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reinvestigating the role of igm in rabies virus postexposure vaccination.b cells secreting igg antibodies, but not igm, are thought to be solely responsible for vaccine-induced protection against rabies virus (rabv) infections in postexposure settings. in this report, we reinvestigated the potential for igm to mediate protection in a mouse model of rabv vaccination. immunocompetent mice immunized with an experimental live replication-deficient rabv-based vaccine produced virus neutralizing antibodies (vnas) within 3 days of vaccination. however, mice unable to produc ...201323760250
presence of cross-reactions with other viral encephalitides in the indirect fluorescent-antibody test for diagnosis of rabies.the antemortem diagnosis of rabies in humans employs techniques that require accuracy, speed, and sensitivity. a combination of histochemical analysis, in vitro virus isolation, immunological methods, and molecular amplification procedures are utilized in efforts to diagnose the disease. modern medicine now offers potentially life-saving treatment for a disease that was considered invariably fatal once clinical signs develop. however, medical intervention efforts require a rapid and accurate dia ...201324088851
molecular evolutionary signatures reveal the role of host ecological dynamics in viral disease emergence and spread.rna viruses account for numerous emerging and perennial infectious diseases, and are characterized by rapid rates of molecular evolution. the ecological dynamics of most emerging rna viruses are still poorly understood and difficult to ascertain. the availability of genome sequence data for many rna viruses, in principle, could be used to infer ecological dynamics if changes in population numbers produced a lasting signature within the pattern of genome evolution. as a result, the rapidly emergi ...201323382419
rabies in iraq: trends in human cases 2001-2010 and characterisation of animal rabies strains from baghdad.control of rabies requires a consistent supply of dependable resources, constructive cooperation between veterinary and public health authorities, and systematic surveillance. these are challenging in any circumstances, but particularly during conflict. here we describe available human rabies surveillance data from iraq, results of renewed sampling for rabies in animals, and the first genetic characterisation of circulating rabies strains from iraq. human rabies is notifiable, with reported case ...201323469303
a step forward in molecular diagnostics of lyssaviruses--results of a ring trial among european laboratories.rabies is a lethal and notifiable zoonotic disease for which diagnostics have to meet the highest standards. in recent years, an evolution was especially seen in molecular diagnostics with a wide variety of different detection methods published. therefore, a first international ring trial specifically designed on the use of reverse transcription polymerase chain reaction (rt-pcr) for detection of lyssavirus genomic rna was organized. the trial focussed on assessment and comparison of the perform ...201323520505
membrane and inclusion body targeting of lyssavirus matrix proteins.lyssavirus matrix proteins (m) support virus budding and have accessory functions that may contribute to host cell manipulation and adaptation to specific hosts. here, we show that rabies virus (rabv) and european bat lyssavirus type 1 (eblv-1) m proteins differ in targeting and accumulation at cellular membranes. in contrast to rabv m, eblv-1 m expressed from authentic eblv-1 or chimeric rabv accumulated at the golgi apparatus. chimeric m proteins revealed that golgi association depends on the ...201323046288
plant-derived pharmaceuticals for the developing world.plant-produced vaccines and therapeutic agents offer enormous potential for providing relief to developing countries by reducing the incidence of infant mortality caused by infectious diseases. vaccines derived from plants have been demonstrated to effectively elicit an immune response. biopharmaceuticals produced in plants are inexpensive to produce, require fewer expensive purification steps, and can be stored at ambient temperatures for prolonged periods of time. as a result, plant-produced b ...201323857915
antibody quality and protection from lethal ebola virus challenge in nonhuman primates immunized with rabies virus based bivalent vaccine.we have previously described the generation of a novel ebola virus (ebov) vaccine platform based on (a) replication-competent rabies virus (rabv), (b) replication-deficient rabv, or (c) chemically inactivated rabv expressing ebov glycoprotein (gp). mouse studies demonstrated safety, immunogenicity, and protective efficacy of these live or inactivated rabv/ebov vaccines. here, we evaluated these vaccines in nonhuman primates. our results indicate that all three vaccines do induce potent immune re ...201323737747
host-rabies virus protein-protein interactions as druggable antiviral targets.we present an unconventional approach to antiviral drug discovery, which is used to identify potent small molecules against rabies virus. first, we conceptualized viral capsid assembly as occurring via a host-catalyzed biochemical pathway, in contrast to the classical view of capsid formation by self-assembly. this suggested opportunities for antiviral intervention by targeting previously unappreciated catalytic host proteins, which were pursued. second, we hypothesized these host proteins to be ...201323404707
comparison of pathogenic domains of rabies and african rabies-related lyssaviruses and pathogenicity observed in mice.several lyssavirus species occur in africa (rabies virus, lagos bat virus, mokola virus, duvenhage virus, shimoni bat virus and ikoma lyssavirus), displaying a high sequence diversity between isolates belonging to the same species. there is limited information about comparative pathogenesis of these african lyssaviruses and this precludes authoritative opinion on the potential public and veterinary health impact. in this study, an analysis of representative african lyssaviruses attempted to corr ...201323718883
highly efficient retrograde gene transfer into motor neurons by a lentiviral vector pseudotyped with fusion glycoprotein.the development of gene therapy techniques to introduce transgenes that promote neuronal survival and protection provides effective therapeutic approaches for neurological and neurodegenerative diseases. intramuscular injection of adenoviral and adeno-associated viral vectors, as well as lentiviral vectors pseudotyped with rabies virus glycoprotein (rv-g), permits gene delivery into motor neurons in animal models for motor neuron diseases. recently, we developed a vector with highly efficient re ...201324086660
comparison of heterologous prime-boost strategies against human immunodeficiency virus type 1 gag using negative stranded rna viruses.this study analyzed a heterologous prime-boost vaccine approach against hiv-1 using three different antigenically unrelated negative-stranded viruses (nsv) expressing hiv-1 gag as vaccine vectors: rabies virus (rabv), vesicular stomatitis virus (vsv) and newcastle disease virus (ndv). we hypothesized that this approach would result in more robust cellular immune responses than those achieved with the use of any of the vaccines alone in a homologous prime-boost regimen. to this end, we primed bal ...201323840600
