Publications

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untangling neural networks with dual retrograde transsynaptic viral infection.using recombinant rabies virus (rv), we developed a dual transsynaptic retrograde tracing technique in the rat central nervous system. two strains of recombinant rv, injected into two separate loci of the brain, were taken up through axon terminals and carried retrogradely and transsynaptically from neuron to neuron. each viral strain expresses a unique marker in infected neurons. therefore, neurons that project transsynaptically to two brain loci can be detected by double-labeling. in this revi ...200920198151
evaluation of a rapid immunodiagnostic test kit for detection of african lyssaviruses from brain material.a rapid immunodiagnostic test kit was evaluated against a selection of isolates of lyssavirus genotypes occurring in africa. the test was carried out in parallel comparison with the fluorescent antibody test (fat) and isolates representing previously established phylogenetic groups from each genotype were included. the specificity of the rapid immunodiagnostic test compared favourably with the fat and was found to detect all representatives of genotypes 1, 2, 3 and 4 in brain samples of either f ...200920698445
interferon response and viral evasion by members of the family rhabdoviridae.like many animal viruses, those of the rhabdoviridae family, are able to antagonize the type i interferon response and cause disease in mammalian hosts. though these negative-stranded rna viruses are very simple and code for as few as five proteins, they have been seen to completely abrogate the type i interferon response early in infection. in this review, we will discuss the viral organization and type i interferon evasion of rhabdoviruses, focusing on vesicular stomatitis virus (vsv) and rabi ...200921994572
use of latex agglutination test to determine rabies antibodies in production of rabies antisera in horses.a therapeutic anti-rabies immunoglobulin for human use has been produced mainly in horses. the presently available seroneutralization test, the rapid fluorescent focus inhibition test (rffit), is laborious and rather difficult to carry out in horse farms. this study was undertaken to develop a simple latex agglutination test (lat) for determining rabies antibodies in horse sera. lat was validated by testing a total of 468 horse serum samples characterized by rffit. of these, 253 of 260 samples w ...201021329315
resistance to rabies virus infection conferred by the pmliv isoform.various reports implicate pml and pml nuclear bodies (nbs) in an intrinsic antiviral response targeting diverse cytoplasmic replicating rna viruses. pml conjugation to the small ubiquitin-like modifier (sumo) is required for its localization within nbs. pml displays antiviral effects in vivo, as pml deficiency renders mice more susceptible to infection with the rhabdovirus vesicular stomatitis virus (vsv). cells derived from these mice are also more sensitive to infection with rabies virus, anot ...201020702643
characterization of major histocompatibility complex (mhc) drb exon 2 and dra exon 3 fragments in a primary terrestrial rabies vector (procyon lotor).the major histocompatibility complex (mhc) presents a unique system to explore links between genetic diversity and pathogens, as diversity within mhc is maintained in part by pathogen driven selection. while the majority of wildlife mhc studies have investigated species that are of conservation concern, here we characterize mhc variation in a common and broadly distributed species, the north american raccoon (procyon lotor). raccoons host an array of broadly distributed wildlife diseases (e.g., ...201020706587
intracerebral vaccination suppresses the spread of rabies virus in the mouse brain.to investigate the efficacy of intracerebral (ic) immunization in preventing viral spread in the brain, we immunized mice with inactivated rabies virus via the subcutaneous (sc) or ic route, followed by administration of a lethal dose of rabies virus (challenge virus standard strain), directly into the brains of immunized mice. progressive paralytic neurological signs were observed in control and 75% of sc immunized mice, whereas only 20% of ic immunized mice exhibited symptoms. neutralizing ant ...201020713172
validation of a less invasive blood sampling technique in rabies serology using reduviid bugs (triatominae, hemiptera).during serologic rabies surveys, bleeding is often difficult or almost impossible in small or endangered mammals such as bats. therefore, the usefulness of an alternative, less invasive technique--that is, the use of blood-sucking reduviid bugs (dipetalogaster maximus and rhodnius prolixus)--was investigated. bugs were used in combination with a conventional method (retro-orbitale bleeding) to obtain blood samples from the same individual nmri-mice (mus musculus) vaccinated against rabies. rabie ...201020722255
response to vaccination with a commercial inactivated rabies vaccine in a captive colony of brazilian free-tailed bats (tadarida brasiliensis).a captive colony of brazilian free-tailed bats (tadarida brasiliensis) was vaccinated with a commercial monovalent inactivated rabies virus (rabv) vaccine (rabvac 1). baseline rabies virus neutralizing antibodies (vna) and the response to vaccination were measured in 50 bats. rabies vna was detected in the plasma of 64% (27/42) of bats that had been vaccinated 1 yr prior, but only 19% (8/42) had levels considered adequate. rabies vna was detected in the plasma of 63% (5/8) of bats with no record ...201020722268
[optimization of method of titration rabies virus with fluorescence focus units assay].a new fluorescence focus units (ffu) developed for rabies virus titration replace current reference method (ld50) so as to reduce the cost.201020726271
dendritic cells infected by recombinant rabies virus vaccine vector expressing hiv-1 gag are immunogenic even in the presence of vector-specific immunity.dendritic cells (dc) are the most potent antigen presenting cells whose ability to interact with t cells, b cells and nk cells has led to their extensive use in vaccine design. here, we designed a dc-based hiv-1 vaccine using an attenuated rabies virus vector expressing hiv-1 gag (ridc-gag). to test this, balb/c mice were immunized with ridc-gag, and the primary, secondary as well as humoral immune responses were monitored. our results indicate that ridc-gag stimulated hiv-1 gag-specific immune ...201020728525
[the primary closure approach of dog bite injuries of the nose].biting of humans by domestic animals, especially by dogs, is common injury which causes suffering and pain, might be a cause of disability or even death. it is associated with high risk of bacterial infection of the wounds or even transfection of rabies virus. bites are usually to the upper and lower limbs, while the face is third in a raw localization of bites. within the face, the nose and lips are injured the most often. the goal of this paper is presentation selected methods and obtained res ...201020731205
