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the importance of being short: the role of rabies virus phosphoprotein isoforms assessed by differential ires translation initiation.the rabies virus (rv) phosphoprotein p is a multifunctional protein involved in viral rna synthesis and in counteracting host innate immune responses. we have previously shown that rv p gene expression levels can be regulated by using picornavirus internal ribosome entry site (ires) elements. here we exploited a particular feature of the foot-and-mouth disease virus (fmdv) ires, namely, preferential initiation at a downstream initiation codon, to address the role of n-terminally truncated rv pho ...201121397980
significantly improved rescue of rabies virus from cdna plasmids.the rescue of recombinant rabies virus (rv) from cloned cdna is an inefficient process because it relies on the de novo formation within cells of functional ribonucleoprotein (rnp) complexes from plasmid-expressed viral-like antigenome rnas and three helper proteins. in the standard rv reverse genetics systems, bacteriophage t7 rna polymerase drives the transcription of virus antigenome-like rnas containing three nonviral g residues at the 5'-end and a correct 3'-end generated by the autocatalyt ...201121397981
porcine teschovirus polioencephalomyelitis in western canada.beginning in 2002, a small number of pig farms in western canada began reporting 4-7-week-old pigs with bilateral hind-end paresis or paralysis. low numbers of pigs were affected, some died, most had to be euthanized, and those that survived had reduced weight gains and neurological deficits. necropsies revealed no gross lesions, but microscopic lesions consisted of a nonsuppurative polioencephalomyelitis, most severe in the brain stem and spinal cord. the lesions were most consistent with a vir ...201121398466
characterization of rabies virus isolated from a colony of eptesicus furinalis bats in brazil.some bat species have adapted to the expanding human population by acquiring the ability to roost in urban buildings, increasing the exposure risk for people and domestic animals, and consequently, the likelihood of transmitting rabies. three dead bats were found in the yard of a house in an urban area of jundiaí city in the state of são paulo in southeast brazil. two of the three bats tested positive for rabies, using fluorescent antibody and mouse inoculation techniques. a large colony of epte ...201121412617
antemortem diagnosis of human rabies in a veterinarian infected when handling a herbivore in minas gerais, brazil.the ministry of health's national human rabies control program advocates pre-exposure prophylaxis (pep) for professionals involved with animals that are at risk of contracting rabies. we report an antemortem and postmortem diagnosis of rabies in a veterinarian who became infected when handling herbivores with rabies. the antemortem diagnosis was carried out with a saliva sample and a biopsy of hair follicles using molecular biology techniques, while the postmortem diagnosis used a brain sample a ...201121412618
new method to produce equine antirabies immunoglobulin f(ab')2 fragments from crude plasma in high quality and yield.rabies is still a major cause of human deaths in several developing countries. according to the world health organization, administration of antirabies serum or antirabies immunoglobulin is recommended for patients who have experienced a category-iii exposure to rabies. improvement of antirabies immunoglobulin production is required to enhance safety and efficacy of the products. in this paper, a new method to produce equine antirabies immunoglobulin f(ab')(2) fragments from crude plasma is prop ...201121414404
delivery of sirna to the mouse brain by systemic injection of targeted exosomes.to realize the therapeutic potential of rna drugs, efficient, tissue-specific and nonimmunogenic delivery technologies must be developed. here we show that exosomes-endogenous nano-vesicles that transport rnas and proteins-can deliver short interfering (si)rna to the brain in mice. to reduce immunogenicity, we used self-derived dendritic cells for exosome production. targeting was achieved by engineering the dendritic cells to express lamp2b, an exosomal membrane protein, fused to the neuron-spe ...201121423189
recovery from and clearance of rabies virus in a domestic ferret.here we document the case of a domestic ferret (mustela putorius) that survived experimental inoculation with rabies virus of skunk origin. the ferret showed initial clinical signs of rabies (hindlimb paralysis) on day 81 after inoculation. the animal survived with paraplegia but otherwise was in an adequate nutritional state until the end of the observation period (pi day 181). at necropsy, no gross lesions were observed. microscopic lesions were found in sections of cerebrum and spinal cord. i ...201121439220
high-density baiting with onrab® rabies vaccine baits to control arctic-variant rabies in striped skunks in ontario, canada.the arctic variant of rabies virus has been maintained in striped skunks in small foci in southwestern ontario, canada, despite the control of the disease in red foxes. to control the disease in skunks, high-density baiting with onrab(®) oral rabies vaccine baits was conducted by air and by hand distribution of baits in the vicinity of skunk cases. during 2009, antibody prevalences in skunks were higher in areas baited at a density of 300 baits/km(2) and flight-line spacing of 0.25 km than at 0. ...201121441200
molecular characterization of indian rabies virus isolates by partial sequencing of nucleoprotein (n) and phosphoprotein (p) genes.rabies is endemic and an important zoonosis in india. there are very few reports available on molecular epidemiology of rabies virus of indian origin. in this study to know the dynamics of rabies virus, a total of 41 rabies positive brain samples from dogs, cats, domestic animals, wildlife, and humans from 11 states were subjected to rt-pcr amplification of n gene between nucleotide n521-n1262 (742 bp) and p gene between nucleotide p239-p750 (512 bp). the n gene could be amplified from 30, while ...201121452061
immunoperoxidase inhibition assay for rabies antibody detection.an immunoperoxidase inhibition assay (iia) for detection of rabies antibodies in human sera is described. diluted test sera are added to microplates with paraformaldehyde-fixed, cer cells infected with rabies virus. antibodies in test sera compete with a rabies polyclonal rabbit antiserum which was added subsequently. next, an anti-rabbit igg-peroxidase conjugate is added and the reaction developed by the addition of the substrate 3-amino-9-ethylcarbazole (aec). the performance of the assay was ...201121458492
antibody persistence, 32 years after post-exposure prophylaxis with human diploid cell rabies vaccine (hdcv).in 1975-1976 forty-five persons severely bitten by rabid wolves and dogs in iran were treated successfully against rabies with hdcv. in this study contact was made with 26 of 45 above persons, 32 years after their initial treatment and all had rabies neutralizing antibody ranging from 0.3 to 2.69 iu/ml of serum. of the 26 persons, 17 had received a booster dose of hdcv, 28 years ago and the remaining 9 persons, who had not received any booster since the initial treatment, were given one booster ...201121458608
