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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
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
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
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
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
antibody response to vaccines for rhinotracheitis, caliciviral disease, panleukopenia, feline leukemia, and rabies in tigers (panthera tigris) and lions (panthera leo).this article presents the results of a study of captive tigers (panthera tigris) and lions (panthera leo) vaccinated with a recombinant vaccine against feline leukemia virus; an inactivated adjuvanted vaccine against rabies virus; and a multivalent modified live vaccine against feline herpesvirus, calicivirus, and panleukopenia virus. the aim of the study was to assess the immune response and safety of the vaccines and to compare the effects of the administration of single (1 ml) and double (2 m ...201222779227
antiretroviral therapy interruptions result in loss of protective humoral immunity to neoantigens in hiv-infected individuals.sustained antiretroviral therapy (art)-mediated viral suppression restores responses to vaccination in hiv-1-infected individuals. as art interruption occur frequently in resource-constrained settings, we studied their effects on the ability to mount humoral immune responses against a neoantigen.201222516873
a role for granulocyte-macrophage colony-stimulating factor in the regulation of cd8(+) t cell responses to rabies virus.inflammatory cytokines have a significant role in altering the innate and adaptive arms of immune responses. here, we analyzed the effect of gm-csf on a rabv-vaccine vector co-expressing hiv-1 gag. to this end, we immunized mice with rabv expressing hiv-1 gag and gm-csf and analyzed the primary and recall cd8(+) t cell responses. we observed a statistically significant increase in antigen presenting cells (apcs) in the spleen and draining lymph nodes in response to gm-csf. despite the increase i ...201222341782
endemic lagos bat virus infection in eidolon helvum.phylogenetic analyses suggest lyssaviruses, including rabies virus, originated from bats. however, the role of bats in the maintenance, transmission and evolution of lyssaviruses is poorly understood. a number of genetically diverse lyssaviruses are present in africa, including lagos bat virus (lbv). a high seroprevalence of antibodies against lbv was detected in eidolon helvum bats. longitudinal seroprevalence and age-specific seroprevalence data were analysed and capture-mark-recapture (cmr) a ...201222370126
in vitro and in vivo isolation and characterization of duvenhage virus.a fatal human case of duvenhage virus (duvv) infection in a dutch traveller who had returned from kenya was reported in 2007. she exhibited classical symptoms of rabies encephalitis with distinct pathological findings. in the present study we describe the isolation and characterization of duvv in vitro and its passage in balb/c mice. the virus proved to be neuroinvasive in both juvenile and adult mice, resulting in about 50% lethality upon peripheral infection. clinical signs in infected mice we ...201222654660
a replication-deficient rabies virus vaccine expressing ebola virus glycoprotein is highly attenuated for neurovirulence.we are developing inactivated and live-attenuated rabies virus (rabv) vaccines expressing ebola virus (ebov) glycoprotein for use in humans and endangered wildlife, respectively. here, we further characterize the pathogenesis of the live-attenuated rabv/ebov vaccine candidates in mice in an effort to define their growth properties and potential for safety. rabv vaccines expressing gp (rv-gp) or a replication-deficient derivative with a deletion of the rabv g gene (rvδg-gp) are both avirulent aft ...201222889613
further characterization of the immune response in mice to inactivated and live rabies vaccines expressing ebola virus glycoprotein.we have previously developed (a) replication-competent, (b) replication-deficient, and (c) chemically inactivated rabies virus (rabv) vaccines expressing ebola virus (ebov) glycoprotein (gp) that induce humoral immunity against each virus and confer protection from both lethal rabv and mouse-adapted ebov challenge in mice. here, we expand our investigation of the immunogenic properties of these bivalent vaccines in mice. both live and killed vaccines induced primary ebov gp-specific t-cells and ...201222884661
a strategy to simultaneously eradicate the natural reservoirs of rabies and ebola virus.the efficacy of a recombinant live-attenuated or chemically inactivated bivalent vaccine against rabies virus (rabv) and ebola virus (ebov) infection was evaluated in a lethal mouse model of infection. the vaccines were derived from the live-attenuated street alabama dufferin b19 rabv platform already approved for veterinary use, where intramuscular, intranasal and intraperitoneal administration of the recombinant vaccines were avirulent in adult mice. significant levels of serum rabv- and ebov- ...201222309665
vascular mineralization in the brain of horses.vascular mineralization (siderocalcinosis) in the brain of horses has been usually assumed to be an incidental age-related finding with no clinic significance. in the present study, eight 15-32-year-old horses of different breeds with cerebral siderocalcinosis were studied. four of these horses had acute and severe central nervous system clinical signs of unknown etiology, 2 horses had neurological signs of known cause, and 2 horses did not have neurological signs. gross examination of the brain ...201222529137
a novel disulfide-stabilized single-chain variable antibody fragment against rabies virus g protein with enhanced in vivo neutralizing potency.rabies is a fatal infectious disease requiring efficient protection provided by post-exposure prophylaxis (pep) with rabies immunoglobulin (rig). the single-chain fv fragment (scfv) is a small engineered antigen binding protein derived from antibody variable heavy (v(h)) and light (v(l)) chains. this novel antibody format may potentially replace the current application of rig to detect and neutralize rabies virus (rv). however, the broad use of scfvs is confined by their generally low stability. ...201222484084
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
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