improved safety for molecular diagnosis of classical rabies viruses by use of a taqman real-time reverse transcription-pcr "double check" strategy.to improve the diagnosis of classical rabies virus with molecular methods, a validated, ready-to-use, real-time reverse transcription-pcr (rt-pcr) assay was developed. in a first step, primers and 6-carboxyfluorescien-labeled taqman probes specific for rabies virus were selected from the consensus sequence of the nucleoprotein gene of 203 different rabies virus sequences derived from genbank. the selected primer-probe combination was highly specific and sensitive. during validation using a sampl ...201020739489
targeting single neuronal networks for gene expression and cell labeling in vivo.to understand fine-scale structure and function of single mammalian neuronal networks, we developed and validated a strategy to genetically target and trace monosynaptic inputs to a single neuron in vitro and in vivo. the strategy independently targets a neuron and its presynaptic network for specific gene expression and fine-scale labeling, using single-cell electroporation of dna to target infection and monosynaptic retrograde spread of a genetically modifiable rabies virus. the technique is h ...201020797534
rabies and african bat lyssavirus encephalitis and its prevention.unlike any other human infection, encephalitis caused by dog rabies virus is always fatal. rabies and other lyssaviruses have been found in unexpected places, and human disease, especially paralytic rabies, has gone unrecognised. evidence is emerging that rabies-related bat lyssaviruses are enzootic across europe, africa, asia and australia, but none has been detected in the americas. the epidemiology and origins of african lyssaviruses are discussed. ideal rabies prophylaxis (pre-exposure immun ...201020801003
selective viral vector transduction of erbb4 expressing cortical interneurons in vivo with a viral receptor-ligand bridge protein.both treatment of disease and basic studies of complex tissues can benefit from directing viral vector infection to specific cell types. we have used a unique cell targeting method to direct viral vector transduction to cerebral cortical neurons expressing the neuregulin (nrg) receptor erbb4; both nrg and erbb4 have been implicated in schizophrenia, and erbb4 expression in cerebral cortex is known to be restricted to inhibitory neurons. we find that a bridge protein composed of the avian viral r ...201020823240
[the development of neutralizing human antibodies against rabies virus].a combinatorial human fab library to the rabies virus was constructed using antibody genes derived from the blood of vaccinated donors. the library were panned and selected on purified rabies virus particles of ag or ctn strain with phage display. eleven unique human fab antibodies specific for the rabies virus glycoprotein were obtained by elisa, ifa and dna sequences analysis of these antibodies. among these fab antibodies, five human fab antibodies were converted to full-length human igg anti ...201020836379
a rapid immunochromatographic test strip for detecting rabies virus antibody.an immunochromatographic test strip (icts) for detecting antibodies to rabies virus was developed, using colloidal gold particles labeled with rabies virus glycoprotein as the tracer. the assay was evaluated using sera from dogs immunized with various commercial rabies vaccines, or from dogs in the clinics and sera from dogs immunized with vaccines against pathogens other than rabies virus, and negative sera from a wide variety of animal sources, including dogs, mice, and cats which had never be ...201020837065
rabies surveillance in the united states during 2009.during 2009, 49 states and puerto rico reported 6,690 rabid animals and 4 human rabies cases to the cdc, representing a 2.2% decrease from the 6,841 rabid animals and 2 human cases reported in 2008. approximately 92% of reported rabid animals were wildlife. relative contributions by the major animal groups were as follows: 2,327 (34.8%) raccoons, 1,625 (24.3%) bats, 1,603 (24.0%) skunks, 504 (75%) foxes, 300 (4.5%) cats, 81 (1.2%) dogs, and 74 (1.1%) cattle. compared with 2008, numbers of rabid ...201020839985
molecular epidemiology of rabies virus in mongolia, 2005-2008.the objective of this study was to determine the genetic diversity of rabies virus (rabv) in mongolia based on the nucleotide sequences of viral n gene. a total of 24 rabies-positive samples from seven different domestic and wild animal species collected in western and central mongolia between 2005 and 2008 were examined for their n gene sequences. the results showed that the endemic mongolian rabvs could be divided into two different groups closely related to the steppe-type and arctic-like vir ...201020859006
immunogenicity, safety and tolerance of a purified duck embryo vaccine (pdev, vaxirab) for rabies post-exposure prophylaxis: results of a multicentric study in india.rabies continues to be a major public health problem in india. nearly 17 million people are getting exposed to this disease every year. therefore the need for effective post-exposure prophylaxis with safe and potent modern rabies vaccines continues to exist. purified duck embryo vaccine (pdev) was introduced in this country to meet the ever increasing need for modern rabies vaccines. in this study we have assessed the safety, imunogenicity and tolerance of an indigenously manufactured pdev in pe ...201020861692
amino acids at positions 273 and 394 in rabies virus nucleoprotein are important for both evasion of host rig-i-mediated antiviral response and pathogenicity.we previously reported that nucleoprotein (n) is related to the different pathogenicities of the virulent rabies virus strain nishigahara (ni) and avirulent strain ni-ce and also that ni n, but not ni-ce n, functions to evade retinoic acid-inducible gene i (rig-i)-mediated innate immunity. there are three amino acid differences between ni and ni-ce n (at positions 273, 394 and 395), indicating that one of these mutations or a combination of mutations is important for the pathogenicity and evasio ...201020875468
human rabies---virginia, 2009.on october 28, 2009, cdc notified the virginia department of health (vdh) of suspected rabies in a virginia man aged 42 years. earlier that day, an infectious disease physician in virginia had contacted cdc requesting confirmatory diagnostic testing and reported initiating treatment with the milwaukee protocol after consultation with staff at the medical college of wisconsin. this report summarizes the patient's exposure history, clinical course, and treatment, and describes efforts to identify ...201020881935
[production and evaluation of an antiserum for immunohistochemical detection of rabies virus in aldehyde fixed brain tissues].the standard procedure for rabies diagnosis requires fresh samples of infected brain to be analyzed by two techniques, direct immunofluorescence and inoculation in mice. rabies-infected, aldehyde-fixed brain tissues can be examined by immunohistochemistry, but the required commercial antibodies are scarce and expensive.201020890559