evaluation of rabies biologics against irkut virus isolated in china.an irkut virus (irkv) was recently isolated from a bat in china. the protective ability of rabies biologics available in the chinese market and experimental biologics against the rabies virus (rabv) and irkv were assessed in a hamster model via preexposure prophylaxis (prep) and postexposure prophylaxis (pep) experiments. the results demonstrated that a single dose of rabies vaccine did not induce adequate protection against irkv infection. however, routine prep with three doses of vaccine induc ...201323946522
isolation of irkut virus from a murina leucogaster bat in china.bats are recognized as a major reservoir of lyssaviruses; however, no bat lyssavirus has been isolated in asia except for aravan and khujand virus in central asia. all chinese lyssavirus isolates in previous reports have been of species rabies virus, mainly from dogs. following at least two recent bat-associated human rabies-like cases in northeast china, we have initiated a study of the prevalence of lyssaviruses in bats in jilin province and their public health implications. a bat lyssavirus h ...201323505588
biochemical and structural studies of the oligomerization domain of the nipah virus phosphoprotein: evidence for an elongated coiled-coil homotrimer.nipah virus (niv) is a recently emerged severe human pathogen that belongs to the henipavirus genus within the paramyxoviridae family. the niv genome is encapsidated by the nucleoprotein (n) within a helical nucleocapsid that is the substrate used by the polymerase for transcription and replication. the polymerase is recruited onto the nucleocapsid via its cofactor, the phosphoprotein (p). the niv p protein has a modular organization, with alternating disordered and ordered domains. among these ...201324074578
aptamer-based therapeutics: new approaches to combat human viral diseases.viruses replicate inside the cells of an organism and continuously evolve to contend with an ever-changing environment. many life-threatening diseases, such as aids, sars, hepatitis and some cancers, are caused by viruses. because viruses have small genome sizes and high mutability, there is currently a lack of and an urgent need for effective treatment for many viral pathogens. one approach that has recently received much attention is aptamer-based therapeutics. aptamer technology has high targ ...201324287493
human contacts with oral rabies vaccine baits distributed for wildlife rabies management--ohio, 2012.baits laden with oral rabies vaccines are important for the management of wildlife rabies in the united states. in august 2012, the wildlife services program of the u.s. department of agriculture's animal and plant health inspection service began a field trial involving limited distribution of a new oral rabies vaccine bait in five states, including ohio. the vaccine consisted of live recombinant human adenovirus type 5 vector, expressing rabies virus glycoprotein (adrg1.3) (onrab). a previously ...201323575240
rabies virus is recognized by the nlrp3 inflammasome and activates interleukin-1β release in murine dendritic cells.inflammasome activation is important for the development of an effective host defense against many pathogens, including rna viruses. however, the mechanism by which the inflammasome recognizes rna viruses and its role in rabies virus (rabv) pathogenicity and immunogenicity remain poorly defined. to determine the function of the inflammasome in response to rabv infection, we infected murine bone marrow-derived dendritic cells (bmdcs) with rabv. our results indicate that the infection of bmdcs wit ...201323487464
in vitro and in vivo inhibition of rabies virus replication by rna interference.rabies is a zoonotic disease that affects all mammals and leads to more than 55,000 human deaths every year, caused by rabies virus (rabv) (mononegavirales: rhabdoviridae: lyssavirus). currently, human rabies treatment is based on the milwaukee protocol which consists on the induction of coma and massive antiviral therapy. the aim of this study was to assess the decrease in the titer of rabies virus both in vitro and in vivo using short-interfering rnas. to this end, three sirnas were used with ...201324516427
establishment and preliminary application of a rapid fluorescent focus inhibition test (rffit) for rabies virus.the world health organization (who) standard assay for determining levels of the rabies virus neutralization antibody (rvna) is the rapid fluorescent focus inhibition test (rffit), which is used to evaluate the immunity effect after vaccination against rabies. for rffit, cvs-11 was used as the challenge virus, bsr cells as the adapted cells, and who rabies immunoglobulin (who std) as the reference serum in this study. with reference to who and pasteur rffit procedures, a micro-rffit procedure ad ...201323913179
climate change and infectious diseases in the arctic: establishment of a circumpolar working group.the arctic, even more so than other parts of the world, has warmed substantially over the past few decades. temperature and humidity influence the rate of development, survival and reproduction of pathogens and thus the incidence and prevalence of many infectious diseases. higher temperatures may also allow infected host species to survive winters in larger numbers, increase the population size and expand their habitat range. the impact of these changes on human disease in the arctic has not bee ...201425317383
viral aetiology of central nervous system infections in adults admitted to a tertiary referral hospital in southern vietnam over 12 years.central nervous system (cns) infections are important diseases in both children and adults worldwide. the spectrum of infections is broad, encompassing bacterial/aseptic meningitis and encephalitis. viruses are regarded as the most common causes of encephalitis and aseptic meningitis. better understanding of the viral causes of the diseases is of public health importance, in order to better inform immunization policy, and may influence clinical management.201425165820
enhancement of blood-brain barrier permeability and reduction of tight junction protein expression are modulated by chemokines/cytokines induced by rabies virus infection.infection with laboratory-attenuated rabies virus (rabv) enhances blood-brain barrier (bbb) permeability, which has been demonstrated to be an important factor for host survival, since it allows immune effectors to enter the central nervous system (cns) and clear rabv. to probe the mechanism by which rabv infection enhances bbb permeability, the expression of tight junction (tj) proteins in the cns was investigated following intracranial inoculation with laboratory-attenuated or wild-type (wt) r ...201424522913
an anterograde rabies virus vector for high-resolution large-scale reconstruction of 3d neuron morphology.glycoprotein-deleted rabies virus (rabv ∆g) is a powerful tool for the analysis of neural circuits. here, we demonstrate the utility of an anterograde rabv ∆g variant for novel neuroanatomical approaches involving either bulk or sparse neuronal populations. this technology exploits the unique features of rabv ∆g vectors, namely autonomous, rapid high-level expression of transgenes, and limited cytotoxicity. our vector permits the unambiguous long-range and fine-scale tracing of the entire axonal ...201424723034