establishment of a stable cho cell line with high level expression of recombinant porcine ifn-ß.a cho cell clone (cho-poifn-ß) with stable porcine ifn-ß expression under control of cmv promoter was selected under g418 pressure. in a 25cm(2) cell culture flask (5 ml culture medium), the cumulative protein yield of recombinant poifn-ß reached 2.3×10(6) iu/ml. this cells clone maintained stable expression for at least 20 generations even in the absence of g418 selection pressure. the expressed recombinant poifn-ß could induce the expression of porcine mx protein in pk15 cells, and activate th ...201121459017
[construction and detection the bioactivity of human anti-rabies virus scdsfv].the purpose of this study is to produce new antibody molecules to neutralize the rabies virus specifically by the way of constructing and expressing the human anti-rabies virus scdsfv (disulfide stabilized single chain antibody) gene, and characterizing its bioactivity.201121465795
molecular epidemiology of rabies virus circulating in south korea, 1998-2010.we analyzed the nucleotide sequences of the g-l (glycoprotein-large protein) intergenic non-coding region of 33 strains of the rabies virus (rabv) isolated in south korea in 1998-2010 and compared the sequences with those of previously reported non-korean strains. the similarities of the nucleotide sequences of the g-l region among all korean rabv isolates ranged from 97.1 to 100%. based on the phylogenetic analysis of the g-l region, the korean rabv isolates were classified into three distinct ...201121467756
rabies diagnosis and serology in bats from the state of são paulo, brazil.bats are one of the most important reservoirs and vectors of the rabies virus in the world.201121468481
one-step protocol for amplification of near full-length cdna of the rabies virus genome.full-length genome sequencing of the rabies virus is not a routine laboratory procedure. to understand fully the epidemiology, genetic variation and evolution of the rabies virus, full-length viral genomes need to be obtained. for rabies virus studies, cdna synthesis is usually performed using nonspecific oligonucleotides followed by cloning. when specific primers are used, the cdna obtained is only partial and is limited to the coding regions. therefore, the development of methods for synthesiz ...201121473884
evolutionary history of rabies in ghana.rabies virus (rabv) is enzootic throughout africa, with the domestic dog (canis familiaris) being the principal vector. dog rabies is estimated to cause 24,000 human deaths per year in africa, however, this estimate is still considered to be conservative. two sub-saharan african rabv lineages have been detected in west africa. lineage 2 is present throughout west africa, whereas africa 1a dominates in northern and eastern africa, but has been detected in nigeria and gabon, and africa 1b was prev ...201121483707
llama-derived single domain antibodies to build multivalent, superpotent and broadened neutralizing anti-viral molecules.for efficient prevention of viral infections and cross protection, simultaneous targeting of multiple viral epitopes is a powerful strategy. llama heavy chain antibody fragments (vhh) against the trimeric envelope proteins of respiratory syncytial virus (fusion protein), rabies virus (glycoprotein) and h5n1 influenza (hemagglutinin 5) were selected from llama derived immune libraries by phage display. neutralizing vhh recognizing different epitopes in the receptor binding sites on the spikes wit ...201121483777
human rabies encephalitis prevention and treatment: progress since pasteur's discovery.rabies remains one of the most ancient and deadly of human infectious diseases. this viral zoonosis is transmitted principally by the saliva of infected dogs, inducing a form of encephalomyelitis that is almost invariably fatal. since the first implementation, by louis pasteur in 1885, of an efficient preventive post-exposure treatment, more effective protocols and safer products have been developed, providing almost 100% protection if administered early enough. however, this disease still repre ...201121488832
a brain-targeted rabies virus glycoprotein-disulfide linked pei nanocarrier for delivery of neurogenic microrna.recent advances in efficient microrna (mirna) delivery techniques using brain-targeted nanoparticles offer critical information for understanding the functional role of mirnas in vivo, and for supporting targeted gene therapy in terms of treating mirna-associated neurological diseases. here, we report the rabies virus glycoprotein (rvg)-labeled non-toxic sspei nanomaterials capable of neuron-specific mir-124a delivery to neuron in vivo. the rvg-labeled bpei-ss (rvg-sspei) nanocarrier showed less ...201121489620
human rabies--michigan, 2009.on november 9, 2009, a michigan hospital informed cdc of suspected rabies in a man aged 55 years. the patient reportedly had awakened with a bat on his arm 9 months earlier but had not sought medical evaluation. he went to a local emergency department (ed) on october 30 and soon after was hospitalized; he died 12 days later. on november 14, cdc confirmed infection with a rabies virus variant that commonly infects the silver-haired bat (lasionycteris noctivagans). this report summarizes the patie ...201121490561
first report of rabies infection in bats, molossus molossus, molossops neglectus and myotis riparius in the city of são paulo, state of são paulo, southeastern brazil.this paper presents the first report of rabies in three bat species, molossus molossus, molossops neglectus and myotis riparius in the city of são paulo, brazil.201121503551
re-assessment of direct fluorescent antibody negative brain tissues with a real-time pcr assay to detect the presence of raccoon rabies virus rna.the first report of the raccoon variant of rabies virus was in ontario, canada in 1999. as part of the control of this outbreak a point infection control (pic) strategy of trapping and euthanizing vector species was implemented. to evaluate whether this strategy was indeed removing diseased animals, rabies diagnosis was performed on these specimens. during a pic program conducted in 2003, 721 animals (raccoons, striped skunks and red foxes) were collected and euthanized and brain material from e ...201121514325
live attenuated rabies virus co-infected with street rabies virus protects animals against rabies.while current rabies post-exposure prophylaxis (pep) is highly effective, it is costly and the vaccination regimen is complicated, requiring both inactivated vaccines and immunoglobulins. a one-dose rabies vaccine for human pep remains a long-term goal. here, we describe development of a highly attenuated rabies virus erag3m, with a mutation in the glycoprotein (g) gene and a switch of the g gene with the matrix protein gene in the viral genome. after a one-dose intramuscular vaccination, the er ...201121514343
