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brain-targeted delivery of protein using chitosan- and rvg peptide-conjugated, pluronic-based nano-carrier.brain-targeted delivery of drug or imaging agent is hard to achieve efficiently due to the infiltrative nature of the blood-brain barrier (bbb). moreover, delivery of therapeutic proteins to brain tissue is further limited by the size and physic-chemical properties of proteins. in this work, we developed a chitosan-conjugated pluronic-based nano-carrier with a specific target peptide for the brain (rabies virus glycoprotein; rvg29) and applied for the protein delivery to the brain. the in-vivo b ...201323122677
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
viral tracing of genetically defined neural circuitry.classical methods for studying neuronal circuits are fairly low throughput. transsynaptic viruses, particularly the pseudorabies (prv) and rabies virus (rabv), and more recently vesicular stomatitis virus (vsv), for studying circuitry, is becoming increasingly popular. these higher throughput methods use viruses that transmit between neurons in either the anterograde or retrograde direction. recently, a modified rabv for monosynaptic retrograde tracing was developed. (figure 1a). in this method, ...201223117695
street rabies virus causes dendritic injury and f-actin depolymerization in the hippocampus.rabies is an acute viral infection of the central nervous system and is typically fatal in humans and animals; however, its pathogenesis remains poorly understood. in this study, the morphological changes of dendrites and dendritic spines in the ca1 region of the hippocampus were investigated in mice that were infected intracerebrally with an mrv strain of the street rabies virus. haematoxylin and eosin and fluorescence staining analysis of brain sections from the infected mice showed very few m ...201323114630
addition of a single n-glycan to street rabies virus glycoprotein enhances virus production.most street rabies virus g proteins have two n-glycosylation sites, i.e. asn(37) and asn(319), whereas additional sites are found in fixed (laboratory adapted) viruses. in this study, we performed a pseudotyped virus assay using g-deficient rabies virus and demonstrated that single-n-glycan additions to the g protein of street rabies virus strain 1088, which are found in adapted strains, enhanced virus production in neural and non-neural cell lines, while additions to asn(194) or asn(247) enhanc ...201323114627
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
interspecies protein substitution to investigate the role of the lyssavirus glycoprotein.european bat lyssaviruses type 1 (eblv-1) and type 2 (eblv-2) circulate within bat populations throughout europe and are capable of causing disease indistinguishable from that caused by classical rabies virus (rabv). however, the determinants of viral fitness and pathogenicity are poorly understood. full-length genome clones based on the highly attenuated, non-neuroinvasive, rabv vaccine strain (sad-b19) were constructed with the glycoprotein (g) of either sad-b19 (sn), of eblv-1 (sn-1) or eblv- ...201323100360
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
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
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
membrane and inclusion body targeting of lyssavirus matrix proteins.lyssavirus matrix proteins (m) support virus budding and have accessory functions that may contribute to host cell manipulation and adaptation to specific hosts. here, we show that rabies virus (rabv) and european bat lyssavirus type 1 (eblv-1) m proteins differ in targeting and accumulation at cellular membranes. in contrast to rabv m, eblv-1 m expressed from authentic eblv-1 or chimeric rabv accumulated at the golgi apparatus. chimeric m proteins revealed that golgi association depends on the ...201323046288
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
molecular characterisation of rabies virus strains in the republic of macedonia.rabies, a worldwide zoonosis, remains a public-health concern despite oral wildlife vaccination in europe. after a ten-year break, macedonia reported eight rabies cases in 2011-2012. two countries (serbia and bulgaria) bordering macedonia are reporting cases in domestic and wild animals. this report describes the genetic characterisation of eight isolates from macedonia compared with representative samples from neighbouring countries. all of the isolates tested belong to the eastern european gro ...201323001721
[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
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