[development and preliminary assessment of a recombinant canarypox virus as an antirabic vaccine candidate].development and preliminary assessment of a recombinant canarypox virus as an antirabic vaccine candidate. in argentina, rabies is limited to some northern provinces. availability of new vaccines abolishing the handling of the rabies virus and allowing disease control has regional and national strategic importance. vaccines based on recombinant poxviruses have been successfully used as antirabic vaccines worldwide. although these systems are not commercially available, the platform to obtain rec ...201222997764
exposure to selected pathogens in to selected pathogens in geoffroy's cats and domestic carnivores from central argentina.wild carnivores share a high percentage of parasites and viruses with closely related domestic carnivores. because of increased overlap and potential contact with domestic species, we conducted a retrospective serosurvey for 11 common carnivore pathogens in 40 geoffroy's cats (leopardus geoffroyi) sampled between 2000 and 2008 within or near two protected areas in central argentina (lihué calel national park, la pampa, and campos del tuyú national park, buenos aires), as well as five domestic ca ...201223060491
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
development of monoclonal antibodies suitable for rabies virus antibody and antigen detection.the control of an infectious viral disease as rabies is made easier by rapid and accurate diagnosis. successful rabies prophylaxis is dependent upon the active immunization with vaccine along with passive administration of rabies virus neutralizing antibodies which together clear the virus before widespread infection of central nervous system occurs. the present study aimed at the development of monoclonal antibodies (mabs) suitable for rabies virus antibody and antigen detection. for the produc ...201224293819
comparative proteomics analysis of mice lymphocytes in early stages of infection by different strains of rabies virus.the cns immune response to rabies virus has been shown to be influenced by virulence of the virus strains. there is no comprehensive report of the peripheral immune response against different strains of rabies virus. in this report we used a comparative proteome analysis to find the early events in the spleen lymphocytes of mice infected by a street strain and an attenuated strain of the rabies virus. differentially expressed proteins were identified which play important biological roles such as ...201224293818
[immune efficacy of rabies virus glycoprotein expressed by baculovirus vector].to construct a recombinant baculovirus expressing glycoprotein (gp) of rv srv9 strain and test the immunological efficacy in mice, open reading frame of rabies virus gp gene of srv9 strain was cloned into the shuttle vector bacmid to construct the recombinant shuttle plasmid bacmid-g and transfection was performed into s f9 cells with the recombinant shuttle plasmid. cpe appeared in cell cultures was identified by electronmicroscopy. western-blot, ifa and immunity tests in mice were performed to ...201223233923
isolation and identification of a novel rabies virus lineage in china with natural recombinant nucleoprotein gene.rabies virus (rabv) causes severe neurological disease and death. as an important mechanism for generating genetic diversity in viruses, homologous recombination can lead to the emergence of novel virus strains with increased virulence and changed host tropism. however, it is still unclear whether recombination plays a role in the evolution of rabv. in this study, we isolated and sequenced four circulating rabv strains in china. phylogenetic analyses identified a novel lineage of hybrid origin t ...201223226506
human macrophage and dendritic cell-specific silencing of high-mobility group protein b1 ameliorates sepsis in a humanized mouse model.hypersecretion of cytokines by innate immune cells is thought to initiate multiple organ failure in murine models of sepsis. whether human cytokine storm also plays a similar role is not clear. here, we show that human hematopoietic cells are required to induce sepsis-induced mortality following cecal ligation and puncture (clp) in the severely immunodeficient nonobese diabetic (nod)/scid/il2rγ(-/-) mice, and sirna treatment to inhibit hmgb1 release by human macrophages and dendritic cells drama ...201223213216
arctic-like rabies virus, bangladesh.arctic/arctic-like rabies virus group 2 spread into bangladesh ≈32 years ago. because rabies is endemic to and a major public health problem in this country, we characterized this virus group. its glycoprotein has 3 potential n-glycosylation sites that affect viral pathogenesis. diversity of rabies virus might have public health implications in bangladesh.201223171512
variable evolutionary routes to host establishment across repeated rabies virus host shifts among bats.determining the genetic pathways that viruses traverse to establish in new host species is crucial to predict the outcome of cross-species transmission but poorly understood for most host-virus systems. using sequences encoding 78% of the rabies virus genome, we explored the extent, repeatability and dynamic outcome of evolution associated with multiple host shifts among new world bats. episodic bursts of positive selection were detected in several viral proteins, including regions associated wi ...201223150575
complete genome sequence of a highly virulent rabies virus isolated from a rabid pig in south china.a virulent rabies virus (rabv) strain, gd-sh-01, was isolated from brain tissue of a rabid pig in china. this report describes the first complete genome sequence of a swine-origin rabv strain, and this information will provide important insights into the transmission cycle and genetic diversity of rabv from different hosts in china.201223087116
rabies virus vaccines: is there a need for a pan-lyssavirus vaccine?all members of the lyssavirus genus are capable of causing disease that invariably results in death following the development of clinical symptoms. the recent detection of several novel lyssavirus species across the globe, in different animal species, has demonstrated that the lyssavirus genus contains a greater degree of genetic and antigenic variation than previously suspected. the divergence of species within the genus has led to a differentiation of lyssavirus isolates based on both antigeni ...201223084854