rabies virus envelope glycoprotein targets lentiviral vectors to the axonal retrograde pathway in motor neurons.rabies pseudotyped lentiviral vectors have great potential in gene therapy, not least because of their ability to transduce neurons following their distal axonal application. however, very little is known about the molecular processes that underlie their retrograde transport and cell transduction. using multiple labeling techniques and confocal microscopy, we demonstrated that pseudotyping with rabies virus envelope glycoprotein (rv-g) enabled the axonal retrograde transport of two distinct subt ...201424753246
[guidelines for antifungal prophylaxis, diagnosis and therapy in pediatric hematology and oncology - a review of literature and expert recommendations].problems with importing non-registered medicines for treating rare life-threatening infectious diseases led to establishment of the emergency anti-infective drug reserve (eaidr) for the czech republic.201425702289
[emergency reserve of life-saving anti-infective drugs].problems with importing non-registered medicines for treating rare life-threatening infectious diseases led to establishment of the emergency anti-infective drug reserve (eaidr) for the czech republic.201425135139
production and characterization of a fusion peptide derived from the rabies virus glycoprotein (rvg29).gene therapy targeting the brain holds great promise in curing nervous system degenerative diseases in clinical applications. with this in mind, in a previous study a 29 amino-acid peptide derived from the rabies virus glycoprotein (rvg29) with a nonamer stretch of arginine residues (rvg29-9r) at its carboxy-terminus was exploited as a ligand for brain-targeting gene delivery. importantly, the report demonstrated that the rvg29-9r vector was able to cross the blood-brain barrier. rvg29-9r is cur ...201425218147
hierarchically self-organized monolithic nanoporous membrane for excellent virus enrichment.enrichment of viruses is essential for making high dose viral stocks for vaccines and virus-related research. since the widely used ultracentrifugation for concentrating viral stock requires ultra-high speed rotation, it easily destroys the activity of some viruses, for instance, hepatitis c virus (hcv), which has a fragile structure and low virus titer. we introduce a novel method to concentrate hcv virus in stock by using a hierarchically self-organized monolithic nanoporous membrane made by s ...201424354273
tail vaccination in cats: a pilot study.feline injection site sarcomas affect 1-10 cats per every 10,000 vaccinated and are associated with high mortality. radical resection may be curative, but is often associated with prolonged recovery, disfigurement and loss of function when tumors occur at currently recommended injection sites. the objective of this study was to assess alternatives to currently recommended vaccination sites in terms of preference by oncology practitioners, ease of injection and serological responses. surgical, ra ...201424108201
european bats as carriers of viruses with zoonotic potential.bats are being increasingly recognized as reservoir hosts of highly pathogenic and zoonotic emerging viruses (marburg virus, nipah virus, hendra virus, rabies virus, and coronaviruses). while numerous studies have focused on the mentioned highly human-pathogenic bat viruses in tropical regions, little is known on similar human-pathogenic viruses that may be present in european bats. although novel viruses are being detected, their zoonotic potential remains unclear unless further studies are con ...201425123684
rabies and rabies virus in wildlife in mainland china, 1990-2013.the number of wildlife rabies and wildlife-associated human and livestock rabies cases has increased in recent years, particularly in the southeast and northeast regions of mainland china. to better understand wildlife rabies and its role in human and livestock rabies, we reviewed what is known about wildlife rabies from the 1990s to 2013 in mainland china. in addition, the genetic diversity and phylogeny of available wildlife-originated rabies viruses (rabvs) were analyzed. several wildlife spe ...201424911887
early diagnosis of irkut virus infection using magnetic bead-based serum peptide profiling by maldi-tof ms in a mouse model.early diagnosis is important for the prompt post-exposure prophylaxis of lyssavirus infections. to diagnose irkut virus (irkv) infection during incubation in mice, a novel method using magnetic bead-based serum peptide profiling by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (maldi-tof ms) has been established. for this test, serum peptides were concentrated by adsorption to and elution from the magnetic bead-based weak cation ion exchanger. mass spectrograms obt ...201424670473
raccoonpoxvirus safety in immunocompromised and pregnant mouse models.numerous poxviruses infect humans and animal hosts, and a poxvirus vaccine with an improved safety profile is needed as the current vaccinia virus vaccine is contraindicated in individuals that have a history of eczema or heart disease, or are immunocompromised or pregnant. in addition, poxviruses make excellent vaccine vectors for other infectious diseases and cancer. raccoonpoxvirus is a naturally occurring attenuated north american poxvirus, and thus it is of interest as a vaccine vector plat ...201424837508
[rl-rvg inhibits proliferation and promotes apoptosis of lung cancer cells in vitro].to infect lung adenocarcinoma a549 cells with recombinant lasota strain newcastle disease virus (ndv) vaccine expressing the rabies virus glycoprotein (rl-rvg), and explore the effect of rl-rvg on proliferation and apoptosis of lung cancer cells.201424796735
antigenic characterisation of lyssaviruses in south africa.there are at least six lyssavirus species that have been isolated in africa, which include classical rabies virus, lagos bat virus, mokola virus, duvenhage virus, shimoni bat virus and ikoma lyssavirus. in this retrospective study, an analysis of the antigenic reactivity patterns of lyssaviruses in south africa against a panel of 15 anti-nucleoprotein monoclonal antibodies was undertaken. a total of 624 brain specimens, collected between 2005 and 2009, confirmed as containing lyssavirus antigen ...201425685866
interaction of rabies virus p-protein with stat proteins is critical to lethal rabies disease.rabies virus (rabv) causes rabies disease resulting in >55,000 human deaths/year. the multifunctional rabv p-protein has essential roles in genome replication, and forms interactions with cellular stat proteins that are thought to underlie viral antagonism of interferon-dependent immunity. however, the molecular details of p-protein-stat interaction, and its importance to disease are unresolved.201424367042
a single immunization with recombinant rabies virus (erag3g) confers complete protection against rabies in mice.new alternative bait rabies vaccines applicable to pet dogs and wild animals are needed to eradicate rabies in korea. in this study, recombinant rabies virus, erag3g strain was constructed using reverse genetic system and the safety, efficacy and immunogenicity of the erag3g strain was evaluated in mice and dogs.201425003091
