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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
circulation of the rabies virus in non-hematophagous bats in the city of rio de janeiro, brazil, during 2001-2010.rabies is one of the most known lethal zoonosis, responsible for 55,000 human deaths per year. it is transmitted to humans mainly by the bite of domestic or wild animals infected with the virus. this paper shows the circulation of this virus in non-hematophagous bats in the city of rio de janeiro, brazil.201222534988
phylogenetic analysis of partial rna-polymerase blocks ii and iii of rabies virus isolated from the main rabies reservoirs in brazil.this study describes the results of the sequencing and analysis of segments of blocks ii and iii of the rna polymerase l gene of rabies virus isolates from different reservoir species of brazil. the phylogenetic relations of the virus were determined and a variety of species-specific nucleotides were found in the analyzed areas, but the majority of these mutations were found to be synonymous. however, an analysis of the putative amino acid sequences were shown to have some characteristic mutatio ...201222528640
evaluation of an improved rapid neutralizing antibody detection test (rapina) for qualitative and semiquantitative detection of rabies neutralizing antibody in humans and dogs.using the principle of immunochromatography, we previously developed a method called rapina (rapid neutralizing antibody detection test) that can measure the level of rabies virus -neutralizing antibody (vna) in serum samples [shiota s, mannen k, matsumoto t, yamada k, yasui t, takayama k, et al. development and evaluation of a rapid neutralizing antibody test for rabies. j virol methods 2009;161:58-62]. rapina is faster, simpler, and easier to perform compared with a virus-neutralizing test or ...201222516211
rabies risk assessment of exposures to a bat on a commercial airliner - united states, august 2011.on august 5, 2011, a bat flew through the cabin of a commercial airliner minutes after takeoff during an early morning flight from wisconsin to georgia, potentially exposing the passengers and flight crew to rabies virus. three days later, the wisconsin division of public health (wdph) requested assistance from cdc to conduct a rabies risk assessment for the passengers, flight crew, and ground crew members associated with the flight. no one was determined to have been exposed to rabies virus bas ...201222495227
extended incubation period of rabies virus in a captive big brown bat (eptesicus fuscus).rabies virus incubation in bats is typically less than 180 days, yet longer incubation periods have been described. we report a 267-day incubation in a big brown bat (eptesicus fuscus) exposed to rabies virus before entering our captive colony.201222493132
[vaccination against rabies: how and when?].each year, more than 55,000 people die from rabies. rabies virus (rabv) is transmitted via bites from infected animals. dogs represent the most important source of infections worldwide. in germany, the last case of terrestrial rabies was reported in 2006. therefore, the country has been considered rabies-free since september 2008 (as defined by world organization of animal health, oie). bat rabies, however, is still endemic and mostly occurs in northern germany. it is caused by the european bat ...201222492414
hierarchical connectivity and connection-specific dynamics in the corticospinal-corticostriatal microcircuit in mouse motor cortex.the generation of purposive movement by mammals involves coordinated activity in the corticospinal and corticostriatal systems, which are involved in different aspects of motor control. in the motor cortex, corticospinal and corticostriatal neurons are closely intermingled, raising the question of whether and how information flows intracortically within and across these two channels. to explore this, we developed an optogenetic technique based on retrograde transfection of neurons with deletion- ...201222492054
epidemiological and clinical features of human rabies cases in bali 2008-2010.previously thought to be rabies free, bali experienced an outbreak of animal and human rabies cases in november 2008. we describe the epidemiological and clinical data of human rabies cases occurring in the first two years of the outbreak.201222471410
assessment of inactivated human rabies vaccines: biochemical characterization and genetic identification of virus strains.the world health organization (who) recommends the periodic evaluation of the purity of the cell lines used in the production of rabies vaccines, as well as the antigenic identity of the virus strains. here, we analyzed seventeen marketed inactivated human rabies virus vaccines for viral and non-viral proteins by sds-page and coomassie/silver staining. mass spectrometric analysis of an abundant 60-70 kda signal indicated that in most vaccines serum albumin of human origin (hsa) was the major com ...201222469862
generation of a live rabies vaccine strain attenuated by multiple mutations and evaluation of its safety and efficacy.an amino acid substitution at position 333 in rabies virus g protein is known to determine the pathogenicity: strains with arg or lys at that position kill adult mice after intracerebral inoculation, whereas strains with other amino acids cause non-lethal infection. based on those findings, attenuated rabies virus strains have been established and used for oral vaccines mainly for wild animals. however, considering the possibility of back-mutation to the virulent phenotype, a strain that is atte ...201222464967
