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recombinant canine distemper virus serves as bivalent live vaccine against rabies and canine distemper.effective, safe, and affordable rabies vaccines are still being sought. attenuated live vaccine has been widely used to protect carnivores from canine distemper. in this study, we generated a recombinant canine distemper virus (cdv) vaccine strain, rcdv-rvg, expressing the rabies virus glycoprotein (rvg) by using reverse genetics. the recombinant virus rcdv-rvg retained growth properties similar to those of vector cdv in vero cell culture. animal studies demonstrated that rcdv-rvg was safe in mi ...201222698451
black-backed jackal exposure to rabies virus, canine distemper virus, and bacillus anthracis in etosha national park, namibia.canine distemper virus (cdv) and rabies virus (rabv) occur worldwide in wild carnivore and domestic dog populations and pose threats to wildlife conservation and public health. in etosha national park (enp), namibia, anthrax is endemic and generates carcasses frequently fed on by an unusually dense population of black-backed jackals (canis mesomelas). using serology, phylogenetic analyses (on samples obtained from february 2009-july 2010), and historical mortality records (1975-2011), we assesse ...201222493112
bacillus atrophaeus inactivated spores as a potential adjuvant for veterinary rabies vaccine.rabies is a viral encephalitis, nearly always fatal, but preventable through vaccines. rabid animal bite is the prime transmission act, while veterinary vaccination is one of the best strategies for rabies general prevention. aluminum compounds and saponin are the commercial adjuvants used for this vaccine nowadays. nevertheless, aluminum compounds can provoke undesired side effects and saponin has a narrow activity range without toxicity. b. atrophaeus inactivated spores (bais), with or without ...201222449426
a new rabies vaccine based on a recombinant orf virus (parapoxvirus) expressing the rabies virus glycoprotein.the present study describes the generation of a new orf virus (orfv) recombinant, d1701-v-rabg, expressing the rabies virus (rabv) glycoprotein that is correctly presented on the surface of infected cells without the need of replication or production of infectious recombinant virus. one single immunization with recombinant orfv can stimulate high rabv-specific virus-neutralizing antibody (vna) titers in mice, cats, and dogs, representing all nonpermissive hosts for the orfv vector. the protectiv ...201223175365
infection with street strain rabies virus induces modulation of the microrna profile of the mouse brain.rabies virus (rabv) causes a fatal infection of the central nervous systems (cns) of warm-blooded animals. once the clinical symptoms develop, rabies is almost invariably fatal. the mechanism of rabv pathogenesis remains poorly understood. recent studies have shown that microrna (mirna) plays an important role in the pathogenesis of viral infections. our recent findings have revealed that infection with laboratory-fixed rabies virus strain can induce modulation of the microrna profile of mouse b ...201222882874
rates of viral evolution are linked to host geography in bat rabies.rates of evolution span orders of magnitude among rna viruses with important implications for viral transmission and emergence. although the tempo of viral evolution is often ascribed to viral features such as mutation rates and transmission mode, these factors alone cannot explain variation among closely related viruses, where host biology might operate more strongly on viral evolution. here, we analyzed sequence data from hundreds of rabies viruses collected from bats throughout the americas t ...201222615575
molecular and cellular aspects of rhabdovirus entry.rhabdoviruses enter the cell via the endocytic pathway and subsequently fuse with a cellular membrane within the acidic environment of the endosome. both receptor recognition and membrane fusion are mediated by a single transmembrane viral glycoprotein (g). fusion is triggered via a low-ph induced structural rearrangement. g is an atypical fusion protein as there is a ph-dependent equilibrium between its pre- and post-fusion conformations. the elucidation of the atomic structures of these two co ...201222355455
imported human rabies - new jersey, 2011.on july 8, 2011, the new jersey department of health and senior services (njdhss) contacted cdc about possible rabies in a hospitalized haitian woman aged 73 years. rabies was included in the differential diagnosis because she had acute, progressive encephalitis of unknown etiology. no history of animal exposure had been reported at the time of hospitalization. on july 18, cdc confirmed rabies virus infection, later identified as a canine rabies virus variant present in haiti. the patient's neur ...201222217622