health evaluation and survey of zoonotic pathogens in free-ranging capybaras (hydrochoerus hydrochaeris).capybaras (hydrochoerus hydrochaeris) are the world's largest rodents and play an epidemiologic role in the transmission of zoonotic pathogens, including the causative agents of brazilian spotted fever, leptospirosis, and others. we surveyed the health of 31 free-ranging capybaras at the alberto löfgren state park, são paulo, brazil using a variety of diagnostic methods. hematology and serum chemistry were consistent with mild malnutrition and parasitism but did not indicate severe physiologic i ...201424779462
innate antiviral signalling in the central nervous system.the innate immune system mediates protection against neurotropic viruses capable of infecting the central nervous system (cns). neurotropic viruses include herpes simplex virus (hsv), west nile virus (wnv), rabies virus, la crosse virus, and poliovirus. viral infection triggers activation of pattern recognition receptors (prrs) such as toll-like receptors (tlrs), retinoic acid-inducible gene 1 (rig-i) like receptors (rlrs), nucleotide-binding oligomerization domain (nod)-like receptors (nlrs), a ...201424316012
molecular double-check strategy for the identification and characterization of european lyssaviruses.the "gold standard" for post-mortem rabies diagnosis is the direct fluorescent antibody test (fat). however, in the case of ante-mortem non-neural sample material or decomposed tissues, the fat reaches its limit, and the use of molecular techniques can be advantageous. in this study, we developed and validated a reverse transcription pcr cascade protocol feasible for the classification of samples, even those for which there is no epidemiological background knowledge. this study emphasises on the ...201424681051
interferon-induced protein ifit2 protects mice from infection of the peripheral nervous system by vesicular stomatitis virus.the interferon system provides the first line of host defense against virus infection. mouse pathogenesis studies have revealed the importance of specific interferon-induced proteins in providing protection against specific viruses. we have previously reported that one such protein, ifit2, protects neurons of the central nervous system from intranasal infection by the neurotropic rhabdovirus, vesicular stomatitis virus (vsv). here, we demonstrate that ifit2 protects the peripheral nervous system ...201424991014
met-ccl5 represents an immunotherapy strategy to ameliorate rabies virus infection.infection of rabies virus (rabv) causes central nervous system (cns) dysfunction and results in high mortality in human and animals. however, it is still unclear whether and how cns inflammation and immune response contribute to rabv infection.201425182681
variability in seroprevalence of rabies virus neutralizing antibodies and associated factors in a colorado population of big brown bats (eptesicus fuscus).in 2001-2005 we sampled permanently marked big brown bats (eptesicus fuscus) at summer roosts in buildings at fort collins, colorado, for rabies virus neutralizing antibodies (rvna). seroprevalence was higher in adult females (17.9%, n = 2,332) than males (9.4%, n = 128; p = 0.007) or volant juveniles (10.2%, n = 738; p<0.0001). seroprevalence was lowest in a drought year with local insecticide use and highest in the year with normal conditions, suggesting that environmental stress may suppress ...201424465996
targeting dna vaccines to myeloid cells using a small peptide.targeting dna vaccines to dendritic cells (dcs) greatly enhances immunity. although several approaches have been used to target protein ags to dcs, currently there is no method that targets dna vaccines directly to dcs. here, we show that a small peptide derived from the rabies virus glycoprotein fused to protamine residues (rvg-p) can target dna to myeloid cells, including dcs, which results in enhanced humoral and t-cell responses. dcs targeted with a dna vaccine encoding the immunodominant va ...201425270431
expression of neuronal cxcl10 induced by rabies virus infection initiates infiltration of inflammatory cells, production of chemokines and cytokines, and enhancement of blood-brain barrier permeability.it has been shown that enhancement of blood-brain barrier (bbb) permeability is modulated by the expression of chemokines/cytokines and reduction of tight junction (tj) proteins in the brains of mice infected with rabies virus (rabv). since cxcl10 was found to be the most highly expressed chemokine, its temporal and spatial expression were determined in the present study. the expression of the chemokine cxcl10 was initially detected in neurons as early as 3 days postinfection (p.i.) in the brain ...201425339777
establishment of myotis myotis cell lines--model for investigation of host-pathogen interaction in a natural host for emerging viruses.bats are found to be the natural reservoirs for many emerging viruses. in most cases, severe clinical signs caused by such virus infections are normally not seen in bats. this indicates differences in the virus-host interactions and underlines the necessity to develop natural host related models to study these phenomena. due to the strict protection of european bat species, immortalized cell lines are the only alternative to investigate the innate anti-virus immune mechanisms. here, we report ab ...201425295526
serosurvey for selected pathogens in free-ranging american black bears (ursus americanus) in maryland, usa.american black bears (ursus americanus) in maryland, usa, live in forested areas in close proximity to humans and their domestic pets. from 1999 to 2011, we collected 84 serum samples from 63 black bears (18 males; 45 females) in five maryland counties and tested them for exposure to infectious, including zoonotic, pathogens. a large portion of the bears had antibody to canine distemper virus and toxoplasma gondii, many at high titers. prevalences of antibodies to zoonotic agents such as rabies ...201425075540
using open-access taxonomic and spatial information to create a comprehensive database for the study of mammalian and avian livestock and pet infections.what are all the species of pathogen that affect our livestock? as 6 out of every 10 human pathogens came from animals, with a good number from livestock and pets, it seems likely that the majority that emerge in the future, and which could threaten or devastate human health, will come from animals. only 10 years ago, the first comprehensive pathogen list was compiled for humans; we still have no equivalent for animals. here we describe the creation of a novel pathogen database, and present outp ...201423906393
first report of angiostrongylus vasorum and hepatozoon from a red fox (vulpes vulpes) from west virginia, usa.angiostrongylus vasorum was identified in the lungs of a red fox (vulpes vulpes) from west virginia, united states (us), indicating a new geographical location for this metastrongylid nematode. the fox was euthanized and submitted for necropsy after displaying erratic behavior. we did not detect rabies virus or canine distemper virus from the fox. we observed bronchopneumonia associated with a. vasorum infection disseminated in both lungs. in addition, protozoal meronts were observed in the live ...201424412356