experimental rabies vaccines for humans.rabies remains a global public health threat that kills more than 55,000 people per year. rabies disproportionately affects children and, therefore, is ranked the seventh most important infectious disease due to years lost. prevention of human rabies is accomplished by controlling rabies in domestic and wild animals, including the use of vaccination programs. the usefulness of human rabies vaccines is hampered by high cost, complicated vaccination regimens and lack of compliance, especially in a ...201020923268
mhc class ii drb diversity in raccoons (procyon lotor) reveals associations with raccoon rabies virus (lyssavirus).in north america, the raccoon rabies virus (rrv) is an endemic wildlife disease which causes acute encephalopathies and is a strong selective force on raccoons (procyon lotor), with estimates of ∼85% of the population succumbing to the disease when epizootic. rrv is regarded as a lethal disease if untreated; therefore, no evolutionary response would be expected of raccoon populations. however, variable immune responses to rrv have been observed in raccoons indicating a potential for evolutionary ...201020924575
molecular studies of influenza b virus in the reverse genetics era.recovery of an infectious virus of defined genetic structure entirely from cdna and the deduction of information about the virus resulting from phenotypic characterization of the mutant is the process of reverse genetics. this approach has been possible for a number of negative-strand rna viruses since the recovery of rabies virus in 1994. however, the recovery of recombinant orthomyxoviruses posed a greater challenge due to the segmented nature of the genome. it was not until 1999 that such a s ...201020926635
evolutionary history of dog rabies in brazil.although dogs are considered to be the principal transmitter of rabies in brazil, dog rabies had never been recorded in south america before european colonization. in order to investigate the evolutionary history of dog rabies virus (rabv) in brazil, we performed a phylogenetic analysis of carnivore rabv isolates from around the world and estimated the divergence times for dog rabv in brazil. our estimate for the time of introduction of dog rabv into brazil was the late-19th to early-20th centur ...201020926638
targeted delivery of large fusion protein into hippocampal neurons by systemic administration.targeted delivery of proteins into the hippocampus has not yet been achieved. here, we show that systemic administration of the β-galactosidase, fused to a 43-amino-acid peptide derived from rabies virus glycoprotein (rvg), results in targeted delivery of the fusion protein into the hippocampal neurons. this approach may enable the development of protein therapy for neurodegenerative diseases, such as alzheimer's disease. this result may open new possibilities in using neurotropic virus glycopro ...201020932231
utility of human embryonic kidney cell line hek-293 for rapid isolation of fixed and street rabies viruses: comparison with neuro-2a and bhk-21 cell lines.a confirmatory rabies diagnosis can be achieved by rapid virus isolation in cell culture using brain tissue from the suspect animal. several cell lines have been used for this purpose and the murine neuroblastoma cell line neuro-2a has been found to be the most sensitive. the human embryonic kidney cell line hek-293 is known to express several neuronal proteins and is believed to be of neuronal origin. we hypothesized that this cell line could be susceptible to rabies virus, which is highly neur ...201020947403
[the use of passive rabies immunotherapy: from the past to the future].rabies is a fatal disease transmitted by infected animals by bite, scratch, licking on broken skin or contamination of mucosis by saliva. the regimen of post-exposure prophylaxis for people not previously vaccinated, that is currently recommended by who, consists of a combination of wound cleaning, active immunization and passive immunization when the exposure is of category 3. most of the products available on the market, in particular human rabies immunoglobulins, highly purified equine rabies ...201020950578
virus neutralising activity of african fruit bat (eidolon helvum) sera against emerging lyssaviruses.it is likely that phylogroup 2 lyssaviruses circulate within bat reservoirs. we adapted a pseudotype (pt) neutralisation assay (pna) to a multiplex format enabling serosurveillance for lagos bat virus (lbv), mokola virus (mokv) and west caucasian bat virus (wcbv) in a potential reservoir, the african straw-coloured fruit bat, eidolon helvum. highly correlated titres were observed between single and multiplex pnas using ptlbv and ptmokv (r=0.97, p<0.0001), validating its use for bat serosurveilla ...201020951400
immunohistochemical study of rabies virus within the central nervous system of domestic and wildlife species.immunohistochemistry using a commercial polyclonal antibody for lyssavirus was applied to 39 archival cases of rabies. paraffin blocks from 13 different species were available, including 3 dogs, 4 cats, 1 pig, 6 cattle, 4 horses, 1 llama, 7 skunks (mephitis mephitis), 7 raccoons (procyon lotor), 1 bat (myotis species), 1 white-tailed deer (odocoileus virginianus), 1 bobcat (lynx rufus), 2 gray foxes (urocyon cinereoargenteus), and 1 red fox (vulpes vulpes). all cases had previously been diagnose ...201020484176
a new outbreak of rabies in rare ethiopian wolves (canis simensis).between october 2008 and may 2009, five brain samples from the carcasses of the rare ethiopian wolf (canis simenensis) were submitted for rabies virus testing. rabies virus was detected in all five samples, and this confirmed that a further outbreak of rabies had occurred within the wolf population in the bale mountains of ethiopia. sequence comparison of a partial fragment of the nucleoprotein-coding gene demonstrated that all viruses showed 100% sequence identity, suggesting a single introduct ...201020490607
analysis of chinese rabies virus isolates from 2003-2007 based on p and m protein genes.phylogenetic analysis of nucleotide sequences or deduced amino acid sequences of phosphoprotein (p protein), matrix (m) protein, and glycoprotein (g protein) genes of 18 chinese isolates of rabies virus (rabv) from 2003-2007 showed that these isolates formed a separate monophyletic lineage consisting of sub-lineages a and b. compared with laboratory-fixed strains, recent chinese isolates of sub-lineage b contained val or ala instead of met69 in p protein, which is involved in generating truncate ...201020545436