dorsal area 46 is a major target of disynaptic projections from the medial temporal lobe.the medial temporal lobe (mtl) is responsible for various mnemonic functions, such as association/conjunction memory. the lateral prefrontal cortex (lpfc) also plays crucial roles in mnemonic functions and memory-based cognitive behaviors, for example, decision-making. therefore, it is considered that the mtl and lpfc connect with each other and cooperate for the control of cognitive behaviors. however, there exist very weak, if any, direct inputs from the mtl to the lpfc. employing retrograde t ...201322989578
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
metagenomic and metabolomic characterization of rabies encephalitis: new insights into the treatment of an ancient disease.rabies virus (rv) infection is a fatal nervous system disorder. we describe a patient who died of rabies despite a neuroprotective intervention. neuropathology showed neuronal loss with abundant rv antigen, genome, and negri bodies, accompanied by intense neuroinflammation, including by cd8(+) t lymphocyte infiltrates. deep sequencing and real-time reverse-transcription polymerase chain reaction revealed rna encoding a bat rv strain together with inflammatory gene induction. rv-infected brain de ...201322927447
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
[a new principle in the selection of vaccinal rabies virus based on quantitation of the expression of g protein, a major immunogen of rabies virus].the paper describes a new principle of the selection of the rabies virus vaccine strain era-cb20m based on quantitation of the expression of glycoprotein, a major immunogen of rabies virus. there is a correlation between the level of glycoprotein expression and that of vaccine virus attenuation. the application of the new principle for vaccine virus selection will permit a safer and more immunogenic rabies vaccine to be prepared.201622905428
rvg-mediated calpain2 gene silencing in the brain impairs learning and memory.in the central nervous system, two calpain isoforms are highly expressed: calpain1 and calpain2. here, we show for the first time that activation of the calpain isoform, calpain2, is a necessary event in hippocampal synaptic plasticity and in learning and memory. we developed a fluorescence resonance energy transfer-based animal model to monitor in vivo calpain activation in single cells and in real time. additionally, utilizing a novel rabies virus glycoprotein-chimeric peptide, which enabled t ...201322903378
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
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
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
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
[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
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
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
pyrosequencing of the rabies virus glycoprotein gene to demonstrate absence of vaccine-associated rabies cases following oral vaccination.replication competent vaccines have been used successfully for the control of terrestrial rabies, mainly in wildlife; however, these vaccine strains occasionally may induce rabies. in this study, a pyrosequencing protocol for the rapid identification of vaccine-associated rabies viruses was applied to the 2008-2011 italian epidemic. there was no evidence of vaccine-associated rabies cases following oral vaccination of foxes with the sag2 and sadb19 vaccine strains.201322841448
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
role of reverse transcriptase polymerase chain reaction for the diagnosis of human rabies.traditionally, rabies diagnosis is made by demonstration of rabies viral antigen by direct immunofluorescence (dif) and mouse inoculation test (mit). the present study was carried out to evaluate the role of reverse transcriptase-polymerase chain reaction (rt-pcr) in comparison with these conventional techniques for the diagnosis of rabies.022825603
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
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
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
bioeconomic modelling of raccoon rabies spread management impacts in quebec, canada.beginning in 2006, point infection control operations and aerial distribution of oral rabies vaccines along the us border were performed in quebec, canada, to control the potential spread of raccoon rabies. a benefit-cost analysis assessed the economic efficiency of this rabies control programme into the future. in this study, a mathematical simulation model was used to determine the potential spread of raccoon rabies from the 2006 index case, and incidence rates of human post-exposure prophylax ...201322709550
a novel nuclear trafficking module regulates the nucleocytoplasmic localization of the rabies virus interferon antagonist, p protein.regulated nucleocytoplasmic transport of proteins is central to cellular function and dysfunction during processes such as viral infection. active protein trafficking into and out of the nucleus is dependent on the presence within cargo proteins of intrinsic specific modular signals for nuclear import (nuclear localization signals, nlss) and export (nuclear export signals, ness). rabies virus (rabv) phospho (p) protein, which is largely responsible for antagonising the host anti-viral response, ...201222700958