typing of the rabies virus in chile, 2002-2008.in chile, dog rabies has been controlled and insectivorous bats have been identified as the main rabies reservoir. this study aimed to determine the rabies virus (rabv) variants circulating in the country between 2002 and 2008. a total of 612 rabv isolates were tested using a panel with eight monoclonal antibodies against the viral nucleoprotein (n-mabs) for antigenic typing, and a product of 320-bp of the nucleoprotein gene was sequenced from 99 isolates. typing of the isolates revealed six dif ...201222458941
detection of antibodies against the rabies virus in korean raccoon dogs (nyctereutes procyonoides koreensis).rabies has been reported in dogs, cattle, and raccoon dogs in korea, especially in the provinces of gyeonggi and gangwon. the aim of this study was to investigate the seroprevalence of the rabies in wild korean raccoon dogs by using 50 blood samples collected in gyeonggi and gangwon provinces. antibodies against rabies were measured by using a fluorescent antibody virus neutralization test. of the 50 blood samples tested, 20 raccoon dogs (40%) tested positive. seropositive animals were distribut ...201222448528
new rabies virus found in tanzania. 201222447786
rvg peptide as transfection reagent for specific cdk4 gene silencing in vitro and in vivo.the rabies virus glycoprotein (rvg) peptide is known as a transfection reagent for systemic delivery of small interfering rna (sirna) into the brain. however, selective transfection of neuronal cells or specific brain regions remains a problem. in the present study, we show that the rvg peptide can efficiently be used as shuttle system to transfect neuronal cells with cdk4 sirna leading to selective knockdown of cdk4 expression in vitro and in vivo. after transfection, cdk4 expression was reduce ...201222443811
the 3' untranslated region of the rabies virus glycoprotein mrna specifically interacts with cellular pcbp2 protein and promotes transcript stability.viral polymerase entry and pausing at intergenic junctions is predicted to lead to a defined polarity in the levels of rhabdovirus gene expression. interestingly, we observed that the rabies virus glycoprotein mrna is differentially over-expressed based on this model relative to other transcripts during infection of 293t cells. during infection, the rabies virus glycoprotein mrna also selectively interacts with the cellular poly(rc)-binding protein 2 (pcbp2), a factor known to influence mrna sta ...201222438951
exposure to rabies virus in a population of free-ranging capuchin monkeys (cebus apella nigritus) in a fragmented, environmentally protected area in southeastern brazil.the aim of this study is to assess the frequency of rabies antibodies in free-ranging capuchin monkeys (cebus apella nigritus) in a fragmented, environmentally protected, rural area of southeastern brazil. thirty-six free-ranging monkeys were tested by the rapid fluorescent focus inhibition test for detection of antibodies against rabies virus. four individuals (11.11 %) had neutralizing antibody titers ≥ 0.25 iu/ml, demonstrating rabies virus exposure.201222430558
preparation and initial application of a monoclonal antibody specific for a newly discovered conserved linear epitope of rabies virus nucleoprotein.to prepare monoclonal antibodies against a newly discovered and conserved linear epitope of rabies virus nucleoprotein and to use them in a rabies diagnostic test.201222424633
the other rabies viruses: the emergence and importance of lyssaviruses from bats and other vertebrates.the recognition that viruses related to rabies virus cause rabies in humans has stimulated research into the relationships, geographic distribution and natural histories of these viruses. this paper reviews what is known of these fascinating viruses and the complexity of prevention and treatment of the disease they cause.201222386761
tacaribe virus causes fatal infection of an ostensible reservoir host, the jamaican fruit bat.tacaribe virus (tcrv) was first isolated from 11 artibeus species bats captured in trinidad in the 1950s during a rabies virus surveillance program. despite significant effort, no evidence of infection of other mammals, mostly rodents, was found, suggesting that no other vertebrates harbored tcrv. for this reason, it was hypothesized that tcrv was naturally hosted by artibeus bats. this is in stark contrast to other arenaviruses with known hosts, all of which are rodents. to examine this hypothe ...201222379103
first human rabies case in french guiana, 2008: epidemiological investigation and control.until 2008, human rabies had never been reported in french guiana. on 28 may 2008, the french national reference center for rabies (institut pasteur, paris) confirmed the rabies diagnosis, based on hemi-nested polymerase chain reaction on skin biopsy and saliva specimens from a guianan, who had never travelled overseas and died in cayenne after presenting clinically typical meningoencephalitis.201222363830
epidemiologic features of animal bite cases occurring in rabies-endemic areas of korea, 2005 to 2009.human rabies is a reemerging infectious disease in korea. there was no human rabies case for 14 years until the disease had reoccurred in 1999. to prevent occurrence of human rabies, surveillance for animal bite patients in rabies endemic areas in korea was conducted since 2005 as a part of a human rabies control program. the animal bite cases were analyzed to determine whether patients were treated according to the post-exposure prophylaxis (pep) guideline of the korea centers for disease contr ...201224159481