contrasting landscape epidemiology of two sympatric rabies virus strains.viral strain evolution and disease emergence are influenced by anthropogenic change to the environment. we investigated viral characteristics, host ecology, and landscape features in the rabies-striped skunk disease system of the central great plains to determine how these factors interact to influence disease emergence. we amplified portions of the n and g genes of rabies viral rna from 269 samples extracted from striped skunk brains throughout the distribution of two different rabies strains f ...201020546130
loop 2 of ophiophagus hannah toxin b binds with neuronal nicotinic acetylcholine receptors and enhances intracranial drug delivery.three-finger snake neurotoxins have been widely investigated for their high binding affinities with nicotinic acetylcholine receptors (nachrs), which are widely expressed in the central nervous system including the blood-brain barrier and thus mediate intracranial drug delivery. the loop 2 segments of three-finger snake neurotoxins are considered as the binding domain with nachrs, and thus, they may have the potential to enhance drug or drug delivery system intracranial transport. in the present ...201020964364
detection of rabies virus antibodies in brazilian free-ranging wild carnivores.rabies virus is a pathogen of major concern in free-ranging wild carnivores in several regions of the world, but little is known about its circulation in brazilian wild carnivores. sera from 211 free-ranging wild carnivores, captured from 2000 to 2006 in four locations of two brazilian biomes (pantanal and cerrado), were tested for rabies antibodies. twenty-six individuals (12.3%) had neutralizing antibody titers ≥0.10 iu/ml. the four sampled locations had antibody-positive animals, suggesting t ...201020966286
a comparative study of rabies virus isolates from hematophagous bats in brazil.the brazilian chiropteran fauna consists of 167 species; of which, three are hematophagous: the common vampire bat (desmodus rotundus), the white-winged vampire bat (diaemus youngi), and the hairy-legged vampire bat (diphylla ecaudata). the aim of this study was to describe the isolation of rabies virus from common and hairy-legged vampire bats and to report the first comparative antigenic and genetic studies of isolates from these bats. antigenic and genetic typing of both isolates identified t ...201020966291
molecular characterization of rabies virus isolated from dogs in tunisia: evidence of two phylogenetic variants.in an attempt to explain temporal and geographical rabies incidence fluctuations in tunisia, a molecular epidemiological study of rabies virus (rv) was carried out. a panel of rv isolates from dogs, collected between 1992 and 2003, from different regions in tunisia have been analysed by direct sequencing of pcr-amplified products coding for the nucleoprotein gene. new sequences have been compared to prototype sequences of lyssavirus species and nine lineages of species 1. all tunisian isolates b ...201020970468
[a human rabies case with antemortem diagnosis].rabies, which is an acute, progressive, fatal zoonotic infectious disease, is almost always caused by the bite of rabid animals containing rabies virus in their saliva. since there is no established specific therapy for rabies, preventive and prophylactic measures are of critical importance. in this report a case of human rabies diagnosed antemortem, was presented. a 29 year old man was admitted to harran university hospital (in sanliurfa province, located at southeastern anatolia) emergency ser ...201020549967
comparative analysis of rabies virus reverse transcription-pcr and virus isolation using samples from a patient infected with rabies virus.definite and rapid diagnosis of rabies is required for individual case management as well as for public health. for the first time, a direct comparison of virus isolation with quantitative real-time reverse transcription (rt)-pcr on human rabies samples was conducted. rt-pcr was found to be more sensitive than virus isolation.201020554825
reassessing the risk from rabies: a continuing threat to the uk?the threat of re-introduction of rabies virus into the united kingdom exists on several levels. firstly, importation of live animals into the uk continues to challenge the regulations in place to ensure that the virus does not enter the country. secondly, the indigenous bat population is known to carry a virus genetically related to rabies virus, the european bat lyssavirus (eblv). molecular characterization of this virus has further characterized it as being eblv type 2, genetically distinct fr ...201020558215
[analysis of full-length gene sequence of a rabies vaccine strain ctn-1 for human use in china].ctn-1 is one of the rabies vaccine strains for human use in china, but there has been no report on the full-length gene sequence of ctn-1. in this study, the full-length gene of ctn-1 was amplified by rt-pcr, each pcr product was cloned into t vector and then sequenced, assemblied and compared with other vaccine strains as well as the wild chinese rabies isolates. the phylogenetic tree of g gene was constructed and the genetic homology was analyzed. the results revealed that ctn-1 was 11 925nt ( ...201020572340
recombinant diabody-based immunocapture enzyme-linked immunosorbent assay for quantification of rabies virus glycoprotein.the potency of rabies vaccines, determined using the nih mouse protection test, can be directly correlated to the amount of rabies virus glycoprotein (rv gp) present in the vaccine. in an effort to develop a simple and sensitive enzyme-linked immunosorbent assay (elisa) using recombinant diabody for quantification of rv gp, the variable heavy (v(h)) and light chain (v(l)) domains of an rv gp-specific human monoclonal antibody (mab) secreted by a human x mouse heterohybridoma (human mab r16e5) wa ...201020573881
subcapsular sinus macrophages prevent cns invasion on peripheral infection with a neurotropic virus.lymph nodes (lns) capture microorganisms that breach the body's external barriers and enter draining lymphatics, limiting the systemic spread of pathogens. recent work has shown that cd11b(+)cd169(+) macrophages, which populate the subcapsular sinus (scs) of lns, are critical for the clearance of viruses from the lymph and for initiating antiviral humoral immune responses. here we show, using vesicular stomatitis virus (vsv), a relative of rabies virus transmitted by insect bites, that scs macro ...201020577213
rig-i mediates nonsegmented negative-sense rna virus-induced inflammatory immune responses of primary human astrocytes.while astrocytes produce key inflammatory mediators following exposure to neurotropic nonsegmented negative-sense rna viruses such as rabies virus and measles virus, the mechanisms by which resident central nervous system (cns) cells perceive such viral challenges have not been defined. recently, several cytosolic dexd/h box rna helicases including retinoic acid-inducible gene i (rig-i) have been described that function as intracellular sensors of replicative rna viruses. here, we demonstrate th ...201020578054