assessment of packed bed bioreactor systems in the production of viral vaccines.vaccination is believed to be the most effective method for the prevention of infectious diseases. thus it is imperative to develop cost effective and scalable process for the production of vaccines so as to make them affordable for mass use. in this study, performance of a novel disposable icellis fixed bed bioreactor system was investigated for the production of some viral vaccines like rabies, hepatitis-a and chikungunya vaccines in comparison to conventional systems like the commercially ava ...201424949260
twenty year experience of the oral rabies vaccine sag2 in wildlife: a global review.the sag2 vaccine (rabigen® sag2) is a modified live attenuated rabies virus vaccine, selected from the sad bern strain in a two-step process of amino acid mutation using neutralizing monoclonal antibodies. the strain is genetically stable and does not spread in vivo or induce a persistent infection. its absence of residual pathogenicity was extensively demonstrated in multiple target and non target species (such as wild carnivores and rodent species), including non-human primates. the efficacy o ...201425106552
comparison of biotinylated monoclonal and polyclonal antibodies in an evaluation of a direct rapid immunohistochemical test for the routine diagnosis of rabies in southern africa.the major etiological agent of rabies, rabies virus (rabv), accounts for tens of thousands of human deaths per annum. the majority of these deaths are associated with rabies cycles in dogs in resource-limited countries of africa and asia. although routine rabies diagnosis plays an integral role in disease surveillance and management, the application of the currently recommended direct fluorescent antibody (dfa) test in countries on the african and asian continents remains quite limited. a novel ...201425254652
cross-neutralization of antibodies induced by vaccination with purified chick embryo cell vaccine (pcecv) against different lyssavirus species.rabies is a neglected zoonotic disease caused by viruses belonging to the genus lyssavirus. in endemic countries of asia and africa, where the majority of the estimated 60,000 human rabies deaths occur, it is mainly caused by the classical rabies virus (rabv) transmitted by dogs. over the last decade new species within the genus lyssavirus have been identified. meanwhile 15 (proposed or classified) species exist, including australian bat lyssavirus (ablv), european bat lyssavirus (eblv-1 and -2) ...201425483634
recent observations on australian bat lyssavirus tropism and viral entry.australian bat lyssavirus (ablv) is a recently emerged rhabdovirus of the genus lyssavirus considered endemic in australian bat populations that causes a neurological disease in people indistinguishable from clinical rabies. there are two distinct variants of ablv, one that circulates in frugivorous bats (genus pteropus) and the other in insectivorous microbats (genus saccolaimus). three fatal human cases of ablv infection have been reported, the most recent in 2013, and each manifested as acute ...201424556791
molecular characterization of encephalitic bovine listeriosis from southern brazil.reports of bovine listeriosis in brazil are uncommon, being restricted to citations within retrospective studies, resulting in scarce documented information of this important disease of cattle. this manuscript describes the molecular findings associated with spontaneous encephalitic listeriosis in two steers from distinct herds within the state of paraná, southern brazil. both animals demonstrated altered consciousness suggestive of brain stem dysfunctions and died a few days after the initial o ...201423832703
rabies-virus-glycoprotein-pseudotyped recombinant baculovirus vaccine confers complete protection against lethal rabies virus challenge in a mouse model.rabies virus has been an ongoing threat to humans and animals. here, we developed a new strategy to generate a rabies virus vaccine based on a pseudotyped baculovirus. the recombinant baculovirus (bv-rvg/rvg) was pseudotyped with the rabies virus glycoprotein (rvg) and also simultaneously expressed another rvg under the control of the immediate early cmv promoter. in vitro, this rvg-pseudotyped baculovirus vector induced syncytium formation in insect cells and displayed more efficient gene deliv ...201424793501
development of a reverse genetics system for the ag strain of rabies virus in china.the ag rabies virus strain has been attenuated through multiple passages in cells and is now used as a vaccine strain in china. we attempted to develop a reverse genetics system using the ag strain. recombinant full-length genomic cdna was flanked by a hammerhead ribozyme and the hepatitis delta virus ribozyme. three helper plasmids encoding the nucleoprotein, the phosphoprotein, and the large protein were produced and introduced together with a plasmid containing the full-length ag viral genome ...201424272786
experimental oral immunization of ferret badgers (melogale moschata) with a recombinant canine adenovirus vaccine cav-2-e3δ-rgp and an attenuated rabies virus srv9.ferret badgers (melogale moschata) are a major reservoir of rabies virus in southeastern china. oral immunization has been shown to be a practical method for wildlife rabies management in europe and north america. two groups of 20 ferret badgers were given a single oral dose of a recombinant canine adenovirus-rabies vaccine, cav-2-e3δ-rgp, or an experimental attenuated rabies virus vaccine, srv9. at 21 days, all ferret badgers had seroconverted, with serum virus-neutralizing antibodies ranging f ...201424506428
recombinant rabies virus expressing the h protein of canine distemper virus protects dogs from the lethal distemper challenge.the rabies virus (rv) vector lbnse expressing foreign antigens have shown considerable promise as vaccines against viral and bacteria diseases, which is effective and safe. we produced a new rv-based vaccine vehicle expressing 1.824 kb hemagglutinin (h) gene of the canine distemper virus (cdv) by reverse genetics technology. the recombinant virus lbnse-cdv-h retained growth properties similar to those of vector lbnse both in bsr and mna cell culture. the h gene of cdv was expressed and detected ...201425465178
serologic survey for cross-species pathogens in urban coyotes (canis latrans), colorado, usa.abstract as coyotes (canis latrans) adapt to living in urban environments, the opportunity for cross-species transmission of pathogens may increase. we investigated the prevalence of antibodies to pathogens that are either zoonotic or affect multiple animal species in urban coyotes in the denver metropolitan area, colorado, usa, in 2012. we assayed for antibodies to canine parvovirus-2, canine distemper virus, rabies virus, toxoplasma gondii, yersinia pestis, and serotypes of leptospira interrog ...201425121408
selection of an aptamer against rabies virus: a new class of molecules with antiviral activity.rabies is a fatal central nervous system (cns) disease caused by the neurotropic rabies virus (rabv). the therapeutic management of rabv infections is still problematic, and novel antiviral strategies are urgently required. we established the rvg-bhk-21 cell line, which expresses rabv glycoprotein on the cell surface, to select aptamers. through 28 iterative rounds of selection, single-stranded dna (ssdna) aptamers were generated by exponential enrichment (selex). a virus titer assay and a real- ...201424486485