rabies virus distribution in tissues and molecular characterization of strains from naturally infected non-hematophagous bats.bats are main reservoirs for lyssavirus worldwide, which is an important public health issue because it constitutes one of the big challenges in rabies control. yet, little is known about how the virus is maintained among bats, and the epidemiological relationships remain poorly understood. the aim of the present study was to investigate the distribution of the rabies virus (rabv) in bat tissues and organs and to genetically characterize virus isolates from naturally infected non-hematophagous b ...201222349147
hsp70 protein positively regulates rabies virus infection.the hsp70 chaperone plays a central role in multiple processes within cells, including protein translation, folding, intracellular trafficking, and degradation. this protein is implicated in the replication of numerous viruses. we have shown that rabies virus infection induced the cellular expression of hsp70, which accumulated in negri body-like structures, where viral transcription and replication take place. in addition, hsp70 is present in both nucleocapsids purified from infected cells and ...201222345440
recovery of a patient from clinical rabies--california, 2011.in may 2011, a girl aged 8 years from a rural county in california was brought to a local emergency department (ed) with a 1-week history of progressive sore throat, difficulty swallowing, and weakness. after she developed flaccid paralysis and encephalitis, rabies was diagnosed based on 1) detection of rabies virus-specific antibodies in serum and cerebrospinal fluid (csf), 2) a compatible clinical syndrome in the patient, and 3) absence of a likely alternative diagnosis. the patient received a ...201222298301
withdrawn. tracking the footprints of the rabies virus: are we any closer to decoding this elusive virus? 201222272386
serial passage of a street rabies virus in mouse neuroblastoma cells resulted in attenuation: potential role of the additional n-glycosylation of a viral glycoprotein in the reduced pathogenicity of street rabies virus.street rabies viruses are field isolates known to be highly neurotropic. however, the viral elements related to their pathogenicity have yet to be identified at the nucleotide or amino acid level. here, through 30 passages in mouse neuroblastoma na cells, we have established an attenuated variant of street rabies virus strain 1088, originating from a rabid woodchuck followed by 2 passages in the brains of suckling mice. the variant, 1088-n30, was well adapted to na cells and highly attenuated in ...201222248643
comparing onrab® and raboral v-rg® oral rabies vaccine field performance in raccoons and striped skunks, new brunswick, canada, and maine, usa.control of rabies in mesocarnivore reservoirs through oral rabies vaccination (orv) requires an effective vaccine bait. oral rabies vaccine performance in the field may be affected by a variety of factors, including vaccine bait density and distribution pattern, habitat, target species population density, and the availability of competing foods. a field study in which these covariates were restricted as much as possible was conducted along the international border of the state of maine (me), usa ...201222247384
lack of robust lgn label following transneuronal rabies virus injections into macaque area v4.in primates, retinal inputs are relayed through the magno- and parvocells of the lateral geniculate nucleus (lgn) indirectly to extrastriate visual cortex. the most direct pathway identified to the extrastriate cortex is a disynaptic one that provides robust magno- and parvocellular inputs to the middle temporal area (mt). the inclusion of parvocells in this projection is somewhat surprising because of their importance for color and form vision, whereas mt is more strictly tuned to velocity. thi ...201222237967
targeted delivery of proteins into the central nervous system mediated by rabies virus glycoprotein-derived peptide.delivery of therapeutic proteins across the blood-brain barrier (bbb) is severely limited by their size and biochemical properties. here we showed that a 39-amino acid peptide derived from the rabies virus glycoprotein (rdp) was exploited as an efficient protein carrier for brain-targeting delivery.201222231987
[rhabdoviruses].the family rhabdoviridae has a non-segmented single stranded negative-sense rna and its genome ranges in size from approximately 11 kb to almost 16 kb. it is one of the most ecologically diverse families of rna viruses with members infecting a wide range of organisms. the five structural protein genes are arranged in the same linear order (3'-n-p-m-g-l-5') and may be interspersed with one more additional accessory gene. for many years, a full of knowledge of the rhabdoviridae has been establishe ...201224153229
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
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
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
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
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
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
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
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
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
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
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
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
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
[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
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
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
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
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
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
[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
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