evaluation of a one week intradermal regimen for rabies post-exposure prophylaxis: results of a randomized, open label, active-controlled trial in healthy adult volunteers in india.the currently recommended intradermal regimen for post-exposure prophylaxis spreads over a month period which many times lead to low compliance from the patients. there is a need to introduce and evaluate short course regimens to overcome this problem. this study was conducted to evaluate the immunogenicity and safety of a "new one week intradermal regimen" for rabies post-exposure prophylaxis. a total of 80 healthy adult volunteers were enrolled and allocated randomly either to purified chick e ...201222699446
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
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
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
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
a case study of rabies diagnosis from formalin-fixed brain material.rabies is caused by several lyssavirus species, a group of negative sense rna viruses. although rabies is preventable, it is often neglected particularly in developing countries in the face of many competing public and veterinary health priorities. epidemiological information based on laboratory-based surveillance data is critical to adequately strategise control and prevention plans. in this regard the fluorescent antibody test for rabies virus antigen in brain tissues is still considered the b ...201122616442
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
susceptibility and lack of evidence for a viremic state of rabies in the night owl monkey, aotus nancymaae.rabies causes an acute fatal encephalomyelitis in most mammals following infection with rhabdovirus of the genus lyssavirus. little is known about rabies virus infection in species of new world non-human primates (nhp). to investigate the suitability of the owl monkey aotus nancymaae asissue sections examined were unremarkable for inflammation or other histologic signs of rabies a viable animal model for rabies virus candidate vaccine testing, we used clinical presentation, serology, viral isola ...201222612895
community survey after rabies outbreaks, flagstaff, arizona, usa.flagstaff, arizona, usa, experienced notable outbreaks of rabies caused by a bat rabies virus variant in carnivore species in 2001, 2004, 2005, 2008, and 2009. the most recent epizootic involved transmission among skunk and fox populations and human exposures. multiple, wide-ranging control efforts and health communications outreach were instituted in 2009, including a household survey given to community members. although the flagstaff community is knowledgeable about rabies and the ongoing outb ...201222607999
trends in national surveillance data for bat rabies in the united states: 2001-2009.rabies remains an important public health concern in the united states, with most human cases associated with bat rabies virus variants. cases of rabies virus (rv) infection in bats are widely distributed across the continental united states and elsewhere in the americas. in this retrospective study, data on bats submitted to state laboratories for rv diagnosis between 2001 and 2009 were analyzed to investigate epidemiological trends in the united states. season, region, and roosting habits were ...201222607069
segregated pathways carrying frontally derived top-down signals to visual areas mt and v4 in macaques.the bottom-up processing of visual information is strongly influenced by top-down signals, at least part of which is thought to be conveyed from the frontal cortex through the frontal eye field (fef) and the lateral intraparietal area (lip). here we investigated the architecture of multisynaptic pathways from the frontal cortex to the middle temporal area (mt) of the dorsal visual stream and visual area 4 (v4) of the ventral visual stream in macaques. in the first series of experiments, the retr ...201222593054
localization of rabies virus glycoprotein into the endoplasmic reticulum produces immunoprotective antigen.rabies virus surface glycoprotein (rabies g-protein) with (g+rs) and without (g-rs) endoplasmic reticulum retrieval signal was expressed and characterized in tobacco plants. transgenically expressed rabies g-protein was estimated at 0.015-0.38 % of total leaf protein. the relative migration of the rabies g-protein on sds-page was at the position, as anticipated for the viral coat protein (~66 kda). immunolocalization by confocal microscopy established that immunoprotective g+rs expressed in toba ...201222592449