differential architecture of multisynaptic geniculo-cortical pathways to v4 and mt.parallel visual pathways in the primate brain known as the dorsal and ventral streams receive retinal inputs mainly through the magnocellular (m) and parvocellular (p) layers of the lateral geniculate nucleus. inputs from these layers terminate within distinct parts of layer 4c of v1 (visual area 1). due to the complexity of m- and p-derived neural connectivity in v1 and higher visual areas, the contributions of m and p inputs to the dorsal and ventral streams remain unclear. employing retrograd ...201121515714
ambivalent role of the innate immune response in rabies virus pathogenesis.the neurotropic rabies virus (rabv) has developed several evasive strategies including immunoevasion to successfully infect the nervous system (ns) and trigger a fatal encephalomyelitis. here, we show that lgp2 expression, a protein known either as a positive or negative regulator of the rig-i mediated-innate immune response, is restricted in the ns. we use a new transgenic mouse model (lgp2 tg) over-expressing lgp2 to impair rabv innate immune response and thus reveals the role of the rig-i-med ...201121525357
rabies in the eastern cape province of south africa--where are we going wrong?rabies is a growing problem in the eastern cape province of south africa. this study investigated dog ecology, vaccination coverage and rabies neutralising antibody levels in 203 randomly selected dogs within a local municipality in the former transkei area. responses to vaccination were also evaluated in 80 of these dogs. the population was remarkably uniform in size, breed and condition. slightly over 1/5th of the population was between 6 weeks and 1 year of age, while very few dogs reached 10 ...201021526734
[progress about genetic and variant study of rabies virus glycoprotein gene]. 201121528545
proteomic profiles of mouse neuro n2a cells infected with variant virulence of rabies viruses.we characterized the proteomes of murine n2a cells following infection with three rabies virus (rv) strains, characterized by distinct virulence phenotypes (i.e., virulent bd06, fixed cvs-11, and attenuated srv9 strains), and identified 35 changes to protein expression using twodimensional gel electrophoresis in whole-cell lysates. the annotated functions of these proteins are involved in various cytoskeletal, signal transduction, stress response, and metabolic processes. specifically, a-enolase ...201121532319
novel monoclonal antibodies that bind to wild and fixed rabies virus strains.ten monoclonal antibodies (mabs) against rabies virus, including igg3κ, igg2aκ, igmκ, and an igg2bκ isotype, were produced and characterized using neutralization, elisa, immunodot-blot, and immunofluorescence assays. mab 8d11, which recognized rabies virus glycoprotein, was found to neutralize rabies virus in vitro. when submitted to an immunofluorescence assay, seven mabs showed different reactivity against 35 brazilian rabies virus isolates. three mabs (lia 02, 3e6, and 9c7) only failed to rec ...201121536074
immunization of mice with the non-toxic hc50 domain of botulinum neurotoxin presented by rabies virus particles induces a strong immune response affording protection against high-dose botulinum neurotoxin challenge.we previously showed that rabies virus (rabv) virions are excellent vehicles for antigen presentation. here, a reverse genetic approach was applied to generate recombinant rabv that express a chimeric protein composed of the heavy chain carboxyterminal half (hc50) of botulinum neurotoxin type a (bont/a) and rabv glycoprotein (g). to promote surface expression and incorporation of hc50/a into rabv virions, the rabv glycoprotein (g) er translocation sequence, various fragments of rabv ectodomain ( ...201121549784
antiviral effect of edaphic cyanophytes on rabies and herpes-1 viruses.five cyanophyte species (amorphonostoc punctiforme, gloeocapsa turgidus, sphaeronostoc coeruleum, stratonostoc linckia f. spongiaeforme and synechococcus cedrorum) were isolated and identified from sandy egyptian soils. polysaccharides extracted from these species showed a pronounced antiviral activity against rabies and herpes-1 viruses represented by the absence of the characteristic cytopathic effects of these viruses. it was found that 100 μg polysaccharide/ml induced 100% inhibition of the ...201121555271
[the bats and rabies in the western region of the state of são paulo, brazil.]introduction: the polo da alta sorocabana laboratory in presidente prudente, sp, in partnership with other research institutions, conducted studies related to bats from the western region of the state of sao paulo, brazil. thus, certain situations were investigated, including: a) isolation of the rabies virus from 2006 to 2008; b) identification of respective antigenic variants; and c) characterization of daytime shelters of desmodus rotundus vampire bats. methods: samples for examination origin ...201121556491
inhibition of rabies virus propagation in mouse neuroblastoma cells by an intrabody against the viral phosphoprotein.rabies virus (rabv) is highly neurotropic and causes acute infection of the central nervous system. death can be averted by prompt post-exposure prophylaxis; however, after clinical symptoms appear, the mortality rate is almost 100% and no reliable treatment is available. in this study, we investigated whether intracellular immunization using single-chain variable fragments (scfvs) against rabv phosphoprotein (rabv-p) could inhibit rabv propagation in neuronal cells. of four scfv clones derived ...201121569799
active surveillance of bat rabies in france: a 5-year study (2004-2009).active surveillance of bats in france started in 2004 with an analysis of 18 of the 45 bat species reported in europe. rabies antibodies were detected in six indigenous species, mainly in eptesicus serotinus and myotis myotis, suggesting previous contact with the eblv-1 rabies virus. nineteen of the 177 tested bats were shown serologically positive in seven sites, particularly in central and south-western france. neither infectious viral particles nor viral genomes were detected in 173 and 308 t ...201121570221
molecular epidemiology of the rabies virus in slovenia 1994-2010.a molecular epidemiology study was performed on a selection of 30 rabies-positive brain samples collected between 1994 and 2010 in slovenia and originating from the red fox (n=19), badger (n=3), cattle (n=3), dog (n=2), cat (n=1), marten (n=1) and horse (n=1). based on the comparison of 1092 and 672 nucleotide sequences of nucleoprotein (n) and partial glycoprotein (g) gene regions, a low genetic diversity of the circulating strains was detected, but both phylogenetic trees were consistent with ...201121571453