immunology of bats and their viruses: challenges and opportunities.bats are reservoir hosts of several high-impact viruses that cause significant human diseases, including nipah virus, marburg virus and rabies virus. they also harbor many other viruses that are thought to have caused disease in humans after spillover into intermediate hosts, including sars and mers coronaviruses. as is usual with reservoir hosts, these viruses apparently cause little or no pathology in bats. despite the importance of bats as reservoir hosts of zoonotic and potentially zoonotic ...201425494448
[not available].important preventive measures carried out in the herds of domestic animals have found improving the health status of farms, particularly for contagious diseases subject to mandatory declaration and accompanying drastic but necessary eradication measures in infected flocks. however it is more difficult to apply these same biosecurity measures on wildlife that may have been contaminated or not by domestic animals. the growing number of emerging infectious diseases of wildlife may reflect increased ...201427120911
improved transduction efficiency of a lentiviral vector for neuron-specific retrograde gene transfer by optimizing the junction of fusion envelope glycoprotein.the vector for neuron-specific retrograde gene transfer (neuret) is a pseudotype of human immunodeficiency virus type 1 (hiv-1)-based vector with fusion glycoprotein type c (fug-c), which consists of the n-terminal region of the extracellular domain of rabies virus glycoprotein (rvg) and the membrane-proximal region of the extracellular domain and the transmembrane/cytoplasmic domains of vesicular stomatitis virus glycoprotein (vsvg). the neuret vector shows a high efficiency of gene transfer th ...201424613797
rabies virus glycoprotein and immune response pattern using recombinant protein or recombinant rna viral vectors.the present study shows the humoral and cellular aspects of immune response generated by a recombinant rabies virus glycoprotein (rrvgp) as compared to those generated by viral vector carrying the rna coding for this protein (rvgp-rna). the rrvgp was synthesized by stably transfected drosophila melanogaster schneider 2 (s2) cells and the rvgp-rna was carried by a recombinant semiliki forest virus (sfv-rvgp). the data show that protein as well as the rna vaccine was capable of inducing reasonably ...201424598721
comparison of safety and immunogenicity of pvrv and pcecv immunized in patients with who category ii animal exposure: a study based on different age groups.the aim of this study was to compare the safety and immunogenicity between purified vero cell rabies vaccine (pvrv) and purified chick embryo cell vaccine (pcecv) in patients with who category ii animal exposure, especially in different age groups.201425522244
alterations in brain cerebral cortex proteome of rabies-infected cat.comparative proteome analysis using brain cerebral cortex tissues from cats and dogs infected with/without rabies virus were conducted using both two-dimensional gel-electrophoresis (2-de) and 2-d fluorescence difference gel- electrophoresis (2d-dige) methods. the 2-de gel images of all samples revealed >1,000 protein spots in each gel. quantitative intensity analysis revealed the same overall protein pattern in certain regions of the gel, but the rabies-infected brains exhibited more protein sp ...201425507598
laboratory data of dog rabies in southern cameroon from 2010 to 2013.dog rabies is endemic in most african countries and the risk of human rabies is estimated to be high in cameroon according to who estimations in 2010. this study aimed to describe the circulation rabies virus (rabv) among dogs in the southern regions of cameroon from 2010 to 2013 in a context, where mass vaccination campaigns are launched annually in order to control rabies in domestic animals including dogs and cats.201425495597
cell culture extraction and purification of rabies virus nucleoprotein.rabies is a major zoonotic viral disease and is detected using the world health organization standard diagnostic techniques. rabies detection is preferably done using the fluorescent antibody technique (fat) that provides reliable diagnosis with almost 100% accuracy for all variant strains, if a proper conjugate is used. rabies virus nucleoprotein (np) is the most important protein used in production of a specific diagnostic conjugate.201425485056
severe abdominal pain as the first manifestation of rabies.rabies is an acute fatal viral disease that is generally transmitted from animals to humans following wild and domestic animal bites. the rabies virus enters the body from the area where the individual is bitten, and then the virus moves towards the brain and involves the nerves.201425485053
a randomized open-labeled study to demonstrate the non-inferiority of purified chick-embryo cell rabies vaccine administered in the zagreb regimen (2-1-1) compared with the essen regimen in chinese adults.the zagreb regimen has been used for 20 years in various countries. in china, until 2010, the zagreb schedule was only approved for purified chick embryo cell vaccine (pcecv) and purified vero cell rabies vaccines (pvrv). in this phase iii clinical trial, we aimed to demonstrate the safety and immunogenic non-inferiority of the zagreb regimen compared with the essen regimen in healthy adult chinese immunized with pcecv (rabipur®). the study enrolled 825 subjects aged 18 to 50 years; serum sample ...201425483635
gene order rearrangement of the m gene in the rabies virus leads to slower replication.the matrix protein (m) is one of only five genes in the rv genome and is an important multifunctional protein. besides to allow for the release of newly replicated virions pairing with g, the m protein also functions in virus replication, pathogenicity, and host cell apoptosis. the goal of present study is to generate recombinant viruses with m gene rearranged, thus laying the foundation for further exploring what will happen when the gene for m is relocated on the rv single-strand rna. we used ...201425674605
effect of corticosteroids on rvna production of a patient with acute disseminated encephalomyelitis following rabies vaccination as well as administration of hrig.it has not been reported that administration of combining rabies vaccines and immunoglobulin resulted in acute disseminated encephalomyelitis (adem) yet. this report described that an old man acquired adem after being administrated with purified vero cell rabies vaccine (pvrv) and human rabies immunoglobulin (hrig). then he was given intravenous and oral glucocorticoids. simultaneously, rabies vaccination was continued with purified chick embryo cell vaccines (pcecv) instead of pvrv. furthermore ...201425668669
alterations in brain cerebral cortex proteome of rabies-infected cat.comparative proteome analysis using brain cerebral cortex tissues from cats and dogs infected with/without rabies virus were conducted using both two-dimensional gel-electrophoresis (2-de) and 2-d fluorescence difference gel- electrophoresis (2d-dige) methods. the 2-de gel images of all samples revealed >1,000 protein spots in each gel. quantitative intensity analysis revealed the same overall protein pattern in certain regions of the gel, but the rabies-infected brains exhibited more protein sp ...201425427348