post-exposure treatment with the live-attenuated rabies virus (rv) vaccine trigas triggers the clearance of wild-type rv from the cns through the rapid induction of genes relevant to adaptive immunity in cns tissues.post-exposure treatment (pet) of wild-type rabies virus (rv)-infected mice with the live-attenuated triple glycoprotein rv variant (trigas) promotes survival but does not prevent the pathogenic rv from invading and replicating in the brain. successful pet is associated with the induction of a robust virus-neutralizing antibody response and clearance of the wild-type rv from brain tissues. comparison of the transcriptomes of normal mouse brain with those of wild-type rv-infected mice that had rec ...201222238315
the who rabies bulletin europe: a key source of information on rabies and a pivotal tool for surveillance and epidemiology.rabies is one of the most, if not the most, prominent and feared zoonotic diseases in the world and the world health organization (who) estimates that 55,000 people die of the disease every year. most of these deaths occur in asia and africa and are usually the result of dog-mediated rabies. in europe, the red fox is considered the main reservoir species for wildlife rabies caused by the rabies virus. besides foxes, bats have also been identified as a reservoir for european bat lyssaviruses in m ...201223520734
rabies virus and canine distemper virus in wild and domestic carnivores in northern kenya: are domestic dogs the reservoir?rabies virus (rv) and canine distemper virus (cdv) can cause significant mortality in wild carnivore populations, and rv threatens human lives. we investigated serological patterns of exposure to cdv and rv in domestic dogs (canis familiaris), african wild dogs (lycaon pictus), black-backed jackals (canis mesomelas), spotted hyenas (crocuta crocuta), striped hyenas (hyaena hyaena) and african lions (panthera leo), over a 10-year period, in a kenyan rangeland to assess the role domestic dogs may ...201223459924
pathobiology of rabies virus and the european bat lyssaviruses in experimentally infected mice.a comparison of the clinicopathology of european bat lyssavirus (eblv) types-1 and -2 and of rabies virus was undertaken. following inoculation of mice at a peripheral site with these viruses, clinical signs of rabies and distribution of virus antigen in the mouse brain were examined. the appearance of clinical signs of disease varied both within and across the different virus species, with variation in incubation periods and weight loss throughout disease progression. the distribution of viral ...201223274107
multisynaptic inputs from the medial temporal lobe to v4 in macaques.retrograde transsynaptic transport of rabies virus was employed to undertake the top-down projections from the medial temporal lobe (mtl) to visual area v4 of the occipitotemporal visual pathway in japanese monkeys (macaca fuscata). on day 3 after rabies injections into v4, neuronal labeling was observed prominently in the temporal lobe areas that have direct connections with v4, including area tf of the parahippocampal cortex. furthermore, conspicuous neuron labeling appeared disynaptically in ...201223272220
design of different strategies of multivalent dna-based vaccination against rabies and canine distemper in mice and dogs.during the vaccination campaigns, puppies younger than 3 months old are not targeted and remain unvaccinated for at least the first year of their lives. almost half of the reported rabid dogs are 6 months or younger. hence, we should recommend the vaccination against rabies of young puppies. unfortunately, owing to the exposure of puppies to infections with either canine parvovirus (cpv) or distemper virus (cdv) after the intervention of the vaccinators, owners are reluctant to vaccinate puppies ...201223270301
a novel rabies vaccine based on a recombinant parainfluenza virus 5 expressing rabies virus glycoprotein.untreated rabies virus (rabv) infection leads to death. vaccine and postexposure treatment have been effective in preventing rabv infection. however, due to cost, rabies vaccination and treatment have not been widely used in developing countries. there are 55,000 human death caused by rabies annually. an efficacious and cost-effective rabies vaccine is needed. parainfluenza virus 5 (piv5) is thought to contribute to kennel cough, and kennel cough vaccines containing live piv5 have been used in d ...201223269806