characterization of a human antibody fragment fab and its calcium phosphate nanoparticles that inhibit rabies virus infection with vaccine.recombinant antibody phage display technology has been used to mimic many aspects of the processes that govern the generation and selection of high-affinity natural human antibodies in the human immune system, especially for infectious disease prophylaxis. an anti-rabies virus immunized phage-display fab library was constructed from peripheral blood lymphocytes from vaccinated volunteers. the immunized antibody library, with a diversity of 6.7×10(8), was used to select and produce antibodies tha ...201121573024
clinical and epidemiological features of human rabies cases in the philippines: a review from 1987 to 2006.background: rabies viral infection causes a fatal encephalomyelitis. in humans, classic features include hydrophobia, aerophobia, hypersalivation, agitation, and neurological symptoms. in the philippines, canine rabies contributes to a significant burden of human disease. methods: we retrospectively reviewed the medical records of 1839 patients admitted to san lazaro hospital, manila, philippines between 1987 and 2006, with a clinical diagnosis of rabies. we used the world health organization ca ...201121600825
comparative detection of rabies rna by nasba, real-time pcr and conventional pcr.five methods for the rna detection of rabies virus were directly compared in this study. these included conventional nucleic acid sequence-based amplification with electrochemiluminescence (nasba-ecl) assay, reverse transcription (rt)-heminested (hn) polymerase chain reaction (pcr) and taqman real-time rt-pcr using protocols as described previously. the first two methods have been routinely utilised for ante-mortem diagnosis of human rabies in thailand and other rabies-endemic asian and african ...201121600930
preface. 201121601038
rabies virus transcription and replication.rabies virus (rabv) is a negative-stranded rna virus. its genome is tightly encapsidated by the viral nucleoprotein (n) and this rna-n complex is the template for transcription and replication by the viral rna-dependent rna polymerase (l) and its cofactor, the phosphoprotein (p). we present molecular, structural, and cellular aspects of rabv transcription and replication. we first summarize the characteristics and molecular biology of both rna synthesis processes. we then discuss biochemical and ...201121601039
rabies virus assembly and budding.rabies virus (rabv) and other negative-strand rna viruses are the causes of serious diseases in humans and animals worldwide. assembly and budding are important late events in the replication cycles of these negative-strand rna viruses that have received much attention in the past decade. indeed, important insights into the molecular mechanisms by which rhabdoviral proteins usurp and/or interact with host proteins to promote efficient virion assembly and egress has greatly enhanced our understan ...201121601040
evasive strategies in rabies virus infection.rabies virus (rabv) is a strictly neurotropic virus that slowly propagates in the nervous system (ns) of the infected host from the site of entry (usually due to a bite) up to the site of exit (salivary glands). successful achievement of the virus cycle relies on the preservation of the neuronal network. once rabv has entered the ns, its progression is not interrupted either by destruction of the infected neurons or by the immune response, which are major host mechanisms for combating viral infe ...201121601041
rabies virus clearance from the central nervous system.rabies, a neurological disease associated with replication in central nervous system (cns) tissues of any of a number of rabies viruses endemic in nature, is generally fatal. prophylactic medical intervention is immune mediated and directed at preventing the spread of the virus from a peripheral site of exposure to the cns. while individuals rarely develop immune responses capable of clearing the virus from cns tissues, a variety of laboratory-attenuated rabies viruses are readily cleared from t ...201121601042
role of chemokines in rabies pathogenesis and protection.chemokines are a family of structurally related proteins that are expressed by almost all types of nucleated cells and mediate leukocyte activation and/or chemotactic activities. the role of chemokines in rabies pathogenesis and protection has only recently been investigated. expression of chemokines is induced by infection with laboratory-adapted, but not street, rabies viruses (rabvs), and it has been hypothesized that expression of chemokines is one of the mechanisms by which rabv is attenuat ...201121601043
interferon in rabies virus infection.rabies is among the longest known and most dangerous and feared infectious diseases for humans and animals and still is responsible for tenth of thousands of human deaths per year. the rabies virus (rabv) is a rather atypical member of the rhabdoviridae family as it has completely adapted during evolution to warm-blooded hosts and is directly transmitted between them, whereas most other rhabdoviruses are transmitted by insect vectors. the virus is also unique with respect to its extremely broad ...201121601044
the role of toll-like receptors in the induction of immune responses during rabies virus infection.the host response to infection generally begins with interactions between pathogen-associated molecular patterns common to a variety of infectious agents and reciprocal pattern-recognition receptors (prrs) expressed by cells of the innate immune system. the innate responses triggered by these interactions contribute to the early, innate control of infection as well as the induction of pathogen-specific adaptive immunity. the outcome of infection with wild-type rabies virus is particularly depend ...201121601045
role of oxidative stress in rabies virus infection.recent studies in an experimental model of rabies indicated that there are major structural changes in the brain involving neuronal processes that are associated with severe clinical disease. cultured adult mouse dorsal root ganglion (drg) neurons are a good in vitro model for studying the mechanisms involved in rabies virus-induced degeneration of neurites (axons) because, unlike other neuronal cell types, these neurons are fairly permissive to rabies virus infection. drg neurons infected with ...201121601046
rabies virus as a research tool and viral vaccine vector.until recently, single-stranded negative sense rna viruses (ssnsvs) were one of only a few important human viral pathogens, which could not be created from cdna. the inability to manipulate their genomes hindered their detailed genetic analysis. a key paper from conzelmann's laboratory in 1994 changed this with the publication of a method to recover rabies virus (rabv) from cdna. this discovery not only dramatically changed the broader field of ssnsv biology but also opened a whole new avenue fo ...201121601047
rabies virus as a transneuronal tracer of neuronal connections.powerful transneuronal tracing technologies exploit the ability of some neurotropic viruses to travel across neuronal pathways and to function as self-amplifying markers. rabies virus is the only viral tracer that is entirely specific, as it propagates exclusively between connected neurons by strictly unidirectional (retrograde) transneuronal transfer, allowing for the stepwise identification of neuronal connections of progressively higher order. transneuronal tracing studies in primates and rod ...201121601048