immune clearance of attenuated rabies virus results in neuronal survival with altered gene expression.rabies virus (rabv) is a highly neurotropic pathogen that typically leads to mortality of infected animals and humans. the precise etiology of rabies neuropathogenesis is unknown, though it is hypothesized to be due either to neuronal death or dysfunction. analysis of human brains post-mortem reveals surprisingly little tissue damage and neuropathology considering the dramatic clinical symptomology, supporting the neuronal dysfunction model. however, whether or not neurons survive infection and ...201223071441
mucosal adjuvants to improve wildlife rabies vaccination.raboral v-rg(®)a is a recombinant vaccine used in oral rabies vaccination (orv) programs for wildlife in the united states. vaccination rates for raccoons are substantially lower than vaccination rates for gray foxes and coyotes. research suggests that the low viscosity of the oral vaccine may preclude animals from receiving an effective dose when biting into the vaccine bait delivery system. we evaluated the possibility of using two benign compounds, chitosan and n,n,n-trimethylated chitosan (t ...201223060506
immune response and protection in raccoons (procyon lotor) following consumption of baits containing onrab®, a human adenovirus rabies glycoprotein recombinant vaccine.we investigated the immune response and protection conferred in raccoons (procyon lotor) following consumption of onrab(®) oral rabies vaccine baits. forty-two wild-caught, captive raccoons were each offered an onrab vaccine bait; 21 controls received no vaccine baits. blood samples collected from all raccoons before treatment, and each week posttreatment for 16 wk, were assessed for the presence of rabies virus antibody. in the bait group, an individual was considered to have responded to vacci ...201223060502
oral rabies vaccination of raccoons and striped skunks with onrab® baits: multiple factors influence field immunogenicity.multiple control methods have been used in north america to manage the spread of rabies caused by the raccoon (procyon lotor) rabies virus variant (rrvv). recently, oral vaccination with onrab(®) vaccine baits, which contain an adenovirus rabies glycoprotein recombinant, has been made available as an additional tool for rabies control. our objectives were to estimate rabies antibody prevalence in wild-caught raccoons and striped skunks (mephitis mephitis), and identify factors influencing the pr ...201223060499
three-year duration of immunity in cats vaccinated with a canarypox-vectored recombinant rabies virus vaccine.despite the availability of efficacious vaccines for animals and humans, rabies is still a major zoonosis. prevention of rabies in dogs and cats is key for reducing the risk of transmission of this deadly disease to humans. most veterinary vaccines are adjuvanted inactivated vaccines and have been shown to provide one to four-year duration of immunity. in response to debates about the safety of adjuvanted vaccines in cats, a non-adjuvanted feline rabies vaccine with one-year duration of immunity ...201223059358
evaluation of a direct rapid immunohistochemical test (drit) for rapid diagnosis of rabies in animals and humans.presently the gold standard diagnostic technique for rabies is the direct immunofluorescence assay (dfa) which is very expensive and requires a high level of expertise. there is a need for more economical and user friendly tests, particularly for use in developing countries. we have established one such test called the direct rapid immunohistochemical test (drit) for diagnosis of rabies using brain tissue. the test is based on capture of rabies nucleoprotein (n) antigen in brain smears using a c ...201223055005
monosynaptic inputs to new neurons in the dentate gyrus.adult hippocampal neurogenesis is considered important for cognition. the integration of newborn dentate gyrus granule cells into the existing network is regulated by afferent neuronal activity of unspecified origin. here we combine rabies virus-mediated retrograde tracing with retroviral labelling of new granule cells (21, 30, 60, 90 days after injection) to selectively identify and quantify their monosynaptic inputs in vivo. our results show that newborn granule cells receive afferents from in ...201223033083
safety and pharmacokinetics of a human monoclonal antibody to rabies virus: a randomized, dose-escalation phase 1 study in adults.rabies is an essentially fatal disease that is preventable with the timely administration of post-exposure prophylaxis (pep). the high cost of pep, which includes vaccine and hyperimmune globulin, is an impediment to the goal of preventing rabies in the developing world. recently a recombinant human igg(1) anti-rabies monoclonal antibody (sii rmab) has been developed in india to replace serum-derived rabies immunoglobulin. the present study was conducted to demonstrate the safety of sii rmab and ...201223010601
expression, purification and characterization of a human single-chain fv antibody fragment fused with the fc of an igg1 targeting a rabies antigen in pichia pastoris.because the demand for rabies post exposure prophylaxis (pep) treatment has increased exponentially in recent years, the limited supply of human and equine rabies immunoglobulin (hrig and erig) has failed to provide an adequate amount of the required passive immune component in pep in countries where canine rabies is endemic. the replacement of hrig and erig with a potentially cheaper and efficacious alternative biological for the treatment of rabies in humans, therefore, remains a high priority ...201222982755
complete genome sequence of a street rabies virus from mexico.a canine rabies virus (rabv) has been used as a street rabies virus in laboratory investigations. its entire genome was sequenced and found to be closely related to that of canine rabv circulating in mexico. sequence comparison indicates that the virus is closely related to those in the "cosmopolitan" group, with high homology (89 to 93%) to clade i of rabies viruses. the virus is now termed dog rabies virus-mexico (drv-mexico).201222966186
complete genome sequence of a street rabies virus isolated from a rabid dog in china.a rabies virus (rabv) was isolated from a dog in anhui province, china, in 2008. the virus was designated drv-ah08. its entire genome was sequenced and found to be closely related to rabv recently isolated in china and other asian countries (homology of 87 to 98%) but distantly related to rabv in the "cosmopolitan" group (homology of 84 to 85%) in the clade i of rabv.201222966185
control of terrestrial animal rabies in anne arundel county, maryland, after oral vaccination of raccoons (1998-2007).to evaluate the effectiveness of an oral rabies vaccination (orv) project conducted from 1998 through 2007 in anne arundel county, md, for the control of rabies in terrestrial animals.201222947155