expression of mip-1alpha (ccl3) by a recombinant rabies virus enhances its immunogenicity by inducing innate immunity and recruiting dendritic cells and b cells.previously, we showed that overexpression of mip-1alpha in mouse brain further decreased rabies virus (rabv) pathogenicity (l. zhao, h. toriumi, y. kuang, h. chen, and z. f. fu, j. virol., 83:11808-11818, 2009). in the present study, the immunogenicity of recombinant rabv expressing mip-1alpha (rhep-mip1alpha) was determined. it was found that intramuscular immunization of balb/c mice with rhep-mip1alpha resulted in a higher level of expression of mip-1alpha at the site of inoculation, increased ...201020592092
characterization of a panel of anti-phosphoprotein monoclonal antibodies generated against the raccoon strain of rabies virus.the generation of a new panel of 32 monoclonal antibodies (mabs) reactive with the p protein of the raccoon strain of rabies virus is described. through a series of analyses employing competitive elisa and immunoblotting, these mabs were classified into eight groups, each defining an antigenic site, thereby increasing the number of sites now recognized along the length of the p protein. studies on mab reactivity with a collection of diverse lyssaviruses identified sites that were highly conserve ...201020600390
safety and efficacy of novel dermal and epidermal microneedle delivery systems for rabies vaccination in healthy adults.in the present pilot study, intradermal id delivery systems with a bd microneedle from 1 to 3mm in length, and epidermal delivery (bd skin abrader) through abraded skin surface relative to standard intramuscular injection were evaluated. circulating neutralizing antibodies were measured against the rabies virus after the vero cells rabies vaccine was administered at d0, d7, d21 and d49. this clinical evaluation in 66 healthy volunteers shows that id delivery using bd microneedle technology of 1/ ...201020600481
fine mapping and interaction analysis of a linear rabies virus neutralizing epitope.a novel human antibody ar16, targeting the g5 linear epitope of rabies virus glycoprotein (rvg) was shown to have promising antivirus potency. using ar16, the minimal binding region within g5 was identified as hdfr (residues 261-264), with key residues hdf (residues 261-263) identified by alanine replacement scanning. the key hdf was highly conserved within phylogroup i lyssaviruses but not those in phylogroup ii. using computer-aided docking and interaction models, not only the key residues (as ...201020601078
rabies virus in insectivorous bats: implications of the diversity of the nucleoprotein and glycoprotein genes for molecular epidemiology.insectivorous bats are the main reservoirs of rabies virus (rabv) in various regions of the world. the aims of this study were to (a) establish genealogies for rabv strains from different species of brazilian insectivorous bats based on the nucleoprotein (n) and glycoprotein (g) genes, (b) investigate specific rabv lineages associated with certain genera of bats and (c) identify molecular markers that can distinguish between these lineages. the genealogic analysis of n and g from 57 rabv strains ...201020609456
generation of recombinant european bat lyssavirus type 1 and inter-genotypic compatibility of lyssavirus genotype 1 and 5 antigenome promoters.bat lyssaviruses (fam. rhabdoviridae) represent a source for the infection of terrestial mammals and the development of rabies disease. molecular differences in the replication of bat and non-bat lyssaviruses and their contribution to pathogenicity, however, are unknown. one reason for this is the lack of reverse genetics systems for bat-restricted lyssaviruses. to investigate bat lyssavirus replication and host adaptation, we developed a reverse genetics system for european bat lyssavirus type ...201020614145
two overlapping domains of a lyssavirus matrix protein that acts on different cell death pathways.the lyssavirus matrix (m) protein induces apoptosis. the regions of the m protein that are essential for triggering cell death pathways are not yet clearly defined. we therefore compared the m proteins from two viruses that have contrasting characteristics in terms of cellular apoptosis: a genotype 3 lyssavirus, mokola virus (mok), and a genotype 1 rabies virus isolated from a dog from thailand (tha). we identified a 20-amino-acid fragment (corresponding to positions 67 to 86) that retained the ...201020631119
seroconversion following incomplete human rabies postexposure prophylaxis.in august 2008, cdc and the puerto rico department of health conducted a serosurvey of patients who had discontinued rabies postexposure prophylaxis (pep) prior to completing a schedule of five vaccine doses. the objective was to determine whether further vaccination of these patients was needed based on serum rabies neutralizing antibody levels. eighteen patients consented to serology using the rapid fluorescent focus inhibition test. the world health organization's cutoff value of 0.5 iu/ml wa ...201020637309
human rabies transmitted by vampire bats: antigenic and genetic characterization of rabies virus isolates from the amazon region (brazil and ecuador).since 2004, the main transmitter of human rabies in latin america has been the vampire bat (desmodus rotundus). based on the nucleoprotein of the rabies virus (rv), we analyzed antigenic and genetic profiles of isolates from 29 samples taken from humans living in different areas of the amazon region. two isolates were from ecuador and 27 from the northern and northeastern regions of brazil, which were obtained during outbreaks in various municipalities in the states of pará and maranhão in the y ...201020637811
use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies-recommendations of the advisory committee on immunization practice. 201020648715
impact of emergency oral rabies vaccination of foxes in northeastern italy, 28 december 2009-20 january 2010: preliminary evaluation.fox rabies re-emerged in northeastern italy in 2008, in an area bordering slovenia. in 2009, the infection spread westward to veneto region and in 2010 to the provinces of trento and bolzano. aerial emergency oral fox vaccination was implemented in the winter 2009-10. since this vaccination was performed at altitudes below the freezing level, a statistical analysis was conducted to evaluate its impact. of the foxes sampled following the vaccination campaign, 77% showed a rabies antibody titre of ...201020650054
transmission dynamics of rabies in china over the last 40 years: 1969-2009.rabies is a serious reemerging zoonosis in china. the molecular evolution and transmission patterns of rabies virus inferred from historical data can provide guidelines for better disease control and prevention in the future.201020650678
rabies virus infection induces type i interferon production in an ips-1 dependent manner while dendritic cell activation relies on ifnar signaling.as with many viruses, rabies virus (rabv) infection induces type i interferon (ifn) production within the infected host cells. however, rabv has evolved mechanisms by which to inhibit ifn production in order to sustain infection. here we show that rabv infection of dendritic cells (dc) induces potent type i ifn production and dc activation. although dcs are infected by rabv, the viral replication is highly suppressed in dcs, rendering the infection non-productive. we exploited this finding in bo ...201020661430