bats and lyssaviruses.numerous bat species have been identified as important reservoirs of zoonotic viral pathogens. rabies and rabies-related viruses constitute one of the most important viral zoonoses and pose a significant threat to public health across the globe. whereas rabies virus (rabv) appears to be restricted to bats of the new world, related lyssavirus species have not been detected in the americas and have only been detected in bat populations across africa, eurasia, and australia. currently, 11 distinct ...201121601050
neuroimaging in rabies.rabies remains a virtually incurable disease once symptoms develop. neuroimaging studies demonstrate lesions in the different parts of the neuroaxis, even before brain symptoms are evident. these abnormalities have been detailed in both rabies virus-infected humans and dogs with magnetic resonance imaging (mri). mri disturbances were similar in both forms (furious or paralytic) in human rabies; however, they were more pronounced in paralytic than in furious rabies virus-infected dogs in which ex ...201121601052
rabies virus infection and micrornas.endogenous rna-silencing mechanisms have been shown to play a role in regulating viral and host processes during the course of infection. such interactive processes may involve host cellular and/or viral-encoded micrornas (mirnas). rabies is unique not only in terms of its invariably fatal course once disease signs develop, but it also has a variable incubation period (eclipse phase). it has been recently shown that cells or tissues of different origin have their own specific mirnas that, in the ...201121601053
design of future rabies biologics and antiviral drugs.in recent years, no major paradigm shifts have occurred in the utilization of new products for the prevention and control of rabies. development of new cost-effective rabies biologics and antiviral drugs is critical in continuing to prevent and reduce disease. current rabies vaccines are highly effective but have developed largely based on technical improvements in the vaccine industry. in the future, alternative approaches for improved vaccines, including novel avirulent rabies virus (rabv) vec ...201121601054
mathematical models for rabies.rabies virus and its associated host-pathogen population dynamics have proven a remarkable model system for developing mathematical models of infectious disease emergence and spread. beginning with simple susceptible-infectious-removed (sir) compartment models of fox rabies emergence and spread across western europe, mathematical models have now been developed to incorporate dynamics across heterogeneous landscapes, host demographic variation, and environmental stochasticity. model structures ra ...201121601056
understanding effects of barriers on the spread and control of rabies.this chapter reviews the evidence for the impact of natural and anthropogenic barriers on the spread of rabies using evidence mainly drawn from the epidemics of fox and raccoon variant rabies virus over the past 60 years in north america. those barriers have both directed and inhibited the spread of rabies and, at a regional scale, have been integrated with rabies control efforts in north america. few studies have been done, however, to examine how the texture (grain) and configuration of the ha ...201121601058
rabies research in resource-poor countries.many cost-benefit/effective rabies research projects need to be carried out in less-developed canine-endemic regions. among these are educational approaches directed at the public and governments. they would address effective primary wound care, availability, and proper use of vaccines and immunoglobulins, better reporting of rabies, final elimination of dangerous nerve tissue-derived vaccines, and the recognition that rabies is still expanding its geographic range. such efforts could also reduc ...201121601059
rabbit anti-rabies immunoglobulins production and evaluation.due to the disadvantages of human and equine rabies immunoglobulin, it is necessary to develop a substitute for hrig and erig, especially for those people living in the developing countries. because of higher affinity and lower immunogenicity of rabbit's immunoglobulins, anti-rabies immunoglobulins specific to rabies virus were produced in rabbits as a bioreactor, and had been characterized by elisa, affinity assay, immunofluorescence assay (ifa), immunocytochemistry, rapid fluorescent focus inh ...201121602780
monosynaptic inputs to erbb4 expressing inhibitory neurons in mouse primary somatosensory cortex. 201121618237
medical microbiologythe family rhabdoviridae consists of more than 100 single-stranded, negative-sense, nonsegmented viruses that infect a wide variety of hosts, including vertebrates, invertebrates, and plants. common to all members of the family is a distinctive rod- or bullet-shaped morphology. human pathogens of medical importance are found in the genera lyssavirus and vesiculovirus.only rabies virus, medically the most significant member of the genus lyssavirus, is reviewed in this chapter.199621413354
genetic tracking of the raccoon variant of rabies virus in eastern north america.to gain insight into the incursion of the raccoon variant of rabies into the raccoon population in three canadian provinces, a collection of 192 isolates of the raccoon rabies virus (rrv) strain was acquired from across its north american range and was genetically characterized. a 516-nucleotide segment of the non-coding region between the g and l protein open reading frames, corresponding to the most variable region of the rabies virus genome, was sequenced. this analysis identified 119 differe ...201121624778
[risks of transmitting rabies virus from captive domiciliary common marmoset (callithrix jacchus) to human beings, in the metropolitan region of fortaleza, state of ceará, brazil.] 201121625806
evaluation of water-in-oil-in-water multiple emulsion and microemulsion as potential adjuvants for immunization with rabies antigen.water-in-oil-in-water (w/o/w) multiple emulsions and microemulsions have been studied as potential candidates to be formulated as adjuvants. in this work their application as adjuvants for rabies virus immunization was studied. the humoral response, the effective dose 50 and histology for the developed formulations were evaluated in mice and compared with those from traditional adjuvants. the microemulsion and w/o/w multiple emulsion adjuvants developed were able to induce humoral response in mi ...201121627989
molecular diversity and evolutionary history of rabies virus strains circulating in the balkans.molecular studies of european classical rabies viruses (rabv) have revealed a number of geographically clustered lineages. to study the diversity of balkan rabv, partial nucleoprotein (n) gene sequences were analysed from a unique panel of isolates (n=210), collected from various hosts between 1972-2006. all of the balkan isolates grouped within the european / middle east lineage, with the majority most closely related to east european (ee) strains. a number of rabv from bosnia & herzegovina (bi ...201121632560