rabies virus glycoprotein is an important determinant for the induction of innate immune responses and the pathogenic mechanisms.our previous studies have suggested that street and fixed rabies viruses (rabvs) induce diseases in the mouse model via different mechanisms. in the present study, attempts were made to determine if it is the glycoprotein (g) that is responsible for the observed differences in the pathogenic mechanisms. to this end, an infectious clone from fixed virus b2c was established and used as a backbone for exchange of the g from street viruses. the rate of viral replication, expression of viral proteins ...201223265241
phylogeography of rabies virus isolated from herbivores and bats in the espírito santo state, brazil.rabies is enzootic in the state of espírito santo, brazil. every year, cattle and horses die from rabies that is transmitted by the vampire bat desmodus rotundus. this paper describes the spread of the rabies virus by the continuous diffusion model using relaxed random walks with beast software. forty-one (41) sequences of gene g from the rabies virus that was isolated from bats and domestic herbivores from several areas of the state between 2006 and 2010 were analyzed. the phylogenetic tree sho ...201223264105
process optimization and scale-up for production of rabies vaccine live adenovirus vector (adrg1.3).rabies virus is an important causative agent of disease resulting in an acute infection of the nervous system and death. although curable if treated in a timely manner, rabies remains a serious public health issue in developing countries, and the indigenous threat of rabies continues in developed countries because of wildlife reservoirs. control of rabies in wildlife is still an important challenge for governmental authorities. there are a number of rabies vaccines commercially available for con ...201222079076
contact with domestic dogs increases pathogen exposure in endangered african wild dogs (lycaon pictus).infectious diseases have contributed to the decline and local extinction of several wildlife species, including african wild dogs (lycaon pictus). mitigating such disease threats is challenging, partly because uncertainty about disease dynamics makes it difficult to identify the best management approaches. serious impacts on susceptible populations most frequently occur when generalist pathogens are maintained within populations of abundant (often domestic) "reservoir" hosts, and spill over into ...201222238695
Enhanced Expression of Rabies Virus Surface G-Protein in Escherichia coli using SUMO Fusion.Fusion systems are known to increase the expression of difficult to express recombinant proteins in soluble form to facilitate their purification. Rabies glycoprotein was also tough to express at sufficient level in soluble form in both E. coli and plant. The present work was aimed to over-express and purify this membrane protein from soluble extract of E. coli. Fusion of Small Ubiqutin like Modifier (SUMO) with rabies glycoprotein increased ~1.5 fold higher expression and ~3.0 fold solubility i ...201222134654
changes in microrna expression induced by rabies virus infection in mouse brains.micrornas (mirnas) are small rna (≈ 22 nt) molecules expressed endogenously in cells. they are involved in the regulation of gene expression. recently, evidence has shown that cellular mirnas have key regulatory roles in virus-host interactions. the rabies virus (rabv) causes a fatal infection of the central nervous systems (cns) of warm-blooded animals, yet its pathogenesis remains poorly understood. to gain more insight into the pathogenesis of rabv, a mirna microarray was performed as part of ...201222015383
Rabid dog illegally imported to France from Morocco, August 2011.In August 2011, a case of canine rabies was notified to the French veterinary services. The dog was a three-month-old puppy illegally imported from Morocco that presented behavioural changes on 1 August and was admitted to a veterinary clinic on 6 August. It died the following day and the body was shortly sent to the national reference centre where rabies was laboratory-confirmed on 11 August. Contact tracing and post-exposure treatment were initiated immediately.201121871230
Molecular epidemiology and a loop-mediated isothermal amplification method for diagnosis of infection with rabies virus in Zambia.The National Livestock Epidemiology and Information Center (NALEIC) in Zambia reported over 132 cases of canine rabies diagnosed by the direct fluorescent antibody test (DFAT) from 2004 to 2009. In this study, the lineage of rabies virus (RABV) in Zambia was determined by phylogenetic analysis of the nucleoprotein (N) and glycoprotein (G) gene sequences. Total RNA was extracted from 87-DFAT brain specimens out of which only 35 (40%) were positive on nested reverse transcription polymerase chain ...201121930165