rabies surveillance in the united states during 2011.during 2011, 49 states and puerto rico reported 6,031 rabid animals and 6 human rabies cases to the cdc, representing a 1.9% decrease from the 6,153 rabid animals and 2 human cases reported in 2010. approximately 92% of reported rabid animals were wildlife. relative contributions by the major animal groups were as follows: 1,981 raccoons (32.8%), 1,627 skunks (27.0%), 1,380 bats (22.9%), 427 foxes (7.1%), 303 cats (5.0%), 65 cattle (1.1%), and 70 dogs (1.2%). compared with 2010, there was a subs ...201222947154
[analysis of the genetic differences in the nucleoprotein between rabies virus and its vaccine strains in guizhou province from year 2005 to 2010].this study was to explore the differences in the nucleoprotein gene between rabies virus (rabv) and its vaccine strains in guizhou province from year 2005 to 2010.201222943895
cxcl12 improves immune responses to neurotropic virus propagation in the cns by attracting antibody secreting cells.a previous study showed that increases in chemokine expression and recruitment of antibody secreting cells (ascs) in the cns after intracerebral immunization contributed to the suppression of a neurotropic virus. in this study, intracerebral chemokine injection was used to investigate the usefulness of chemokines for controlling neurotropic viruses. both cxcl12 and a cocktail chemokine (a mixture of cxcl9, 10, 12 and 13) attracted antigen-specific ascs more strongly than cxcl9, 10 and 13 in an i ...201222939585
current status of canine rabies in china.the number of human rabies cases acquired from dog bites constitutes a high proportion of the total rabies cases in china, although the number of human rabies cases has gradually decreased in recent years. the pivotal role of dogs in the spread of rabies indicates that controlling and preventing canine rabies could be a key step in eradicating human rabies in china. the primary aims of this review are to discuss the properties and pathogenesis of the rabies virus, the clinical signs and diagnosi ...201223122320
anatomical evidence for the involvement of medial cerebellar output from the interpositus nuclei in cognitive functions.although the cerebellar interpositus nuclei are known to be involved in cognitive functions, such as associative motor learning, no anatomical evidence has been available for this issue. here we used retrograde transneuronal transport of rabies virus to identify neurons in the cerebellar nuclei that project via the thalamus to area 46 of the prefrontal cortex of macaques in comparison with the projections to the primary motor cortex (m1). after rabies injections into area 46, many neurons in the ...201223112179
involvement of extraneural tissues and upregulation of inducible nitric oxide synthase after experimental infection with rabies virus in balb/c mice and lew/ssn rats.rabies virus can cause fatal encephalomyelitis, but the involvement of extraneural organs has not been well characterized. in this study, we investigated the histopathological changes and the distribution of viral antigens in extraneural organs after pathogenic rabies virus infection in mouse and rat models. in histopathological examination, classical viral encephalitis and rabies-specific negri body were observed in the brain. in addition to the central nervous system (cns), inflammatory respon ...201222924848
evaluation of cognitive learning, memory, psychomotor, immunologic, and retinal functions in healthy puppies fed foods fortified with docosahexaenoic acid-rich fish oil from 8 to 52 weeks of age.to assess effects of foods fortified with docosahexaenoic acid (dha)-rich fish oil on cognitive, memory, psychomotor, immunologic, and retinal function and other measures of development in healthy puppies.201222916855
progress on rnai-based molecular medicines.rna interference (rnai) is a promising strategy to suppress the expression of disease-relevant genes and induce post-transcriptional gene silencing. their simplicity and stability endow rnai with great advantages in molecular medicine. several rnai-based drugs are in various stages of clinical investigation. this review summarizes the ongoing research endeavors on rnai in molecular medicine, delivery systems for rnai-based drugs, and a compendium of rnai drugs in different stages of clinical dev ...201222915846
protective vaccine-induced cd4(+) t cell-independent b cell responses against rabies infection.a major goal in rabies virus (rv) research is to develop a single-dose postexposure prophylaxis (pep) that would simplify vaccination protocols, reduce costs associated with rabies prevention in humans, and save lives. live replication-deficient rv-based vaccines are emerging as promising single-dose vaccines to replace currently licensed inactivated rv-based vaccines. nonetheless, little is known about how effective b cells develop in response to live rv-based vaccination. understanding this fu ...201222896601
production and evaluation of a chromatographically purified vero cell rabies vaccine (pvrv) in china using microcarrier technology.china is a high population country with millions of animal bite cases every year; thus, it is necessary to explore and develop more effective and productive rabies vaccines for human use. to establish a safe, effective, inexpensive and high-yield rabies vaccine, a non-adjuvant purified vero cell rabies vaccine produced in the speeda pvrv microcarrier bioreactor was developed by liaoning chengda biology co. ltd. in china. this vaccine was produced using vero cells that were cultured in a microcar ...201222894963
interference with the pten-mast2 interaction by a viral protein leads to cellular relocalization of pten.pten (phosphatase and tensin homolog deleted on chromosome 10) and mast2 (microtubule-associated serine and threonine kinase 2) interact with each other through the pdz domain of mast2 (mast2-pdz) and the carboxyl-terminal (c-terminal) pdz domain-binding site (pdz-bs) of pten. these two proteins function as negative regulators of cell survival pathways, and silencing of either one promotes neuronal survival. in human neuroblastoma cells infected with rabies virus (rabv), the c-terminal pdz domai ...201222894835