induction of neutralizing antibody responses to anthrax protective antigen by using influenza virus vectors: implications for disparate immune system priming pathways.viral vectors based on influenza virus, rabies virus (rv), and vaccinia virus (vv) were used to express large polypeptide segments derived from the bacillus anthracis protective antigen (pa). for the infectious influenza virus vector and recombinant vv constructs, the receptor binding domain (rbd or domain 4) or the lethal and edema factor binding domain (lef or domain 1') were engineered into functional chimeric hemagglutinin (ha) glycoproteins. in the case of the rv vector, the viral glycoprot ...201020504926
[an epidemiological investigation of the rabies between 1999 - 2008 in yancheng city, jiangsu province.].to better understand the epidemiology of rabies during the past ten years in yancheng city, jiangsu province.201020510058
immunovirological correlates in human rabies treated with therapeutic coma.a 37-year-old woman was admitted to hospital and over the next 5 days developed a progressive encephalitis. nuchal skin biopsy, analyzed using a rabies taqman(c) pcr, demonstrated rabies virus rna. she had a history in keeping with exposure to rabies whilst in south africa, but had not received pre- or post-exposure prophylaxis. she was treated with a therapeutic coma according to the "milwaukee protocol," which failed to prevent the death of the patient. rabies virus was isolated from csf and s ...201020513093
[the establishment of a rapid fluorescent focus inhibition test for testing rabies virus neutralizing antibody.].to establish a rapid fluorescent inhibition test (rffit) for testing rabies virus neutralizing antibody and the titer of rabies virus neutralizing antibody. cvs-11 was used as the standard challenge virus, and three generations prepared for the establishment of the virus library.201020513292
host immunity to repeated rabies virus infection in big brown bats.bats are natural reservoirs for the majority of lyssaviruses globally, and are unique among mammals in having exceptional sociality and longevity. given these facets, and the recognized status of bats as reservoirs for rabies viruses (rabvs) in the americas, individual bats may experience repeated exposure to rabv during their lifetime. nevertheless, little information exists with regard to within-host infection dynamics and the role of immunological memory that may result from abortive rabv inf ...201020519458
characterization of conformation-specific monoclonal antibodies against rabies virus nucleoprotein.three anti-rabies virus (rabv) nucleoprotein (n) monoclonal antibodies (mab) were characterized by immunofluorescence assays, western blotting, and immunohistochemistry. one of these mabs recognized the antigen by all of the assays, while the other two recognized n only in the native form in the immunofluorescence assay. these data, together with epitope mapping studies, suggest that two anti-n mabs recognize conformational epitopes located within the n-terminal region of the rabv n protein. the ...201020521069
why does the prognosis remain so poor in human rabies? 201020521888
assessing the relationship between antigenicity and immunogenicity of human rabies vaccines when administered by intradermal route: results of a metaanalysis.the metadata of 10 published studies and 3 vaccine trial reports comprising of 19 vaccine cohorts from four countries conducted over a period of 23 years (1986 - 2009) was used for metaanalysis. the vaccines studied were purified chick embryo cell vaccine (rabipur, india & germany), purified vero cell rabies vaccine (verorab, france; indirab, india) & human diploid cell vaccine (mirv, france).the potency of these vaccines varied from 0.55 iu to 2.32 iu per intradermal dose of 0.1 ml per site. th ...201020523131
molecular basis of neurovirulence of flury rabies virus vaccine strains: importance of the polymerase and the glycoprotein r333q mutation.the molecular mechanisms associated with rabies virus (rv) virulence are not fully understood. in this study, the rv flury low-egg-passage (lep) and high-egg-passage (hep) strains were used as models to explore the attenuation mechanism of rv. the results of our studies confirmed that the r333q mutation in the glycoprotein (g(r333q)) is crucial for the attenuation of flury rv in mice. the r333q mutation is stably maintained in the hep genome background but not in the lep genome background during ...201020538851
bat rabies in massachusetts, usa, 1985-2009.to investigate rabies in massachusetts, we analyzed bat rabies test results before and after introduction of raccoon variant rabies and after release of revised 1999 us advisory committee on immunization practices recommendations for rabies postexposure prophylaxis. bat submissions were associated with level of rabies awareness and specific postexposure recommendations.201020678326
imported human rabies, the philippines and finland, 2007. 201020678336
nk cells as effectors of acquired immune responses: effector cd4+ t cell-dependent activation of nk cells following vaccination.we characterized vaccine-induced cellular responses to rabies virus in naive adult volunteers. contrary to current paradigms, we observed potent and prolonged in vitro nk cell cytokine production and degranulation responses after restimulation of pbmcs with inactivated rabies virus in vaccinated, but not in unvaccinated, individuals. this "recall" nk cell response was absolutely dependent on ag-specific il-2 from cd45ro(+) cd4(+) t cells as well as il-12 and il-18 from accessory cells. important ...201020679529
coexpression of double or triple copies of the rabies virus glycoprotein gene using a 'self-cleaving' 2a peptide-based replication-defective human adenovirus serotype 5 vector.rabies virus glycoprotein (rvg) is a major structural protein and antigen of rabies virus that induces a highly immunogenic response. in the present study, we have used 2a self-cleaving sequence of the foot-and-mouth disease virus (fmdv) to express double or triple copies of the rvg from a single open reading frame derived from human adenovirus 5 (adhu5). the recombinant adenoviruses produce similar virus titers, indicating that the insertion of double or triple copies of the rvg gene linked wit ...201020682459
fatal canine distemper infection in a pack of african wild dogs in the serengeti ecosystem, tanzania.in 2007, disease related mortality occurred in one african wild dog (lycaon pictus) pack close to the north-eastern boundary of the serengeti national park, tanzania. histopathological examination of tissues from six animals revealed that the main pathologic changes comprised interstitial pneumonia and suppurative to necrotizing bronchopneumonia. respiratory epithelial cells contained numerous eosinophilic intracytoplasmic inclusion bodies and multiple syncytial cells were found throughout the p ...201020684868