preliminary evaluation of raboral v-rg® oral rabies vaccine in arctic foxes (vulpes lagopus).we tested the raboral v-rg® recombinant oral rabies vaccine for its response in arctic foxes (vulpes lagopus), the reservoir of rabies virus in the circumpolar north. the vaccine, which is currently the only licensed oral rabies vaccine in the united states, induced a strong antibody response and protected foxes against a challenge of 500,000 mouse intracerebral lethal dose 50% of an arctic rabies virus variant. however, one unvaccinated control fox survived challenge with rabies virus, either i ...201122102679
a novel neuroprotective therapy for parkinson's disease using a viral noncoding rna that protects mitochondrial complex i activity.parkinson's disease (pd) is a neurodegenerative disorder that results in the loss of nigrostriatal dopamine neurons. the etiology of this cell loss is unknown, but it involves abnormalities in mitochondrial function. in this study, we have demonstrated that the administration of a novel noncoding p137 rna, derived from the human cytomegaloviral β2.7 transcript, can prevent and rescue dopaminergic cell death in vitro and in animal models of pd by protecting mitochondrial complex i activity. furth ...201122184634
Enhanced pseudotyping efficiency of HIV-1 lentiviral vectors by a rabies/vesicular stomatitis virus chimeric envelope glycoprotein.Rabies virus glycoprotein (RVG) can pseudotype lentiviral vectors, although at a lower efficiency to that of vesicular stomatitis virus glycoprotein (VSVG). Transduction with VSVG-pseudotyped vectors of rodent central nervous system (CNS) leads to local neurotropic gene transfer, whereas with RVG-pseudotyped vectors additional disperse transduction of neurons located at distal efferent sites occurs via axonal retrograde transport. Attempts to produce high-titre RVG-pseudotyped lentiviral vectors ...201121900965
Intracerebral administration of recombinant rabies virus expressing GM-CSF prevents the development of rabies after infection with street virus.Recently it was found that prior immunization with recombinant rabies virus (RABV) expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) (LBNSE-GM-CSF) resulted in high innate/adaptive immune responses and protection against challenge with virulent RABV (Wen et al., JVI, 2011). In this study, the ability of LBNSE-GM-CSF to prevent animals from developing rabies was investigated in mice after infection with lethal doses of street RABV. It was found that intracerebral administration ...201121980450
subcellular trafficking in rhabdovirus infection and immune evasion: a novel target for therapeutics.vesicular stomatitis virus (vsv) and rabies virus (rabv) are the prototypic members of the rhabdovirus family. these viruses have a particularly broad host range, and despite the availability of vaccines, rabv still causes more than 50,000 human deaths a year. trafficking of the virion or viral particles is important at several stages of the replicative life cycle, including cellular entry, localization into the cytoplasmic inclusion bodies which primarily house the transcription and replication ...201122034934
Evidence for inter- and intra-clade recombinations in rabies virus.Homologous recombination is considered rare in negative-strand RNA viruses and has not been reported for rabies virus. In this study, full-length genomes of 44 rabies virus strains were analyzed for potential homologous recombination events. Phylogenetic analysis classified these strains into three clades. By applying six different recombination detection methods, one inter-clade and one intra-clade potential recombination events were identified with high confidence values. Software-predicted re ...201122041506
A Spatial Model to Forecast Raccoon Rabies Emergence.Abstract Although raccoons are widely distributed throughout North America, the raccoon rabies virus variant is enzootic only in the eastern United States, based on current surveillance data. This variant of rabies virus is now responsible for >60% of all cases of animal rabies reported in the United States each year. Ongoing national efforts via an oral rabies vaccination (ORV) program are aimed at preventing the spread of raccoon rabies. However, from an epidemiologic perspective, the relati ...201121995266
molecular characteristics and phylogenetic analysis of n gene of human derived rabies virus.to investigate the relationship between the molecular characteristics and phylogenetic evolution of rabies n gene.201122108333
laboratory surveillance of rabies in humans, domestic animals, and bats in madagascar from 2005 to 2010.background. rabies virus (rabv) has circulated in madagascar at least since the 19th century. objectives. to assess the circulation of lyssavirus in the island from 2005 to 2010. materials and methods. animal (including bats) and human samples were tested for rabv and other lyssavirus using antigen, ribonucleic acid (rna), and antibodies detection and virus isolation. results. half of the 437 domestic or tame wild terrestrial mammal brains tested were found rabv antigen positive, including 54% o ...201121991442