adaptation of a chinese ferret badger strain of rabies virus to high-titered growth in bhk-21 cells for canine vaccine development.rabies virus strain jx08-45cc was derived from a chinese isolate (jx08-45) by serial passage in the bhk-21 cell line, reaching a titer of 10(8) tcid(50)/ml. jx08-45cc produced rabies in adult mice but was nonpathogenic in dogs after intramuscular injection. a comparison of the entire genomes of jx08-45 and jx08-45cc led to the identification of 17 nucleotide substitutions, resulting in seven amino acid changes in the mature g and l proteins. the immunogenicity of β-propiolactone-inactivated jx08 ...201222886183
small interfering rnas targeting the rabies virus nucleoprotein gene.rabies virus (rabv) infection continues to be a global threat to human and animal health, yet no curative therapy has been developed. rna interference (rnai) therapy, which silences expression of specific target genes, represents a promising approach for treating viral infections in mammalian hosts. we designed six small interfering (si)rnas (n473, n580, n783, n796, n799 and n1227) that target the conserved region of the rabv challenge virus standard (cvs)-11 strain nucleoprotein (n) gene. using ...201222884777
report on the international workshop on alternative methods for human and veterinary rabies vaccine testing: state of the science and planning the way forward.potency testing of most human and veterinary rabies vaccines requires vaccination of mice followed by a challenge test using an intracerebral injection of live rabies virus. niceatm, iccvam, and their international partners organized a workshop to review the availability and validation status of alternative methods that might reduce, refine, or replace the use of animals for rabies vaccine potency testing, and to identify research and development efforts to further advance alternative methods. w ...201222884673
[identification and sequential analysis on rabies virus isolated from a donkey].to identify and analyze the genetic characteristics of nucleoprotein (n) and glycoprotein (g) genes of rabies virus (rabv) isolated from a donkey in wuhan. n gene and g gene of the virus were compared with other representative street strains isolated around hubei areas as well as the vaccine strains used in china and abroad.201222883269
multisynaptic projections from the ventrolateral prefrontal cortex to the dorsal premotor cortex in macaques - anatomical substrate for conditional visuomotor behavior.lines of evidence indicate that both the ventrolateral prefrontal cortex (vlpfc) (areas 45/12) and dorsal premotor cortex (pmd) (rostral f2 in area 6) are crucially involved in conditional visuomotor behavior, in which it is required to determine an action based on an associated visual object. however, virtually no direct projections appear to exist between the vlpfc and pmd. in the present study, to elucidate possible multisynaptic networks linking the vlpfc to the pmd, we performed a series of ...201222882424
moving from rabies research to rabies control: lessons from india.despite the availability of effective interventions and public recognition of the severity of the problem, rabies continues to suffer neglect by programme planners in india and other low and middle income countries. we investigate whether this state of 'policy impasse' is due to, at least in part, the research community not catering to the information needs of the policy makers. methods #entitystartx00026;201222880139
organization of cerebral projections to identified cerebellar zones in the posterior cerebellum of the rat.the cerebrocerebellar connection makes use of two of the largest fiber tracts in the mammalian brain, i.e., the cerebral and medial cerebellar peduncles. neuroanatomical approaches aimed to elucidate the organization of this important connection have been hindered by its multisynaptic nature, the complex organization of its components, and the dependency of conventional tracers on precisely placed injections. to overcome these problems, we used rabies virus (rv) as a retrograde transneuronal tra ...201222875920
[neuronal linkage of the cerebral cortex and the striatum].the striatum is the major input station of the basal ganglia. it receives a wide variety of inputs from all areas of the cerebral cortex. in particular, there are several parallel loop circuits, such as the motor, oculomotor, dorsolateral prefrontal, lateral orbitofrontal, and anterior cingulate loops, linking the frontal lobe and the basal ganglia. with respect to the motor loop, the motor-related areas, including the primary motor cortex, supplementary motor area, dorsal and ventral premotor c ...201222868878
developments in rabies vaccines.the development of vaccines that prevent rabies has a long and distinguished history, with the earliest preceding modern understanding of viruses and the mechanisms of immune protection against disease. the correct application of inactivated tissue culture-derived vaccines is highly effective at preventing the development of rabies, and very few failures are recorded. furthermore, oral and parenteral vaccination is possible for wildlife, companion animals and livestock, again using inactivated t ...201222861358
evidence of rabies virus exposure among humans in the peruvian amazon.in may of 2010, two communities (truenococha and santa marta) reported to be at risk of vampire bat depredation were surveyed in the province datem del marañón in the loreto department of perú. risk factors for bat exposure included age less than or equal to 25 years and owning animals that had been bitten by bats. rabies virus neutralizing antibodies (rvnas) were detected in 11% (7 of 63) of human sera tested. rabies virus ribonucleoprotein (rnp) immunoglobulin g (igg) antibodies were detected ...201222855749
molecular characterization of the complete genome of a street rabies virus wh11 isolated from donkey in china.the complete genomic sequence of a rabies virus isolate wh11, isolated from brain tissue of a rabid donkey in china, was determined and compared with other rabies viruses. this is the first chinese street strain which was isolated from donkey and the entire length and organization of the virus was similar to that of other rabies viruses. multiple alignments of amino acid sequences of the nucleoprotein, phosphoprotein, matrix protein, glycoprotein, and large protein of wh11 with those of other ra ...201222836559