adenovirus-based vaccines: comparison of vectors from three species of adenoviridae.in order to better understand the broad applicability of adenovirus (ad) as a vector for human vaccine studies, we compared four adenovirus (ad) vectors from families c (ad human serotype 5 [hadv-5; here referred to as adhu5]), d (hadv-26; here referred to as adhu26), and e (simian serotypes sadv-23 and sadv-24; here referred to as chimpanzee serotypes 6 and 7 [adc6 and adc7, respectively]) of the adenoviridae. seroprevalence rates and titers of neutralizing antibodies to the two human-origin ad ...201020686035
field evaluation of an inactivated vaccine to control raccoon rabies in ontario, canada.since raccoon rabies first appeared in ontario in 1999, >90,000 raccoons (procyon lotor) have received imrab3 inactivated rabies vaccine via intramuscular (im) injection and were released at the point of capture as part of a multiyear rabies control program, trap-vaccinate-release (tvr). of the 132 confirmed cases infected with raccoon-variant rabies virus in ontario between 1999 and 2005, two were from that vaccinated group, as indicated by the presence of identifying ear tags. during ongoing r ...201020688688
host phylogeny constrains cross-species emergence and establishment of rabies virus in bats.for rna viruses, rapid viral evolution and the biological similarity of closely related host species have been proposed as key determinants of the occurrence and long-term outcome of cross-species transmission. using a data set of hundreds of rabies viruses sampled from 23 north american bat species, we present a general framework to quantify per capita rates of cross-species transmission and reconstruct historical patterns of viral establishment in new host species using molecular sequence data ...201020689015
ferret badger rabies origin and its revisited importance as potential source of rabies transmission in southeast china.the frequent occurrence of ferret badger-associated human rabies cases in southeast china highlights the lack of laboratory-based surveillance and urges revisiting the potential importance of this animal in rabies transmission. to determine if the ferret badgers actually contribute to human and dog rabies cases, and the possible origin of the ferret badger-associated rabies in the region, an active rabies survey was conducted to determine the frequency of rabies infection and seroprevalence in d ...201020691095
epidemiology of human rabies in south africa, 1983-2007.rabies remains a global public health problem but increasingly so in the developing world. given a lack of awareness, priority and diagnostic capability, very few developing countries, especially in africa, report on laboratory confirmed human rabies cases. here we present a retrospective study on the epidemiology of human rabies in republic of south africa for a 25-year period, 1983-2007, based on laboratory confirmed cases. the study highlights the role of the domestic dog as a reservoir and v ...201021036195
monosynaptic rabies virus reveals premotor network organization and synaptic specificity of cholinergic partition cells.movement is the behavioral output of neuronal activity in the spinal cord. motor neurons are grouped into motor neuron pools, the functional units innervating individual muscles. here we establish an anatomical rabies virus-based connectivity assay in early postnatal mice. we employ it to study the connectivity scheme of premotor neurons, the neuronal cohorts monosynaptically connected to motor neurons, unveiling three aspects of organization. first, motor neuron pools are connected to segmental ...201021040847
[construction and rescue of rabies virus mutant strain srv9].to construct a rabies virus mutant, the psi region was replaced by the coding region of human cytochrome c gene, and the coding region for cytoplasmic domain of glycoprotein g was deleted in the full-length of genomic cdna of rabies virus strain srv9. the mutant plasmid and the plasmids with n, p, l and g structural proteins of wild type srv9 were co-transfected into bhk-21 cells. it was shown by ifa that there were many specific fluorescence in the bhk-21 cells, and typical rabies virus virions ...201021043132
[expression and characterization of rabies virus nucleoprotein in baculovirus].to construct a recombinant expression plasmid bacmid-n containing the n gene of rabies virus, the n gene of rv cvs-11 strain was cloned into the baculovirus shuttle vector (bacmid). recombinant baculovirus acmnpv-n (p1 viral stock) was obtained by transfecting the bacmid-n into the insect cell line of sf9. the expressed nucleoprotein was identified and analysised by elisa, fa, sds-page and western blot assays. the results showed that the np protein was expressed intracellularly and had a good an ...201021043133
isolation and characterization of novel human monoclonal antibodies possessing neutralizing ability against rabies virus.rabies is a fatal viral encephalitis which is transmitted by exposure to the bite of rabid animals. human and equine rabies immunoglobulins are indispensable pharmacological agents for severe bite exposure, as is vaccine. however, several disadvantages, including limited supply, adverse reactions, and high cost, hamper their wide application in developing countries. in the present study, two novel humabs which neutralize rabies virus were established from vaccinated hyperimmune volunteers using ...201021044141
pathogenicity of different rabies virus isolates and protection test in vaccinated mice.this study was aimed to evaluate and compare the pathogenicity of rabies virus isolated from bats and dogs, and to verify the efficacy of a commercial rabies vaccine against these isolates. for evaluation of pathogenicity, mice were inoculated by the intramuscular route (im) with 500micld₅₀/0.03 ml of the viruses. the cross-protection test was performed by vaccinating groups of mice by the subcutaneous route and challenged through the intracerebral (ic) route. isolates were fully pathogenic when ...201021049225
epidemiology of vampire bat-transmitted rabies virus in goiás, central brazil: re-evaluation based on g-l intergenic region.abstract:201021059233
phylodynamics and human-mediated dispersal of a zoonotic virus.understanding the role of humans in the dispersal of predominantly animal pathogens is essential for their control. we used newly developed bayesian phylogeographic methods to unravel the dynamics and determinants of the spread of dog rabies virus (rabv) in north africa. each of the countries studied exhibited largely disconnected spatial dynamics with major geopolitical boundaries acting as barriers to gene flow. road distances proved to be better predictors of the movement of dog rabv than acc ...201021060816