safety and immunogenicity of purified chick embryo cell rabies vaccine (vaxirab n) administered intradermally as post exposure prophylaxis.the affordability to rabies vaccine for intramuscular administration in post exposure prophylaxis is a major constraint. therefore, in countries, where there are financial constraints, world health organization recommends intradermal rabies vaccination that reduces the quantity and cost of vaccination. this study was done to evaluate the safety and immunogenicity of indigenously developed rabies vaccine (vaxirab n) in comparison to a who recommended rabies vaccine (rabipur) with demonstrated eff ...201425424951
analysis of adaptive evolution in lyssavirus genomes reveals pervasive diversifying selection during species diversification.lyssavirus is a diverse genus of viruses that infect a variety of mammalian hosts, typically causing encephalitis. the evolution of this lineage, particularly the rabies virus, has been a focus of research because of the extensive occurrence of cross-species transmission, and the distinctive geographical patterns present throughout the diversification of these viruses. although numerous studies have examined pattern-related questions concerning lyssavirus evolution, analyses of the evolutionary ...201425415197
enhancement of immunogenicity and efficacy of a plasmid dna rabies vaccine by nanoformulation with a fourth-generation amine-terminated poly(ether imine) dendrimer.delayed onset of, and low magnitude of, protective immune responses are major drawbacks limiting the practical utility of plasmid vaccination against rabies. in this study we evaluated whether nanoformulation with the novel poly(ether imine) (petim) dendrimer can enhance the immunogenicity and efficacy of a plasmid-based rabies vaccine.201424501540
a recombinant rabies virus encoding two copies of the glycoprotein gene confers protection in dogs against a virulent challenge.the rabies virus (rabv) glycoprotein (g) is the principal antigen responsible for the induction of virus neutralizing antibodies (vna) and is the major modality of protective immunity in animals. a recombinant rabv hep-flury strain was generated by reverse genetics to encode two copies of the g-gene (referred to as hep-dg). the biological properties of hep-dg were compared to those of the parental virus (hep-flury strain). the hep-dg recombinant virus grew 100 times more efficiently in bhk-21 ce ...201424498294
icam-1-based rabies virus vaccine shows increased infection and activation of primary murine b cells in vitro and enhanced antibody titers in-vivo.we have previously shown that live-attenuated rabies virus (rabv)-based vaccines infect and directly activate murine and human primary b cells in-vitro, which we propose can be exploited to help develop a single-dose rabv-based vaccine. here we report on a novel approach to utilize the binding of intracellular adhesion molecule-1 (icam-1) to its binding partner, lymphocyte function-associated antigen-1 (lfa-1), on b cells to enhance b cell activation and rabv-specific antibody responses. we used ...201424489846
mapping sensory circuits by anterograde transsynaptic transfer of recombinant rabies virus.primary sensory neurons convey information from the external world to relay circuits within the cns, but the identity and organization of the neurons that process incoming sensory information remains sketchy. within the cns, viral tracing techniques that rely on retrograde transsynaptic transfer provide a powerful tool for delineating circuit organization. viral tracing of the circuits engaged by primary sensory neurons has, however, been hampered by the absence of a genetically tractable antero ...201424486087
experimental infection of the bat tick carios fonsecai (acari: ixodidae) with the rabies virus.this study assessed the viability of the rabies virus in the argasid tick carios fonsecai following experimental infection.201424474026
medium-term cryopreservation of rabies virus samples.the cryopreservation of rabies virus has been described in detail in the literature. to date, little information is available on the use of cryoprotective agents for cold preservation of this virus, and the available data focus only on short-term virus preservation. in this study, we investigated the medium-term cryopreservation of samples of rabies virus using different cryopreservation protocols.201424474007
limited brain metabolism changes differentiate between the progression and clearance of rabies virus.central nervous system (cns) metabolic profiles were examined from rabies virus (rabv)-infected mice that were either mock-treated or received post-exposure treatment (pet) with a single dose of the live recombinant rabv vaccine trigas. cns tissue harvested from mock-treated mice at middle and late stage infection revealed numerous changes in energy metabolites, neurotransmitters and stress hormones that correlated with replication levels of viral rna. although the large majority of these metabo ...201424763072
molecular characterization of cryptically circulating rabies virus from ferret badgers, taiwan.after the last reported cases of rabies in a human in 1959 and a nonhuman animal in 1961, taiwan was considered free from rabies. however, during 2012-2013, an outbreak occurred among ferret badgers in taiwan. to examine the origin of this virus strain, we sequenced 3 complete genomes and acquired multiple rabies virus (rabv) nucleoprotein and glycoprotein sequences. phylogeographic analyses demonstrated that the rabv affecting the taiwan ferret badgers (rabv-twfb) is a distinct lineage within t ...201424751120
efficient generation of monoclonal antibodies against major structural proteins of rabies virus with suckling mouse brain antigen.the rabies virus is a neurotropic virus that causes fatal disease in humans and animals. however, not all commercial antibodies against rabies virus (rabv) structural proteins are generally available, and production of high-quality monoclonal antibodies (mabs) requires high purification of virus particles and special facilities and is time-consuming. by using rabv-infected suckling mouse brain as antigens in this study, 11 hybridoma cells secreting mabs against rabv were obtained, which showed s ...201424746150
aptamers targeting rabies virus-infected cells inhibit street rabies virus in vivo.rabies is a viral infection of the cns that is almost always fatal once symptoms occur. no effective treatment of the disease is available and novel antiviral strategies are urgently required. street rabies viruses are field isolates known to be highly neurotropic. aptamers are single-stranded oligonucleotides that bind their targets with high affinity and specificity and thus have potential for use in diagnostic and therapeutic applications. in this study, we demonstrate that the aptamers fo24 ...201424735817
[rabies in potos flavus identified in madre de dios, peru].the potos flavus is a nocturnal mammal that lives in neotropical forests from central america to south america. a study of four cases of rabies in potos flavus was conducted; these occurred in april 2012 in the madre de dios region in peru and were collected as part of epidemiological surveillance. the analysis performed in the regional reference laboratory of madre de dios determined the presence of the rabies virus antigen in three of the brain tissue samples. results were verified in the labo ...201424718532
