rabv) nucleoprotein and glycoprotein sequences. phylogeographic analyses demonstrated that the rabv affecting the taiwan ferret badgers (rabv-twfb) is a distinct lineage within t ...201424751120
rabies virus envelope glycoprotein targets lentiviral vectors to the axonal retrograde pathway in motor neurons.rabies pseudotyped lentiviral vectors have great potential in gene therapy, not least because of their ability to transduce neurons following their distal axonal application. however, very little is known about the molecular processes that underlie their retrograde transport and cell transduction. using multiple labeling techniques and confocal microscopy, we demonstrated that pseudotyping with rabies virus envelope glycoprotein (rv-g) enabled the axonal retrograde transport of two distinct subt ...201424753246
limited brain metabolism changes differentiate between the progression and clearance of rabies virus.central nervous system (cns) metabolic profiles were examined from rabies virus (rabv)-infected mice that were either mock-treated or received post-exposure treatment (pet) with a single dose of the live recombinant rabv vaccine trigas. cns tissue harvested from mock-treated mice at middle and late stage infection revealed numerous changes in energy metabolites, neurotransmitters and stress hormones that correlated with replication levels of viral rna. although the large majority of these metabo ...201424763072
multiple lesions by vampire bat bites in a patient in niterói, brazil - case report.over the last few centuries, the expansion of urbanization brought bats closer to urbanized areas, increasing the risk of accidents by bat bites. the morphology of bat bites can be varied, usually having an elliptical shape, about 0.5 cm along its greatest length, and the characteristic corkscrew bite pattern. the authors present the case of a patient who was repeatedly bitten by vampire bats for two months. a polymerase chain reaction was performed in the cutaneous nerves at the base of the hai ...201524770518
rabies: risk, prognosis and prevention.while the uk was declared free from rabies over 100 years ago, the disease remains a significant cause of death in many other countries around the world. it is hoped that eradication programmes in affected countries will succeed in the long term but, until then, prompt and thorough treatment can prevent people who have potentially been in contact with the rabies virus from developing this infection. this article provides a review of the disease and its prevention.201424772797
health evaluation and survey of zoonotic pathogens in free-ranging capybaras (hydrochoerus hydrochaeris).capybaras (hydrochoerus hydrochaeris) are the world's largest rodents and play an epidemiologic role in the transmission of zoonotic pathogens, including the causative agents of brazilian spotted fever, leptospirosis, and others. we surveyed the health of 31 free-ranging capybaras at the alberto löfgren state park, são paulo, brazil using a variety of diagnostic methods. hematology and serum chemistry were consistent with mild malnutrition and parasitism but did not indicate severe physiologic i ...201424779462
antibodies to rabies virus in terrestrial wild mammals in native rainforest on the north coast of são paulo state, brazil.rabies causes thousands of human and animal deaths worldwide each year. the emergent importance of rabies in wild animals demonstrates the necessity of epidemiologic studies of infection in these species toward the development of better strategies for prevention and control of rabies. we analyzed the circulation of rabies virus among wildlife species from a native rainforest in são paulo state, brazil. we used the rapid fluorescent focus inhibition test (rffit) to test for rabies virus-neutraliz ...201424779464
vampire bat rabies: ecology, epidemiology and control.extensive surveillance in bat populations in response to recent emerging diseases has revealed that this group of mammals acts as a reservoir for a large range of viruses. however, the oldest known association between a zoonotic virus and a bat is that between rabies virus and the vampire bat. vampire bats are only found in latin america and their unique method of obtaining nutrition, blood-feeding or haematophagy, has only evolved in the new world. the adaptations that enable blood-feeding also ...201424784570
rabies-virus-glycoprotein-pseudotyped recombinant baculovirus vaccine confers complete protection against lethal rabies virus challenge in a mouse model.rabies virus has been an ongoing threat to humans and animals. here, we developed a new strategy to generate a rabies virus vaccine based on a pseudotyped baculovirus. the recombinant baculovirus (bv-rvg/rvg) was pseudotyped with the rabies virus glycoprotein (rvg) and also simultaneously expressed another rvg under the control of the immediate early cmv promoter. in vitro, this rvg-pseudotyped baculovirus vector induced syncytium formation in insect cells and displayed more efficient gene deliv ...201424793501
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