newcastle disease virus-vectored rabies vaccine is safe, highly immunogenic, and provides long-lasting protection in dogs and cats.effective, safe, and affordable rabies vaccines are still being sought. newcastle disease virus (ndv), an avian paramyxovirus, has shown promise as a vectored vaccine for mammals. here, we generated the recombinant avirulent ndv lasota strain expressing the rabies virus glycoprotein(rvg)and evaluated its potential to serve as a vaccine against rabies. the recombinant virus, rl-rvg, retained its high-growth property in chicken eggs, with titers of up to 10(9.8) eid(50)/ml of allantoic fluid. rvg ...201121632762
a unique transcription mode of rabies virus high egg passage-flury strain detected in the infected baby hamster kidney-21 cells.the transcription mode of rabies virus high egg passage-flury (hep) strain was examined and compared with that of evelyn rokitniki abelseth (era) strain by northern blot analysis using rabies virus gene-specific probes. the era strain was shown exclusively to produce monocistronic mrnas in transcription. while all combinations of multicisronic transcripts including five monocistronic mrnas were detected in the viral rna transcripts of hep strain. it was concluded that the unique transcription mo ...201121645051
development of recombinant rabies viruses vectors with gaussia luciferase reporter based on chinese vaccine strain ctn181.the recombinant rabies virus (rv) vectors encoding the secreted gene marker gaussia luciferase (gluc) were generated based on chinese vaccine strain ctn181. vectors included replication competent ctn-gluc, ctn/g(q333r)-gluc, in which the amino acid in position 333 of glycoprotein was mutated from glutamine (q) to arginine (r), and replication constrained ctnδg-gluc, in which the glycoprotein encoding gene (g) was deleted. the growth of recombinant rvs in transfected cells was confirmed through b ...201121645562
host and viral ecology determine bat rabies seasonality and maintenance.rabies is an acute viral infection that is typically fatal. most rabies modeling has focused on disease dynamics and control within terrestrial mammals (e.g., raccoons and foxes). as such, rabies in bats has been largely neglected until recently. because bats have been implicated as natural reservoirs for several emerging zoonotic viruses, including sars-like corona viruses, henipaviruses, and lyssaviruses, understanding how pathogens are maintained within a population becomes vital. unfortunate ...201121646516
possible origin of csf antibodies induced by intrathecal immunization and prophylactic effects against intracerebral rabies virus infection.intrathecal (it) immunization involves injecting antigens directly into the intraventricular or subarachnoid spaces, or brain, to induce antigen-specific antibodies (ab) in the cerebrospinal fluid (csf). in the present study, rabbits were immunized it with inactivated rabies virus to investigate the origins of csf ab. the time course of ab induction and tumor necrosis factor-alpha expression suggested the possibility that the csf ab originated in the serum. in addition, ab-producing cells infilt ...201121646749
amino acid substitution at position 95 in rabies virus matrix protein affects viral pathogenicity.we previously reported that rabies virus strain ce(nim), but not the parental ni-ce strain, killed mice after intracerebral inoculation. ce(nim) and ni-ce are genetically identical except for two amino acids at positions 29 and 95 in the m protein. in this study, to identify which residue determines the pathogenicity, we examined pathogenicities of two ni-ce mutants, ce(nim29) and ce(nim95), which were established by replacement of an amino acid residue at position 29 or 95 in the ni-ce m protei ...201121646750
efficient influenza b virus propagation due to deficient interferon-induced antiviral activity in mdck cells.influenza b virus infections are mainly restricted to humans, which is partially caused by the inability of influenza b virus ns1 protein to counteract the innate immune response of other species. however, for cell culture-based influenza vaccine production non-human cells, such as madin-darby canine kidney (mdck) cells, are commonly used. therefore, the impact of cellular pathogen defence mechanisms on influenza b virus propagation in mdck cells was analysed in this study. activation of the cel ...201121651940
is the skin sensitivity test required for administering equine rabies immunoglobulin?rabies immunoglobulins are life-saving in patients with severe exposure to rabies. despite the high degree of purification of equine rabies immunoglobulin (erig), the product inserts still recommend a skin sensitivity test before administration of this heterologous serum. a recent who recommendation states that there are no scientific grounds for performing a skin test before administering erig because testing does not predict reactions and it should be given irrespective of the result of the te ...201121668049
morphology of superior colliculus- and middle temporal area-projecting neurons in primate primary visual cortex.layers 5 and 6 of primate primary visual cortex (v1) harbor morphologically diverse cell groups that have cortico-cortical and cortico-subcortical projections. layer 6 middle temporal area (mt)-projecting neurons are particularly interesting, as they are the only deep-layer cortical neurons that provide both cortico-cortical feedforward inputs (to area mt) and cortico-subcortical feedback projections (to superior colliculus [sc]) (fries et al., 1985). however, due to limitations in anatomical tr ...201121674487
survival of a rabies patient. 201121813936
expression and solubilization of insect cell based rabies virus glycoprotein and assessment of its immunogenicity and protective efficacy in mice.rabies is a fatal zoonotic disease of serious public health and economic significance worldwide. rabies virus glycoprotein (rvg) has been the major target for subunit vaccine development since it harbors domains responsible for induction of virus neutralizing antibodies, infectivity and neurovirulence. the glycoprotein (g) was cloned using baculo virus expression vector system (bevs) and expressed in sf-9 cells. in order to obtain a soluble form of g suitable for experimenting in mice, eighteen ...201121813661
neuron-specific gene transfer through retrograde transport of lentiviral vector pseudotyped with a novel type of fusion envelope glycoprotein.the lentiviral vector system is used extensively in gene therapy trials for various neurological and neurodegenerative disorders. the vector system permits efficient and sustained gene expression in many cell types through integration of the transgene into the host cell genome. however, there is a significant issue on the therapeutic use of lentiviral vectors that transgene insertion may lead to tumorigenesis by altering the expression of proto-oncogenes adjacent to the integration sites. one us ...201121806473