Public health implications of an outbreak of rabies in arctic foxes and reindeer in the Svalbard archipelago, Norway, September 2011. 201121996377
Peptides targeting the PDZ domain of PTPN4 are efficient inducers of glioblastoma cell death.PTPN4, a human tyrosine phosphatase, protects cells against apoptosis. This protection could be abrogated by targeting the PDZ domain of this phosphatase with a peptide mimicking the C-terminal sequence of the G protein of an attenuated rabies virus strain. Here, we demonstrate that glioblastoma death is triggered upon intracellular delivery of peptides, either from viral origin or from known endogenous ligands of PTPN4-PDZ, such as the C terminus sequence of the glutamate receptor subunit GluN2 ...201122000519
[Preparation and application of a colloidal gold strip to detect the rabies antibody].To develop a specific, rapid, and convenient immunochromatography assay (ICA) to detect the rabies antibody in clinical sample from immuned dogs by rabies vaccine. Colloidal gold particles labeled with purified rabies virus (CVS11) were used as the detector reagent. The staphylococcal protein A (SPA) and pured rabbit anti-rabies virus IgG were blotted on the test and control regions of nitrocellulose membrane. Then the strip was assembled with sample pad, absorbing pad, and dorsal shield. The as ...201121845847
[Development of SPA-ELISA for detection of antibodies against rabies virus based on expression of main antigenic determinant of nucleoprotein].To evaluate the effectiveness of rabies vaccination, we developed the SPA-ELISA method to detect the antibodies against rabies virus (RV) using the main antigenic determinant of nucleoprotein (RV N1) as antigen. The complete Nucleoprotein (N) gene and the partial N1 gene (1 000-1 353 bp) of RV Flury LEP strain were amplified using RT-PCR and PCR approaches. The two fragments were inserted into pGEX-6P-1 respectively. Then we transformed the recombinant plasmids into Escherichia coli BL21(DE3) st ...201122097803
exosome nanotechnology: an emerging paradigm shift in drug delivery: exploitation of exosome nanovesicles for systemic in vivo delivery of rnai heralds new horizons for drug delivery across biological barriers.the demonstration that dendritic cell (dc)-derived exosomes can be exploited for targeted rnai delivery to the brain after systemic injection provides the first proof-of-concept for the potential of these naturally occurring vesicles as vehicles of drug delivery. as well as being amenable to existing in vivo targeting strategies already in use for viruses and liposomes, this novel approach offers the added advantages of in vivo safety and low immunogenicity. fulfilment of the potential of exosom ...201121932222
immune response after rabies vaccine in a kidney transplant recipient.a 48-year-old male kidney-transplant recipient was bitten by a rabid dog. his immunosuppressive treatment consisted of cyclosporine 60 mg b.i.d., mycophenolate mofetil (mmf) 250 mg t.i.d., and prednisone 5 mg. after wound care, he received 5 doses of purified vero cell rabies vaccine on days 0, 3, 7, 14, and 28, and human rabies immunoglobulin, according to international guidelines. adequate levels of rabies virus neutralizing antibodies were observed after the administration of the third vaccin ...201121883758
drosophila melanogaster s2 cells for expression of heterologous genes: from gene cloning to bioprocess development.in the present review we discuss strategies that have been used for heterologous gene expression in drosophila melanogaster schneider 2 (s2) cells using plasmid vectors. since the growth of s2 cells is not dependent on anchorage to solid substrates, these cells can be easily cultured in suspension in large volumes. the factors that most affect the growth and gene expression of s2 cells, namely cell line, cell passage, inoculum concentration, culture medium, temperature, dissolved oxygen concentr ...201122079894
rabies in the arctic fox population, svalbard, norway.arctic foxes, 620 that were trapped and 22 found dead on svalbard, norway (1996-2004), as well as 10 foxes trapped in nenets, north-west russia (1999), were tested for rabies virus antigen in brain tissue by standard direct fluorescent antibody test. rabies antigen was found in two foxes from svalbard and in three from russia. blood samples from 515 of the fox carcasses were screened for rabies antibodies with negative result. our results, together with a previous screening (1980-1989, n=817) in ...201122102665