generation of recombinant rabies virus cvs-11 expressing egfp applied to the rapid virus neutralization test.the determination of levels of rabies virus-neutralizing antibody (vna) provides the foundation for the quantitative evaluation of immunity effects. the traditional fluorescent antibody virus neutralization test (favn) using a challenge virus standard (cvs)-11 strain as a detection antigen and staining infected cells with a fluorescein isothiocyanate (fitc)-labeled monoclonal antibody, is expensive and high-quality reagents are often difficult to obtain in developing countries. indeed, it is ess ...201424714411
diagnosis, management and post-mortem findings of a human case of rabies imported into the united kingdom from india: a case report.human rabies infection continues to be a significant public health burden globally, and is occasionally imported to high income settings where the milwaukee protocol for intensive care management has recently been employed, with limited success in improving survival. access to molecular diagnostics, pre- and post-mortem, and documentation of pathophysiological responses while using the milwaukee protocol, can add useful insights for the future of rabies management.201424708671
ginsenoside re as an adjuvant to enhance the immune response to the inactivated rabies virus vaccine in mice.the inactivated rabies virus vaccine (rv) is a relatively expensive vaccine, prone to failure in some cases. ginsenoside re (re) is a saponin isolated from panax ginseng, and has an adjuvant property. here the adjuvant effect of re to improve the immune response to the rv is evaluated in mice. icr mice were immunized with saline, 2.50mg/kg re, 20μl rv, 100μl rv, or 20μl of rv adjuvanted with re (1.25, 2.50 or 5.00mg/kg). different time points after boosting, we measured serum antibodies in blood ...201424680943
a large-scale, rapid public health response to rabies in an organ recipient and the previously undiagnosed organ donor.this article describes and contrasts the public health response to two human rabies cases: one organ recipient diagnosed within days of symptom onset and the transplant donor who was diagnosed 18 months post-symptom onset. in response to an organ-transplant-related rabies case diagnosed in 2013, organ donor and recipient investigations were conducted by multiple public health agencies. persons with potential exposure to infectious patient materials were assessed for rabies virus exposure. an exp ...201424673934
phylodynamics of vampire bat-transmitted rabies in argentina.common vampire bat populations distributed from mexico to argentina are important rabies reservoir hosts in latin america. the aim of this work was to analyse the population structure of the rabies virus (rabv) variants associated with vampire bats in the americas and to study their phylodynamic pattern within argentina. the phylogenetic analysis based on all available vampire bat-related n gene sequences showed both a geographical and a temporal structure. the two largest groups of rabv variant ...201424661865
spatial patterns of neutral and functional genetic variations reveal patterns of local adaptation in raccoon (procyon lotor) populations exposed to raccoon rabies.local adaptation is necessary for population survival and depends on the interplay between responses to selective forces and demographic processes that introduce or retain adaptive and maladaptive attributes. host-parasite systems are dynamic, varying in space and time, where both host and parasites must adapt to their ever-changing environment in order to survive. we investigated patterns of local adaptation in raccoon populations with varying temporal exposure to the raccoon rabies virus (rrv) ...201424655158
[calbindin and parvalbumin distribution in spinal cord of normal and rabies-infected mice].rabies is a fatal infectious disease of the nervous system; however, the knowledge about the pathogenic neural mechanisms in rabies is scarce. in addition, there are few studies of rabies pathology of the spinal cord.201424652212
molecular characterization of three ferret badger (melogale moschata) rabies virus isolates from jiangxi province, china.ferret badger (fb) rabies viruses jx09-17(fb), jx09-18 and jx10-37 were isolated from three different regions in jiangxi province, china, in 2009 and 2010. the complete nucleotide sequence identity between these three isolates was 87-93 %. compared with the other chinese rabies virus isolates and vaccine strains, 101 substitutions (53 in jx10-37, 23 in jx09-17(fb) and 25 in jx09-18) in the five structural proteins were observed, and 47 of these substitutions (27 in jx10-37, 14 in jx09-17(fb) and ...201424643334
rabies virus-like particles expressed in hek293 cells.rabies is an infectious viral disease with a mortality rate close to 100%. currently, there is a need to generate cheaper and more immunogenic vaccines for the effective prevention of rabies, mostly in developing countries. virus-like particles have been widely used in viral vaccine production due to their high immunogenicity and safety during the production process. rabies virus glycoprotein is the major antigen to trigger a protective immune response and the only protein capable of generating ...201424631077
target cells for antibodies detection in rabies vaccine control.rabies causes one of the most lethal zoonotic diseases, with more than 55,000 deaths reported annually. prevention is based on pre-exposure vaccination of individuals at high risk of contracting rabies, and mass vaccination of dog, which are the main vector for transmission to humans. post-exposure prophylaxis includes vaccination and rabies immunoglobulins treatment. the measurement of neutralizing antibodies in sera of vaccinated individuals is a primary concern to determine the efficacy of im ...201424631076
molecular epidemiology of rabies virus in poland.the paper describes a phylogenetic study of 58 polish isolates of rabies virus collected between 1992 and 2010. sequences of the nucleoprotein (n) and glycoprotein (g) genes approximately 600 bp long were compared with reference sequences (genbank) of european rabies viruses from neighbouring countries. the study confirmed a very high level of homology (94.4-100 %) of the polish rabies virus strains irrespective of the date of isolation. two variants of rabies virus: nee (northeastern europe var ...201424627096
a bayesian approach for inferring the dynamics of partially observed endemic infectious diseases from space-time-genetic data.we describe a statistical framework for reconstructing the sequence of transmission events between observed cases of an endemic infectious disease using genetic, temporal and spatial information. previous approaches to reconstructing transmission trees have assumed all infections in the study area originated from a single introduction and that a large fraction of cases were observed. there are as yet no approaches appropriate for endemic situations in which a disease is already well established ...201424619442
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