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updates on rabies virus disease: is evolution toward zombie virus a tangible threat?human rabies disease is caused by rabies lyssavirus, a virus belonging to rhabdoviridae family. the more frequent means of contagion is through bites of infected mammals (especially dogs, but also bats, skunks, foxes, raccoons and wolves) which, lacerating the skin, directly inoculate virus-laden saliva into the underlying tissues. immediately after inoculation, the rabies virus enters neural axons and migrates along peripheral nerves towards the central nervous system, where it preferentially l ...202133682816
human rabies associated with domestic cat exposures in south africa, 1983-2018.no abstract available.202032633988
predicting the presence and titre of rabies virus-neutralizing antibodies from low-volume serum samples in low-containment facilities.serology is a core component of the surveillance and management of viral zoonoses. virus neutralization tests are a gold standard serological diagnostic, but requirements for large volumes of serum and high biosafety containment can limit widespread use. here, focusing on rabies lyssavirus, a globally important zoonosis, we developed a pseudotype micro-neutralization rapid fluorescent focus inhibition test (pmrffit) that overcomes these limitations. specifically, we adapted an existing micro-neu ...202032931658
defining new pathways to manage the ongoing emergence of bat rabies in latin america.rabies transmitted by common vampire bats (desmodus rotundus) has been known since the early 1900s but continues to expand geographically and in the range of species and environments affected. in this review, we present current knowledge of the epidemiology and management of rabies in d. rotundus and argue that it can be reasonably considered an emerging public health threat. we identify knowledge gaps related to the landscape determinants of the bat reservoir, reduction in bites on humans and l ...202032911766
efficacy of ontario rabies vaccine baits (onrab) against rabies infection in raccoons.in the us, rabies lyssavirus (rabv) only circulates in wildlife species and the most significant reservoir from a public and animal health perspective is the raccoon (procyon lotor). management of wildlife rabies relies principally on oral rabies vaccination (orv) strategies using vaccine-laden bait delivery to free-ranging target hosts, in order to reduce the susceptible population to prevent the spread of and eliminate rabv circulation. our objective was to evaluate efficacy of the ontario rab ...201830037482
infection of neuroblastoma cells by rabies virus is modulated by the virus titer.rabies is a lethal viral infection that can affect almost all mammals, including humans. to better understand the replication of rabies lyssavirus, we investigated if the viral load in brains naturally infected with rabies influences viral internalization and viral growth kinetics in neuroblastoma cells, and if the viral load affects mortality in mice after intradermal infection. we noted that high initial viral loads in brains (group ii) were unfavourable for increasing viral titers during seri ...201829122670
development of molecular and cellular tools to decipher the type i ifn pathway of the common vampire bat.though the common vampire bat, desmodus rotundus, is known as the main rabies virus reservoir in latin america, no tools are available to investigate its antiviral innate immune system. to characterize the ifn-i pathway, we established an immortalized cell line from a d. rotundus fetal lung named fludero. then we molecularly characterized some of the toll-like receptors (tlr3, 7, 8 and 9), the three rig-i-like receptor members, as well as ifnα1 and ifnβ. challenging the fludero cell line with po ...201829122634
comparison of a novel human rabies monoclonal antibody to human rabies immunoglobulin for postexposure prophylaxis: a phase 2/3, randomized, single-blind, noninferiority, controlled study.lack of access to rabies immunoglobulin (rig) contributes to high rabies mortality. a recombinant human monoclonal antibody (sii rmab) was tested in a postexposure prophylaxis (pep) regimen in comparison with a human rig (hrig)-containing pep regimen.201829020321
development and evaluation of the rt-pcr kit for the rabies virus diagnosis.to improve the diagnosis, surveillance, and control for the rabies virus, a kit for hybridization-triggered fluorescence detection of rabies virus dna by the rt-pcr technique was developed and evaluated. the analytical sensitivity of the kit was 4*10 ge per ml. high specificity of the kit was shown using representative sampling of viral, bacterial, and human nucleic acids.201829323857
development and evaluation of a rt-qpcr assay for fast and sensitive rabies diagnosis.rabies virus is endemic to russia, among other countries. it is therefore critical to develop a high-quality and high-precision diagnostic procedure for the control and prevention of infection. the main objective of the research presented here was to develop a reliable rt-qpcr assay for rabies diagnostics. for this purpose, a rabv strains from various biological and geographical origins were used. in addition, rabies-positive and rabies-negative samples, as well as nucleic acids from other virus ...201829108902