effect of hypothermic temperatures on production of rabies virus glycoprotein by recombinant drosophila melanogaster s2 cells cultured in suspension.aiming at maximizing the production of transmembrane rabies virus glycoprotein (rrvgp), the influence of hypothermic temperature on a recombinant drosophila melanogaster s2 cell culture in sf-900ii medium was investigated. cell growth and rrvgp production were assessed at 4 culture temperatures in schott flasks: 16, 20, 24 and 28 °c. the maximum specific growth rates μ(max) were, respectively: 0.009, 0.019, 0.038 and 0.035 h(-1), while the maximum rrvgp levels c(max)(rrvgp) were: 0.075, 2.973, 0 ...201222820340
molecular analysis of the mutational effects of thai street rabies virus with increased virulence in mice after passages in the bhk cell line.qs-bhk-p7, street rabies virus, after passages in the bhk cell line, had an in vitro phenotype that distinguished it from its parental virus. both viruses caused lethal infection in mice by central nervous system inoculation; however, only qs-bhk-p7 killed mice by the intramuscular route. we found four mutations, s23r and h424p in ectodomain of the glycoprotein (g), i1711 v in the polymerase genes, and another at the non-coding region between the phosphoprotein and matrix protein genes of qs-bhk ...201222777181
isolation of ssdna aptamers that inhibit rabies virus.aptamers, functional nucleic acids, capable of binding a variety of molecular targets with high affinity and specificity, have emerged as promising therapeutic agents. in this study, the cell surface-systematic evolution of ligands by exponential enrichment (cell-selex) strategy was used to generate dna aptamers which targeted to the intact rabies virus-infected live cells. through 35 iterative rounds of selection, five high-affinity single-stranded dna (ssdna) aptamers were generated by cell-se ...201222771543
induction of a protective immune response to rabies virus in sheep after oral immunization with transgenic maize, expressing the rabies virus glycoprotein.the introduction of exogenous genes into plants permits the development of a new generation of biological products, i.e., edible vaccines. cereals, especially maize, have been the systems of choice for the expression of antigenic proteins because the proteins can be expressed at high levels in the kernel and stored for prolonged periods without excessive deterioration. the utilization of plant-derived antigens for oral delivery provides an alternative strategy for the control of pathogens in ani ...201222749836
evaluation of a new serological technique for detecting rabies virus antibodies following vaccination.two major techniques are currently used to estimate rabies virus antibody values: neutralization assays, such as the rapid fluorescent focus inhibition test (rffit), and enzyme-linked immunosorbent assays (elisas). the rffit is considered the gold standard assay and has been used to assess the titer of rabies virus neutralizing antibodies for more than three decades. in the late 1970s, elisa began to be used to estimate the level of rabies virus antibody and has recently been used by some labora ...201222749835
targeted single-neuron infection with rabies virus for transneuronal multisynaptic tracing.the transynaptic and retrograde spread of rabies virus make it an efficient and robust transneuronal tracer, capable of revealing connectivity patterns of multisynaptic, neuronal circuits with great detail. current techniques begin by infecting many neurons simultaneously, from which higher-order neurons are then labeled sequentially in time. here we report on a method that can initially infect a single neuron-of-choice, allowing for greater precision and specificity of labeled circuits.201222749814
conservation of a unique mechanism of immune evasion across the lyssavirus genus.the evasion of host innate immunity by rabies virus, the prototype of the genus lyssavirus, depends on a unique mechanism of selective targeting of interferon-activated stat proteins by the viral phosphoprotein (p-protein). however, the immune evasion strategies of other lyssaviruses, including several lethal human pathogens, are unresolved. here, we show that this mechanism is conserved between the most distantly related members of the genus, providing important insights into the pathogenesis a ...201222740405
molecular inferences suggest multiple host shifts of rabies viruses from bats to mesocarnivores in arizona during 2001-2009.in nature, rabies virus (rabv; genus lyssavirus, family rhabdoviridae) represents an assemblage of phylogenetic lineages, associated with specific mammalian host species. although it is generally accepted that rabv evolved originally in bats and further shifted to carnivores, mechanisms of such host shifts are poorly understood, and examples are rarely present in surveillance data. outbreaks in carnivores caused by a rabv variant, associated with big brown bats, occurred repeatedly during 2001-2 ...201222737076
sufficient virus-neutralizing antibody in the central nerve system improves the survival of rabid rats.rabies is known to be lethal in human. treatment with passive immunity for the rabies is effective only when the patients have not shown the central nerve system (cns) signs. the blood-brain barrier (bbb) is a complex functional barrier that may compromise the therapeutic development in neurological diseases. the goal of this study is to determine the change of bbb integrity and to assess the therapeutic possibility of enhancing bbb permeability combined with passive immunity in the late stage o ...201222734518
preventative childhood vaccination to rabies.rabies is prevented by post-exposure vaccination with several doses of vaccine given over 4 - 14 weeks. in case of severe exposure, the first dose of vaccine is combined with passive transfer of a rabies virus-specific immunoglobulin preparation. preventative vaccination for rabies, also referred as pre-exposure vaccination, is reserved for humans at high risk. although available vaccines are efficacious in preventing disease, rabies still claims the lives of an estimated 55,000 humans residing ...201222724389
diversity of currently circulating rabies virus strains in croatia.sylvatic rabies has been present in croatia for more than three decades, with the red fox (vulpes vulpes) as the main reservoir. the present epidemic of sylvatic rabies in croatia started already in 1977 and in the past ten years the disease has become enzootic in the entire country and thus represents a considerable veterinary and public health threat. a genetic characterization and phylogenetic analysis of rabies virus isolates (rabv) from croatia was performed using panel of 32 selected rabie ...201222712423