rabies virus (rv) glycoprotein expression levels are not critical for pathogenicity of rv.previous comparisons of different rabies virus (rv) strains suggested an inverse relationship between pathogenicity and the amount of glycoprotein produced in infected cells. in order to provide more insight into this relationship, we pursued an experimental approach that allowed us to alter the glycoprotein expression level without altering the glycoprotein sequence, thereby eliminating the contribution of amino acid changes to differences in viral virulence. to this end, we constructed an infe ...201021068252
origins of multisynaptic projections from the basal ganglia to rostrocaudally distinct sectors of the dorsal premotor area in macaques.we examined the organization of multisynaptic projections from the basal ganglia (bg) to the dorsal premotor area in macaques. after injection of the rabies virus into the rostral sector of the caudal aspect of the dorsal premotor area (f2r) and the caudal sector of the caudal aspect of the dorsal premotor area (f2c), second-order neuron labeling occurred in the internal segment of the globus pallidus (gpi) and the substantia nigra pars reticulata (snr). labeled gpi neurons were found in the cau ...201021070393
emerging topics and new perspectives on hla-g.following the fifth international conference on non-classical hla-g antigens (hla-g), held in paris in july 2009, we selected some topics which focus on emerging aspects in the setting of hla-g functions. in particular, hla-g molecules could play a role in: (1) various inflammatory disorders, such as multiple sclerosis, intracerebral hemorrhage, gastrointestinal, skin and rheumatic diseases, and asthma, where they may act as immunoregulatory factors; (2) the mechanisms to escape immune surveilla ...201021080027
genetic dissection of interferon-antagonistic functions of rabies virus phosphoprotein: inhibition of interferon regulatory factor 3 activation is important for pathogenicity.the rabies virus (rv) phosphoprotein (p) is a type i interferon (ifn) antagonist preventing both transcriptional induction of ifn and ifn-mediated jak/stat signaling. in addition, p is an essential cofactor of the viral polymerase and is required for encapsidation of viral rna into nucleoprotein during replication. by site-directed mutagenesis, we have identified a domain of p required for efficient inhibition of ifn induction. phosphoproteins lacking amino acids (aa) 176 to 181, 182 to 186, or ...201021084487
a reverse-transcription, loop-mediated isothermal amplification assay for detection of bovine ephemeral fever virus in the blood of infected cattle.a novel reverse-transcription, loop-mediated isothermal amplification (rt-lamp) assay for the detection of bovine ephemeral fever virus (befv) was developed and evaluated in this study. the rt-lamp assay exhibited higher sensitivity when compared with conventional reverse-transcription polymerase chain reaction (rt-pcr) and virus isolation methods. the specificity of the assay was determined by digestion of the rt-lamp products with restriction enzyme and detection of befv serogroup rabies virus ...201021093487
rabies virus expressing dendritic cell-activating molecules enhances the innate and adaptive immune response to vaccination.our previous studies indicated that recruitment and/or activation of dendritic cells (dcs) is important in enhancing the protective immune responses against rabies virus (rabv) (l. zhao, h. toriumi, h. wang, y. kuang, x. guo, k. morimoto, and z. f. fu, j. virol. 84:9642-9648). to address the importance of dc activation for rabv vaccine efficacy, the genes for several dc recruitment and/or activation molecules, e.g., granulocyte-macrophage colony-stimulating factor (gm-csf), macrophage-derived ch ...201021106736
rabies virus strains circulating in bhutan: implications for control.summarywe report a molecular epidemiological study of rabies virus (rabv) strains circulating in animal populations in bhutan, and investigate potential origins of these viruses. twenty-three rabv isolates originating from dogs and other domestic animals were characterized by sequencing the partial nucleoprotein (n) gene (395 bp). phylogenetic analysis was conducted and the bhutanese isolates were compared with rabies viruses originating from other parts of the world. phylogenetic analysis showe ...201021108870
[molecular epidemiology investigation of rabies virus nucleoprotein genes in china].to study the relationship between the distribution of rabies virus and genetic variation, the genetic characterization and variation of rabies virus strains in china were analyzed.201021110419
[virus detection and viral location in brain tissue of sulking mice infected recombinant rabies virus by frozen section].to observe the existence and location of the recombinant rabies virus in the hippocampus of the sulking mice infected recombinant rabies virus.201021110420
[analysis of human rabies high-occurrence factors in guangxi from 2004 to 2008].analysis the epidemiological characteristics on rabies cases occurred in guangxi from 2004 to 2008 and summarize the result of healthy-dog infection rabies virus investigation from 2006 to 2008. exploring the high-occurrence and correlated factors on rabies in guangxi.201021110421
[the comparison of the who standard rabies immunoglobulin and the national standard human rabies immunoglobulin used in the rapid fluorescent focus inhibition test (rffit)].compare the difference of the results referred to the who standard rabies immunoglobulin and the national standard human rabies immunoglobulin used in the rapid fluorescent focus inhibition test (rffit).201021110422
monosynaptic circuit tracing in vivo through cre-dependent targeting and complementation of modified rabies virus.we describe a powerful system for revealing the direct monosynaptic inputs to specific cell types in cre-expressing transgenic mice through the use of cre-dependent helper virus and a modified rabies virus. we generated helper viruses that target gene expression to cre-expressing cells, allowing us to control initial rabies virus infection and subsequent monosynaptic retrograde spread. investigators can use this system to elucidate the connections onto a desired cell type in a high-throughput ma ...201021115815
comparison of reverse transcription loop-mediated isothermal amplification, conventional pcr and real-time pcr assays for japanese encephalitis virus.we developed and evaluated a reverse transcription loop-mediated isothermal amplification (rt-lamp) assay for detecting japanese encephalitis virus (jev). the sensitivity of the jev rt-lamp assay was in concordance with that of real-time rt-pcr and 10-fold more sensitive than that of conventional rt-pcr, which the detection limit was 24 copies/μl. the jev rt-lamp was highly specific, which no cross-reactivity was found with dengue-2 virus, rabies virus, norovirus, astrovirus and human enteroviru ...201021116858
rabies virus rna in naturally infected vampire bats, northeastern brazil. 201021122246
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