High vero cell density and rabies virus proliferation on fibracel disks versus cytodex-1 in spinner flask.To achieve higher titer of rabies virus higher density of host cells will need. In this study, capability of FibraCel disks packed in 500 mL spinner basket versus Cytodex-1 in 500 mL spinner flask was investigated for propagation of Vero cells and PV rabies virus proliferation. Minimal Essential Medium (MEM) + 10% Foetal Calf Serum (FCS) and Virus Production- Serum Free Medium (VP-SFM) +4 mM L-glutamine were used in growth phase and MEM+ 0.2% Bovine Serum Albumin (BSA) and VP-SFM were used in vi ...201121902056
Expression of rabies virus glycoprotein gene into eukaryotic system and determination of potential T-cell epitopes.The present study was undertaken to clone, express rabies virus glycoprotein (RVG) and to identify potential T-cell epitopes on it. RVG gene (1590 bp) was amplified using gene specific primers. The amplified product was cloned into pTZ57R/T cloning vector by TA cloning. RVG gene was subcloned into pcDNA3.1 (+) expression vector. In this study, cloning and expression of rabies virus glycoprotein gene was done under CMV promoter and an expression construct (pcDNA.RVG) was prepared and clones were ...201121870427
Treatment of rabies in the 21st century: curing the incurable?Despite the extreme case fatality attributable to rabies, reports of survivors provide a faint glimpse of a possibility of overcoming this deadly disease, even after clinical symptoms manifest. At present, no existing approach fulfills modern medical criteria for the optimal therapy of rabies. Until new efficacious antiviral compounds and optimized treatment protocols are developed, animal population management and vaccination of major reservoirs and vectors, minimization of the risk of viral ex ...201122004032
Nanobodies®: new ammunition to battle viruses.In 1989, a new type of antibody was identified, first in the sera of dromedaries and later also in all other species of the Camelidae family. These antibodies do not contain a light chain and also lack the first constant heavy domain. Today it is still unclear what the evolutionary advantage of such heavy chain-only antibodies could be. In sharp contrast, the broad applicability of the isolated variable antigen-binding domains (VHH) was rapidly recognized, especially for the development of thera ...201121939690
[Risk model to assess livestock rabies exposure in the state of São Paulo, Brazil].To propose a qualitative risk assessment model for the study of livestock exposure to rabies virus from the vampire bat Desmodus rotundus (antigenic variant 3) in the Paraíba do Sul river valley, state of São Paulo, Brazil.201122124696
Erratum to: Molecular characterization of Indian rabies virus isolates by partial sequencing of nucleoprotein (N) and phosphoprotein (P) genes. 201121922292
rabies surveillance in the united states during 2010.during 2010, 48 states and puerto rico reported 6,154 rabid animals and 2 human rabies cases to the cdc, representing an 8% decrease from the 6,690 rabid animals and 4 human cases reported in 2009. hawaii and mississippi did not report any laboratory-confirmed rabid animals during 2010. approximately 92% of reported rabid animals were wildlife. relative contributions by the major animal groups were as follows: 2,246 raccoons (36.5%), 1,448 skunks (23.5%), 1,430 bats (23.2%), 429 foxes (6.9%), 30 ...201121916759
Rabies in the critical care unit: diagnostic and therapeutic approaches.Worldwide, human rabies is prevalent where there is endemic dog rabies, but the disease may present unexpectedly in critical care units when suggestive clinical features have passed. In North America transmission from bats is most common and there is often no history of a bat bite or even contact with bats. Laboratory diagnostic evaluation for rabies includes serology plus skin biopsy, cerebrospinal fluid, and saliva specimens for rabies virus antigen and/or RNA detection. Rare patients have sur ...201121856570
immunogenicity studies in carnivores using a rabies virus construct with a site-directed deletion in the phosphoprotein.different approaches have been applied to develop highly attenuated rabies virus vaccines for oral vaccination of mesocarnivores. one prototype vaccine construct is sad dind1, which contains a deletion in the p-gene severely limiting the inhibition of type-1 interferon induction. immunogenicity studies in foxes and skunks were undertaken to investigate whether this highly attenuated vaccine would be more immunogenic than the parental sad b19 vaccine strain. in foxes, it was demonstrated that sad ...201121991446