interferon in lyssavirus infection.rabies is a zoonosis still claiming more than 50 000 human deaths per year. typically, human cases are due to infection with rabies virus, the prototype of the lyssavirus genus, but sporadic cases of rabies-like encephalitis caused by other lyssaviruses have been reported. in contrast to rabies virus, which has an extremely broad host range including many terrestrial warm-blooded animals, rabies-related viruses are associated predominantly with bats and rarely infect terrestrial species. in spit ...201222712418
tracing synaptic connectivity onto embryonic stem cell-derived neurons.transsynaptic circuit tracing using genetically modified rabies virus (rv) is an emerging technology for identifying synaptic connections between neurons. complementing this methodology, it is now possible to assay the basic molecular and cellular properties of neuronal lineages derived from embryonic stem cells (escs) in vitro, and these properties are under intense investigation toward devising cell replacement therapies. here, we report the generation of a novel mouse esc (mesc) line that har ...201222996827
a novel nuclear trafficking module regulates the nucleocytoplasmic localization of the rabies virus interferon antagonist, p protein.regulated nucleocytoplasmic transport of proteins is central to cellular function and dysfunction during processes such as viral infection. active protein trafficking into and out of the nucleus is dependent on the presence within cargo proteins of intrinsic specific modular signals for nuclear import (nuclear localization signals, nlss) and export (nuclear export signals, ness). rabies virus (rabv) phospho (p) protein, which is largely responsible for antagonising the host anti-viral response, ...201222700958
evaluation of a one week intradermal regimen for rabies post-exposure prophylaxis: results of a randomized, open label, active-controlled trial in healthy adult volunteers in india.the currently recommended intradermal regimen for post-exposure prophylaxis spreads over a month period which many times lead to low compliance from the patients. there is a need to introduce and evaluate short course regimens to overcome this problem. this study was conducted to evaluate the immunogenicity and safety of a "new one week intradermal regimen" for rabies post-exposure prophylaxis. a total of 80 healthy adult volunteers were enrolled and allocated randomly either to purified chick e ...201222699446
ecological and anthropogenic drivers of rabies exposure in vampire bats: implications for transmission and control.despite extensive culling of common vampire bats in latin america, lethal human rabies outbreaks transmitted by this species are increasingly recognized, and livestock rabies occurs with striking frequency. to identify the individual and population-level factors driving rabies virus (rv) transmission in vampire bats, we conducted a longitudinal capture-recapture study in 20 vampire bat colonies spanning four regions of peru. serology demonstrated the circulation of rv in vampire bats from all re ...201222696521
the full-length genome analysis of a street rabies virus strain isolated in yunnan province of china.the epidemic of rabies has rapidly increased and expanded in yunnan province in recent years. in order to further analyze and understand the etiological reasons for the rapid expansion of rabies in yunnan, a strain of rabies virus cyn1009d in yunnan was isolated, and the complete genomic sequencing was carried out, and the bioimfomative analysis on genes/encoded proteins and phylogeny with reference to sequences in genbank was performed. the complete genome of cyn1009d was 11923 nt in length and ...201222684475
molecular characterization of viral g gene in emerging and re-emerging areas of rabies in china, 2007 to 2011.in recent years (2007 to 2011), although the overall number of rabies cases in china has decreased, there is evidence of emerging or re-emerging cases in regions without previous rabies cases or with low incidence of rabies. to investigate the origin and the factors affecting the spread of rabies in china, specimens were collected from 2007 to 2011 from provinces with emerging and re-emerging cases and tested for the presence of the rabies virus. positive specimens were combined with sequences f ...201222684474
preparation and identification of anti-rabies virus monoclonal antibodies.to provide a foundation for the development of rapid and specific methods for the diagnosis of rabies virus infection, anti-rabies virus monoclonal antibodies were prepared and rabies virus nucleoprotein and human rabies virus vaccine strain (pv strain) were used as immunogens to immunize 6-8 week old female balb/c mice. spleen cells and sp2/0 myeloma cells were fused according to conventional methods: the monoclonal cell strains obtained were selected using the indirect immunofluorescence test; ...201222684471
whole-brain mapping of direct inputs to midbrain dopamine neurons.recent studies indicate that dopamine neurons in the ventral tegmental area (vta) and substantia nigra pars compacta (snc) convey distinct signals. to explore this difference, we comprehensively identified each area's monosynaptic inputs using the rabies virus. we show that dopamine neurons in both areas integrate inputs from a more diverse collection of areas than previously thought, including autonomic, motor, and somatosensory areas. snc and vta dopamine neurons receive contrasting excitatory ...201222681690
generation and characterization of neutralizing human recombinant antibodies against antigenic site ii of rabies virus glycoprotein.the currently recommended treatment for individuals exposed to rabies virus (rv) is post-exposure prophylaxis (pep) through the combined administration of rabies vaccine and rabies immune globulin (rig). human monoclonal antibodies (mabs) that neutralize rv offer an opportunity to replace rig for rabies pep. here, a combinatorial human fab library was constructed using antibody genes derived from the blood of rv-vaccinated donors. selections of this library against purified rv virions resulted i ...201222678022
molecular epidemiology of rabies in ukraine.to investigate the circulation of rabies virus in ukraine, 78 rabies virus isolates were acquired from 14 states in 2002 and 2008-2010 for characterization. partial sequences of nucleoprotein (359 nt) and glycoprotein (344 nt) genes were compared with those from neighbouring countries. the analysis identified 39 unique nucleoprotein genes and two geographically distinct rv variants belonging to the cosmopolitan lineage. the ukrainian samples were similar to the north-east european lineage (nee) ...201222661376