the type i interferon response bridles rabies virus infection and reduces pathogenicity.rabies virus (rabv) is a neurotropic virus transmitted by the bite of an infected animal that triggers a fatal encephalomyelitis. during its migration in the nervous system (ns), rabv triggers an innate immune response, including a type i ifn response well known to limit viral infections. we showed that although the neuroinvasive rabv strain cvs-niv dampens type i ifn signaling by inhibiting irf3 phosphorylation and stat2 translocation, an early and transient type i ifn response is still trigger ...201121805057
characterization of last-order premotor interneurons by transneuronal tracing with rabies virus in the neonatal mouse spinal cord.we characterized the interneurons involved in the control of ankle extensor (triceps surae [ts] muscles) motoneurons (mns) in the lumbar enlargement of mouse neonates by retrograde transneuronal tracing using rabies virus (rv). examination of the kinetics of retrograde transneuronal transfer at sequential intervals post inoculation enabled to determine the time window during which only the first-order interneurons, i.e. interneurons likely monosynaptically connected to mns (last-order interneuro ...201121800300
three dimensional morphology of rabies virus studied by cryo-electron tomography.the rabies virus (rabv) continues to be a worldwide health problem. rabv contains a single-stranded rna genome that associates with the nucleoprotein n. the resulting ribonucleoprotein complex is surrounded by matrix protein m, lipid bilayer and glycoprotein g. rabv was reported to organize in bullet-like virions, but the role of each viral component in adopting this morphology is unclear. we present here a cryo-electron tomography study of rabv showing additional morphologies consisting in bull ...201121784158
recombinant canine parvovirus-like particles express foreign epitopes in silkworm pupae.the capsid structural protein vp2 of canine parvovirus (cpv) can self-assemble into highly organized virus-like particles (vlps) and retain major immunoreactivity. in this study, different recombinant baculoviruses that expressed varying fusion proteins of the cpv vp2 protein with the t cell determinant and/or the linear virus-neutralizing epitope of rabies virus (rv) were generated. infection with these baculoviruses changed bmn cell morphology and inhibited their proliferation as well as damag ...201121782359
an outbreak of sheep rabies in shanxi province, china.summarythis study describes an outbreak of rabies in a flock of 110 sheep in yangqu county, shanxi province, china, in 2010. the flock, housed in a cave being used as a sheepfold, was attacked by a rabid dog, which resulted in 36 deaths over the following 2 days from the crushing and trampling caused by panic, and some 15 further deaths from rabies 2 weeks later. rabies in the sheep was confirmed by the fluorescent antibody test (fat) and rt-pcr. rabies virus was isolated from the index dog brai ...201121781367
a universal real-time assay for the detection of lyssaviruses.rabies virus (rabv) is enzootic throughout most of the world. it is now widely accepted that rabv had its origins in bats. ten of the 11 lyssavirus species recognised, including rabv, have been isolated from bats. there is, however, a lack of understanding regarding both the ecology and host reservoirs of lyssaviruses. a real-time pcr assay for the detection of all lyssaviruses using universal primers would be beneficial for lyssavirus surveillance. it was shown that using sybr(®) green, a unive ...201121777619
emerging theme: cellular pdz proteins as common targets of pathogenic viruses.more than a decade ago three viral oncoproteins - adenovirus type 9 e4-orf1, human t-lymphotropic virus type 1 tax, and high-risk human papillomavirus e6 - were found to encode a related carboxyl-terminal pdz domain-binding motif (pbm) that mediates interactions with a select group of cellular pdz proteins. recent studies have shown that many other viruses also encode pbm-containing proteins that bind to cellular pdz proteins. interestingly, these recently recognized viruses include not only som ...201121775458
[temporal and spatial population dynamics of rabies virus isolates in china].in order to study phylogeography, population dynamics and molecular evolution of rabies viruses (rabvs) isolates from china, especially spatio-temporal dynamics, the timescale of rabvs evolution and its pattern of migration, we performed an extensive comparative analysis of rabv n gene sequence data, representing 167 isolates sampled from 20 provinces in a 78-year period (from 1931 through 2009). the available chinese isolates could be divided into two distinct clades:phylogroup clades i compris ...201121774248
inhibition of rabies virus multiplication by sirna delivered through adenoviral vector in vitro in bhk-21 cells and in vivo in mice.to evaluate antiviral potential of adenoviral vector-delivered small interfering rna (sirna) against rabies, recombinant, replication-defective adenoviral vectors (radv) encoding sirnas targeting rabies virus (rv) polymerase (l) and nucleoprotein (n) genes were developed. the sirnas were delivered as small hairpin rnas (shrnas) through these vectors. treatment of bhk-21 cells with radv expressing sirna targeting l gene (radv-l) and n gene (radv-n) (100 moi) and their subsequent infection with rv ...201121767857
persistence of rabies antibody 5 years after post-exposure prophylaxis with vero cell antirabies vaccine and antibody response to a single booster dose.objective this study was to investigate the antibody response, persistence of antibody for 5 years and the effect of booster dose after this interval methods from august 2005 to february 2011, a total of 195 patients were enrolled into our study due to animal bite. the essen intramuscular (im) regimen, which is recommended by the who for modern vaccines used in post-exposure treatment, was adopted in this study. blood samples were obtained on d0, d7, d14, d45, y1, y2, y3, y4, y5 and y5+d14. immu ...201121752947
therapeutic immune clearance of rabies virus from the cns.the long-held concept that rabies infection is lethal in humans once the causative rabies virus has reached the cns has been called into question by the recent survival of a number of patients with clinical rabies. studies in animal models provide insight into why survival from a rabies virus infection that has spread to the cns is possible and the immune mechanisms involved. in the cns, both innate mechanisms capable of inhibiting virus replication and the activity of infiltrating rabies virus- ...201121686076
g glycoprotein amino acid residues required for human monoclonal antibody rab1 neutralization are conserved in rabies virus street isolates.replacement of polyclonal anti-rabies immunoglobulin (rig) used in rabies post-exposure prophylaxis (pep) with a monoclonal antibody will eliminate cost and availability constraints that currently exist using rig in the developing world. the human monoclonal antibody rab1 has been shown to neutralize all rabies street isolates tested; however for the laboratory-adapted fixed strain, cvs-11, mutation in the g glycoprotein of amino acid 336 from asparagine (n) to aspartic acid (d) resulted in resi ...201121693135