high diversity of rabies viruses associated with insectivorous bats in argentina: presence of several independent enzootics.rabies is a fatal infection of the central nervous system primarily transmitted by rabid animal bites. rabies virus (rabv) circulates through two different epidemiological cycles: terrestrial and aerial, where dogs, foxes or skunks and bats, respectively, act as the most relevant reservoirs and/or vectors. it is widely accepted that insectivorous bats are not important vectors of rabv in argentina despite the great diversity of bat species and the extensive argentinean territory.201222590657
human rabies with initial manifestations that mimic acute brachial neuritis and guillain-barré syndrome.human rabies can be overlooked in places where this disease is now rare. its diagnosis is further confused by a negative history of exposure (cryptogenic rabies), by a guillain-barré syndrome (gbs) type of presentation, or by symptoms indicating another diagnosis, eg, acute brachial neuritis (abn).201222577299
the motor cortex communicates with the kidney.we used retrograde transneuronal transport of rabies virus from the rat kidney to identify the areas of the cerebral cortex that are potential sources of central commands for the neural regulation of this organ. our results indicate that multiple motor and nonmotor areas of the cerebral cortex contain output neurons that indirectly influence kidney function. these cortical areas include the primary motor cortex (m1), the rostromedial motor area (m2), the primary somatosensory cortex, the insula ...201222573695
new introduction and spread of rabies among dog population in bangui.rabies is endemic in the central african republic (car) and a neglected enzootic disease which represents a serious public health problem. before april 2009, rabies was not a notifiable disease in car. vaccination of animals is expensive and not commonly done. in 2005, none rabies case was recorded in bangui. to understand how rabies was introduced and propagated in the city of bangui from 2006 to 2008, we analyzed samplings of dog brain as well as reviewed the records of dog owners. a total of ...201222569561
the spatial and temporal dynamics of rabies in china.recent years have seen a rapid increase in the number of rabies cases in china and an expansion in the geographic distribution of the virus. in spite of the seriousness of the outbreak and increasing number of fatalities, little is known about the phylogeography of the disease in china. in this study, we report an analysis of a set of nucleocapsid sequences consisting of samples collected through the trial chinese national surveillance system as well as publicly available sequences. this sequenc ...201222563518
six fatal cases of classical rabies virus without biting incidents, iran 1990-2010.rabies is an endemic fatal zoonotic disease, commonly transmitted to humans through contact (bites and scratches) with infected animals.201222554714
imported human rabies in a u.s. army soldier - new york, 2011.on august 19, 2011, a male u.s. army soldier with progressive right arm and shoulder pain, nausea, vomiting, ataxia, anxiety, and dysphagia was admitted to an emergency department (ed) in new york for suspected rabies. rabies virus antigens were detected in a nuchal skin biopsy, rabies virus antibodies in serum and cerebrospinal fluid (csf), and rabies viral rna in saliva and csf specimens by state and cdc rabies laboratories. an afghanistan canine rabies virus variant was identified. the patien ...201222552206
validation of the rapid fluorescent focus inhibition test for rabies virus-neutralizing antibodies in clinical samples.monoclonal antibodies are successful biologics in treating a variety of diseases, including the prevention or treatment of viral infections. cl184 is a 1:1 combination of two human monoclonal igg1 antibodies (cr57 and cr4098) against rabies virus, produced in the per.c6 human cell line. the two antibodies are developed as replacements of human rabies immune globulin (hrig) and equine rabies immune globulin (erig) in postexposure prophylaxis (pep). the rapid fluorescent focus inhibition test (rff ...201222547629
passive immunity in the prevention of rabies.prevention of clinical disease in those exposed to viral infection is an important goal of human medicine. using rabies virus infection as an example, we discuss the advances in passive immunoprophylaxis, most notably the shift from the recommended polyclonal human or equine immunoglobulins to monoclonal antibody therapies. the first rabies-specific monoclonal antibodies are undergoing clinical trials, so passive immunisation might finally become an accessible, affordable, and routinely used par ...201222541629
cat infected by a variant of bat rabies virus in a 29-year disease-free urban area of southern brazil.after 29 years, rabies was detected in a cat in curitiba, southern brazil.201222535002
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