european pet travel: misleading information from veterinarians and government agencies.inter-country travel of companion animals provides an opportunity for introduction of zoonotic pathogens, such as rabies virus and echinococcus spp. regulations are in place to control this threat, but schengen agreements mean that border controls between some european countries are minimal, and animals may enter countries without any checks that they have been appropriately treated. veterinarians provide an important source of information for people intending to travel with their pets. we condu ...201222639949
detection of rabies viral rna by taqman real-time rt-pcr using non-neural specimens from dogs infected with rabies virus.to determine the burden of rabies in developing countries, a reliable and accurate diagnostic test for the examination of the brains of animals is needed. recently, the number of samples and carcasses submitted to rabies diagnostic units has been declining. methods for obtaining tissues from different regions of the brain are even more difficult, and direct florescent antibody examination may fail if the samples decomposed. the spread of rabies virus to peripheral non-nervous tissues starts earl ...201222626566
role of nuclear factor-κb in oxidative stress associated with rabies virus infection of adult rat dorsal root ganglion neurons.recent studies in an experimental model of rabies showed major structural changes in the brain involving neuronal processes that are associated with severe clinical disease. cultured adult rat dorsal root ganglion (drg) neurons infected with the challenge virus standard-11 strain of rabies virus (cvs) showed axonal swellings and immunostaining for 4-hydroxy-2-nonenal (4-hne), indicating evidence of lipid peroxidation associated with oxidative stress and reduced axonal growth compared to that of ...201222623795
susceptibility and lack of evidence for a viremic state of rabies in the night owl monkey, aotus nancymaae.rabies causes an acute fatal encephalomyelitis in most mammals following infection with rhabdovirus of the genus lyssavirus. little is known about rabies virus infection in species of new world non-human primates (nhp). to investigate the suitability of the owl monkey aotus nancymaae asissue sections examined were unremarkable for inflammation or other histologic signs of rabies a viable animal model for rabies virus candidate vaccine testing, we used clinical presentation, serology, viral isola ...201222612895
community survey after rabies outbreaks, flagstaff, arizona, usa.flagstaff, arizona, usa, experienced notable outbreaks of rabies caused by a bat rabies virus variant in carnivore species in 2001, 2004, 2005, 2008, and 2009. the most recent epizootic involved transmission among skunk and fox populations and human exposures. multiple, wide-ranging control efforts and health communications outreach were instituted in 2009, including a household survey given to community members. although the flagstaff community is knowledgeable about rabies and the ongoing outb ...201222607999
trends in national surveillance data for bat rabies in the united states: 2001-2009.rabies remains an important public health concern in the united states, with most human cases associated with bat rabies virus variants. cases of rabies virus (rv) infection in bats are widely distributed across the continental united states and elsewhere in the americas. in this retrospective study, data on bats submitted to state laboratories for rv diagnosis between 2001 and 2009 were analyzed to investigate epidemiological trends in the united states. season, region, and roosting habits were ...201222607069
segregated pathways carrying frontally derived top-down signals to visual areas mt and v4 in macaques.the bottom-up processing of visual information is strongly influenced by top-down signals, at least part of which is thought to be conveyed from the frontal cortex through the frontal eye field (fef) and the lateral intraparietal area (lip). here we investigated the architecture of multisynaptic pathways from the frontal cortex to the middle temporal area (mt) of the dorsal visual stream and visual area 4 (v4) of the ventral visual stream in macaques. in the first series of experiments, the retr ...201222593054
localization of rabies virus glycoprotein into the endoplasmic reticulum produces immunoprotective antigen.rabies virus surface glycoprotein (rabies g-protein) with (g+rs) and without (g-rs) endoplasmic reticulum retrieval signal was expressed and characterized in tobacco plants. transgenically expressed rabies g-protein was estimated at 0.015-0.38 % of total leaf protein. the relative migration of the rabies g-protein on sds-page was at the position, as anticipated for the viral coat protein (~66 kda). immunolocalization by confocal microscopy established that immunoprotective g+rs expressed in toba ...201222592449
high diversity of rabies viruses associated with insectivorous bats in argentina: presence of several independent enzootics.rabies is a fatal infection of the central nervous system primarily transmitted by rabid animal bites. rabies virus (rabv) circulates through two different epidemiological cycles: terrestrial and aerial, where dogs, foxes or skunks and bats, respectively, act as the most relevant reservoirs and/or vectors. it is widely accepted that insectivorous bats are not important vectors of rabv in argentina despite the great diversity of bat species and the extensive argentinean territory.201222590657
human rabies with initial manifestations that mimic acute brachial neuritis and guillain-barré syndrome.human rabies can be overlooked in places where this disease is now rare. its diagnosis is further confused by a negative history of exposure (cryptogenic rabies), by a guillain-barré syndrome (gbs) type of presentation, or by symptoms indicating another diagnosis, eg, acute brachial neuritis (abn).201222577299
the motor cortex communicates with the kidney.we used retrograde transneuronal transport of rabies virus from the rat kidney to identify the areas of the cerebral cortex that are potential sources of central commands for the neural regulation of this organ. our results indicate that multiple motor and nonmotor areas of the cerebral cortex contain output neurons that indirectly influence kidney function. these cortical areas include the primary motor cortex (m1), the rostromedial motor area (m2), the primary somatosensory cortex, the insula ...201222573695
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