pathology associated with a human case of rabies in the united kingdom caused by european bat lyssavirus type-2.human infection with the rabies-related virus european bat lyssavirus type-2 (eblv-2) has only been reported on two occasions. here we report the pathology observed within spinal cord and visceral tissues associated with eblv-2 infection for the first time. neuronal labelling with an anti-rabies nucleocapsid monoclonal antibody was observed and appeared indistinguishable from the labelling reported from human infection with rabies virus. © 2011 crown copyright. published by s. karger ag, basel.201122142887
Oral immunisation of mice with a recombinant rabies virus vaccine incorporating the heat-labile enterotoxin B subunit of Escherichia coli in an attenuated Salmonella strain.To investigate effective new rabies vaccines, a fusion protein consisting of the rabies virus (RV) glycoprotein and the heat-labile enterotoxin B subunit of Escherichia coli (LTB) was successfully constructed and delivered in a live attenuated Salmonella strain LH430. Mice were immunised with LH430 carrying pVAX1-G, pVAX1-G-LTB or pVAX1-ori-G-LTB. The antibody titres of mice immunised with oral LH430 carrying pVAX1-G-LTB or pVAX1-ori-G-LTB were significantly higher than those of pVAX1-G-immunise ...201122019192
Naturally Acquired Rabies Virus Infections in Wild-Caught Bats.Abstract The study of a zoonotic disease requires an understanding of the disease incidence in animal reservoirs. Rabies incidence in bats submitted to diagnostic laboratories does not accurately reflect the true incidence in wild bat populations as a bias exists for testing bats that have been in contact with humans or pets. This article details the rabies incidence in two species of bats collected from natural settings without such bias. In this study, brain smears from 0.6% and 2.5% of wild-c ...201121923271
[insertion of glycoprotein gene between p and m gene influences the pathogenicity of the rabies virus flury lep].to study the biological characteristics and pathogenicity of a recombinant rabies virus flury lep (low egg passage) that has two glycoprotein genes (g gene).201122097775
intracerebral delivery of small interfering rnas (sirnas) using adenoviral vector protects mice against lethal peripheral rabies challenge.to investigate the potential of rna interference (rnai) as antiviral agent against rabies, two small interfering rnas (sirnas) targeting rabies virus (rabv) nucleoprotein (n) and polymerase (l) genes were designed and evaluated. both sirnas knockdown or silenced the target rabv genes as evaluated in a plasmid based transient expression model. for efficient delivery, adenoviruses expressing the sirnas were constructed and antiviral potential of the delivered sirnas was investigated in bhk-21 cell ...201121864591
highly efficient method of preparing human catalytic antibody light chains and their biological characteristics.the ultimate goal of catalytic antibody research is to develop new patient therapies that use the advantages offered by human catalytic antibodies. the establishment of a high-throughput method for obtaining valuable candidate catalytic antibodies must be accelerated to achieve this objective. in this study, based on our concept that we can find antibody light chains with a high probability of success if they include a serine protease-like catalytic triad composed of ser, his, and asp on a varia ...201122205784
rabies in southeast brazil: a change in the epidemiological pattern.this epidemiological study was conducted using antigenic and genetic characterisation of rabies virus isolates obtained from different animal species in the southeast of brazil from 1993 to 2007. an alteration in the epidemiological profile was observed. one hundred two samples were tested using a panel of eight monoclonal antibodies, and 94 were genetically characterised by sequencing the nucleoprotein gene. from 1993 to 1997, antigenic variant 2 (agv-2), related to a rabies virus maintained in ...201122033596
raccoon dog rabies surveillance and post-vaccination monitoring in lithuania 2006 to 2010.abstract:201122085767
generation of a recombinant rabies flury lep virus carrying an additional g gene creates an improved seed virus for inactivated vaccine production.the rabies flury low egg passage virus (lep) has been widely used as a seed virus to generate inactive vaccine. here, we established a reverse genetic system for lep and generated a recombinant lep virus (rlep-g) that carries two identical g genes. this recombinant virus showed similar properties to those of lep with respect to in vitro growth, neurotropism index, and virulence in mice. rlep-g produced 4.3-fold more g protein than did lep in bhk-21 cells. the inactivated vaccine generated from r ...201121943337