identification of binding epitope for anti-rabies virus glycoprotein single-chain fv fragment fv57.single-chain fv fragment (scfv) of anti-rabies glycoprotein (g protein) has been recommended as a new agent for detecting and neutralizing lethal rabies virus. in this study, we constructed scfv that corresponded to the fv fragment of cr57, a monoclonal antibody against rabies virus, and called it fv57. despite its virus neutralization activity, fv57 may or may not recognize the same epitope as that recognized by cr57. to resolve this issue, the binding epitope of rabies virus g protein recogniz ...201121675946
parallel feedback pathways in visual cortex of cats revealed through a modified rabies virus.the visual cortex of cats is highly evolved. analogously to the brains of primates, large numbers of visual areas are arranged hierarchically and can be parsed into separate dorsal and ventral streams for object recognition and visuospatial representation. within early primate visual areas, v1 and v2, and to a lesser extent v3, the two streams are relatively segregated and relayed in parallel to higher order cortex, although there is some evidence suggesting an alignment of v2 and v3 to one stre ...201121826663
an evaluation of dog rabies control in limpopo province (south africa).summaryrabies is a prevalent and re-emerging disease in south africa particularly in rural areas with high human densities. outbreaks are frequently reported in the north and eastern parts of this country, probably an indication of inadequacy in the control of the disease. following the 2005/2006 outbreak in limpopo, we undertook an analysis of case surveillance data and genetically characterized 18 rabies viruses, all recovered from domestic dogs. although rabies prevalence gradually declined a ...201121733270
[rabies transmission through organ transplantation.]classic rabies is a progressive and lethal infectious disease of animals, which may be transmitted to humans. inter-human infections are extremely rare. the present case describes transmittal of rabies virus by lung transplantation from an infected donor. histologically, a lymphocytic encephalomyelitis with neuronal cytoplasmic inclusion bodies was found. immunohistochemically, rabies virus antigen was detected in the central, autonomous and peripheral nervous system. by means of electron micros ...201121732080
[phylogenetic analysis of rabies viruses isolated from animals in tokyo in the 1950s].molecular epidemiological analysis of 96 rabies viruses isolated from animals in tokyo in the 1950s involves japanese fixed virus, komatsugawa, takamen, and nishigahara strains. strains isolated in tokyo were divided into tokyo 1 and tokyo 2, and grouped into a worldwide distribution cluster differing from takamen and nishigahara. tokyo 1 was grouped into the same cluster as viruses isolated from united states west coast dogs in the 1930s and 1940s. tokyo 2 was grouped into the same cluster as t ...201121706842
human rabies from exposure to a vampire bat in mexico --- louisiana, 2010.in august 2010, cdc confirmed a case of rabies in a migrant farm worker, aged 19 years, hospitalized in louisiana with encephalitis. the man developed acute neurologic symptoms at the end of july, shortly after arriving in the united states from michoac+ín, mexico. despite supportive care, his condition deteriorated, and he died on august 21. antemortem diagnostic testing confirmed the diagnosis of rabies, and samples collected at autopsy were positive for a vampire bat rabies virus variant. the ...201121832976
improvement of the specificity of a pan-viral microarray by using genus-specific oligonucleotides and reduction of interference by host genomes.rapid detection of viral pathogens is crucial for antiviral therapy. high-density 60-70-mer oligonucleotide microarrays have been explored for broad detection of many viruses. however, relatively low specificity and the complex analytical processes are the major limitations when pan-viral oligonucleotide microarrays are used to detect viral pathogens. in this study, genus-specific oligonucleotides were used as probes and modified sample preparations were carried out to improve the specificity an ...201121739454
international interlaboratory trials on rabies diagnosis: an overview of results and variation in reference diagnosis techniques (fluorescent antibody test, rabies tissue culture infection test, mouse inoculation test) and molecular biology techniques.interlaboratory trials on rabies diagnosis were organised in 2009 and in 2010 by the european union reference laboratory (eurl) for rabies. in 2009, two panels of virus samples were sent to participating laboratories to compare results on reference diagnosis techniques and on rt-pcr. a single panel was sent in 2010 to test fat (fluorescent antibody test), rtcit (rabies tissue culture infection test) and rt-pcr techniques. the virus panels included the rabv, eblv-1, eblv-2 and ablv strains. resul ...201121703307
antibodies to cell surface proteins redirect intracellular trafficking pathways.antibody-mediated intracellular delivery of therapeutic agents has been considered for treatment of a variety of diseases. these approaches involve targeting cell-surface receptor proteins expressed by tumors or viral proteins expressed on infected cells. we examined the intracellular trafficking of a viral cell-surface-expressed protein, rabies g, with or without binding a specific antibody, arg1. we found that antibody binding shifts the native intracellular trafficking pathway of rabies g in ...201121819978
anterograde or retrograde transsynaptic labeling of cns neurons with vesicular stomatitis virus vectors.to understand how the nervous system processes information, a map of the connections among neurons would be of great benefit. here we describe the use of vesicular stomatitis virus (vsv) for tracing neuronal connections in vivo. we made vsv vectors that used glycoprotein (g) genes from several other viruses. the g protein from lymphocytic choriomeningitis virus endowed vsv with the ability to spread transsynaptically, specifically in an anterograde direction, whereas the rabies virus glycoprotei ...201121825165
Rabies-related knowledge and practices among persons at risk of bat exposures in Thailand.Rabies is a fatal encephalitis caused by lyssaviruses. Evidence of lyssavirus circulation has recently emerged in Southeast Asian bats. A cross-sectional study was conducted in Thailand to assess rabies-related knowledge and practices among persons regularly exposed to bats and bat habitats. The objectives were to identify deficiencies in rabies awareness, describe the occurrence of bat exposures, and explore factors associated with transdermal bat exposures.201121738801
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