gene expression analysis of host innate immune responses in the central nervous system following lethal cvs-11 infection in mice.the central nervous system (cns) tissue of mice infected with the cvs-11 strain of rabies virus (rabv) was subjected to gene expression analysis using microarray and canonical pathway analyses. genes associated with innate immunity as well as inflammatory responses were significantly up-regulated, corroborating with the previous findings obtained using attenuated viruses that did not induce a fatal outcome in infected mice. histopathological examination showed that neurons in the cerebellum ...201122116324
cerebellar vermis is a target of projections from the motor areas in the cerebral cortex.the cerebellum has a medial, cortico-nuclear zone consisting of the cerebellar vermis and the fastigial nucleus. functionally, this zone is concerned with whole-body posture and locomotion. the vermis classically is thought to be included within the "spinocerebellum" and to receive somatic sensory input from ascending spinal pathways. in contrast, the lateral zone of the cerebellum is included in the "cerebro-cerebellum" because it is densely interconnected with the cerebral cortex. here we repo ...201121911381
immunogenicity of simulated pcecv postexposure booster doses 1, 3, and 5 years after 2-dose and 3-dose primary rabies vaccination in schoolchildren.objectives. to assess the immunogenicity of intradermal (id) booster doses of purified chick embryo cell rabies vaccine (pcecv, rabipur) administered to thai schoolchildren one, three and five years after a primary id pre-exposure (prep) vaccination series. methods. in this follow-up study of a randomized, open-label, phase ii clinical trial, two simulated post-exposure booster doses of pcecv were administered on days 0 and 3 intradermally to 703 healthy schoolchildren, one, three or five years ...201121991438
molecular characterization of china rabies virus vaccine strain.abstract:201122093774
animal bites, active and reserve components, u.s. armed forces, 2001-2010.from 2001 to 2010, there were 20,522 diagnoses of animal bites among u.s. military members. of these, 643 (3.1%) were documented during medical encounters in combat theater. the majority of bites were "dog bites" and occurred more in males, soldiers, and those in infantry and law enforcement occupations. a small proportion of animal bites received documentation of exposure to or post-exposure prophylaxis for rabies virus. animal bite avoidance and rabies education should be reinforced before mem ...201121988341
recent emergence of the arctic rabies virus lineage.the rabies viruses that circulate in arctic countries and in much of northern and central asia are phylogenetically closely related and collectively referred to as the arctic/arctic-like (al) lineage. the emergence and spread of this lineage is of significant interest given that rabies remains a serious zoonotic disease in many parts of asia, especially in india where the prevalence of dog rabies leads to frequent human exposures and deaths. previous molecular epidemiological studies of rabies v ...201122100340
novel sylvatic rabies virus variant in endangered golden palm civet, sri lanka.information is scarce about sylvatic rabies virus in asia and about rabies in palm civets. we report a novel sylvatic rabies virus variant detected in a golden palm civet in sri lanka. evolutionary analysis suggests the virus diverged from canine rabies viruses in sri lanka in ≈1933 (range 1886-1963).201122172202
lentiviral gene transfer into the dorsal root ganglion of adult rats.lentivector-mediated gene delivery into the dorsal root ganglion (drg) is a promising method for exploring pain pathophysiology and for genetic treatment of chronic neuropathic pain. in this study, a series of modified lentivector particles with different cellular promoters, envelope glycoproteins, and viral accessory proteins were generated to evaluate the requirements for efficient transduction into neuronal cells in vitro and adult rat drg in vivo.201121861915
differentiation of the seven major lyssavirus species by oligonucleotide microarray.an oligonucleotide microarray, lyssachip, has been developed and verified as a highly specific diagnostic tool for differentiation of the 7 major lyssavirus species. as with conventional typing microarray methods, the lyssachip relies on sequence differences in the 371-nucleotide region coding of the nucleoprotein. this region was amplified using nested rt-pcr primers binding to the 7 major lyssaviruses. the lyssachip includes 57 pairs of species-typing and corresponding control oligonucleotide ...201122189108
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
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