3d reconstruction and standardization of the rat facial nucleus for precise mapping of vibrissal motor networks.the rodent facial nucleus (fn) comprises motoneurons (mns) that control the facial musculature. in the lateral part of the fn, populations of vibrissal motoneurons (vmns) innervate two groups of muscles that generate movements of the whiskers. vibrissal mns thus represent the terminal point of the neuronal networks that generate rhythmic whisking during exploratory behaviors and that modify whisker movements based on sensory-motor feedback during tactile-based perception. here, we combined retro ...201828958919
production of recombinant rabies virus glycoprotein by insect cells in a single-use fixed-bed bioreactor.a single-use fixed-bed bioreactor (icellis nano) can be used for cultivating non adherent insect cells, which can be then recovered for scaling up or for harvesting a membrane-associated viral glycoprotein with high quality in terms of preserved protein structure and biological function. here, we describe the procedures for establishing genetically modified drosophila melanogaster schneider 2 (s2) cell cultures in the icellis nano bioreactor and for quantifying by elisa the recombinant rabies vi ...201828921430
changes in innervation of lumbar motoneurons and organization of premotor network following training of transected adult rats.rats with complete spinal cord transection (sct) can recover hindlimb locomotor function under strategies combining exercise training and 5-ht agonist treatment. this recovery is expected to result from structural and functional re-organization within the spinal cord below the lesion. to begin to understand the nature of this reorganization, we examined synaptic changes to identified gastrocnemius (gs) or tibialis anterior (ta) motoneurons (mns) in sct rats after a schedule of early exercise tra ...201828917641
re-emergence of rabies virus maintained by canid populations in paraguay.paraguay has registered no human cases of rabies since 2004, and the last case in dogs, reported in 2009, was due to a variant maintained in the common vampire bat "desmodus rotundus". in 2014, a dog was diagnosed as positive for rabies with aggression towards a boy and all required measures of control were successfully adopted. epidemiological investigation revealed that the dog was not vaccinated and had been attacked by a crab-eating fox, "zorro" (cerdocyon thous). the sample was diagnosed by ...201828913904
integrated anatomical and physiological mapping of striatal afferent projections.the dorsomedial striatum, a key site of reward-sensitive motor output, receives extensive afferent input from cortex, thalamus and midbrain. these projections are integrated by striatal microcircuits containing both spiny projection neurons and local circuit interneurons. to explore target-cell specificity of these projections, we compared inputs onto d1-dopamine receptor positive spiny neurons, parvalbumin-positive fast-spiking interneurons and somatostatin-positive low-threshold-spiking intern ...201829359830
defining objective clusters for rabies virus sequences using affinity propagation clustering.rabies is caused by lyssaviruses, and is one of the oldest known zoonoses. in recent years, more than 21,000 nucleotide sequences of rabies viruses (rabv), from the prototype species rabies lyssavirus, have been deposited in public databases. subsequent phylogenetic analyses in combination with metadata suggest geographic distributions of rabv. however, these analyses somewhat experience technical difficulties in defining verifiable criteria for cluster allocations in phylogenetic trees inviting ...201829357361
evaluation of g2 citric acid-based dendrimer as an adjuvant in veterinary rabies vaccine.for induction of an appropriate immune response, especially in the case of an inactivated vaccine, the use of an adjuvant is crucial. in this study, adjuvanticity effect of g2 dendrimer in veterinary rabies vaccine has been investigated. a nonlinear globular g2 dendrimer comprising citric acid and polyethylene glycol 600 (peg-600) was synthesized and the toxicity was studied in vitro on the j774a.1 cell line. the adjuvanticity effect of the dendrimer was then investigated on rabies virus in nmri ...201829328884
an assessment of shedding with the oral rabies virus vaccine strain spbn gasgas in target and non-target species.a safety requirement for live vaccines is investigating possible shedding in recipients since the presence of replication competent vaccine in secretions could result in direct and indirect horizontal transmission. this is especially relevant for oral rabies vaccine baits that are deliberately distributed into the environment. in the current study, survival of an oral rabies virus vaccine, spbn gasgas, was examined in excretions from different target and non-target species; red fox, raccoon dog, ...201829325820
development of a genotype-by-sequencing immunogenetic assay as exemplified by screening for variation in red fox with and without endemic rabies exposure.pathogens are recognized as major drivers of local adaptation in wildlife systems. by determining which gene variants are favored in local interactions among populations with and without disease, spatially explicit adaptive responses to pathogens can be elucidated. much of our current understanding of host responses to disease comes from a small number of genes associated with an immune response. high-throughput sequencing (hts) technologies, such as genotype-by-sequencing (gbs), facilitate expa ...201829321894
parainfluenza virus 5-vectored vaccines against human and animal infectious diseases.parainfluenza virus 5 (piv5), known as canine parainfluenza virus in the veterinary field, is a negative-sense, nonsegmented, single-stranded rna virus belonging to the paramyxoviridae family. parainfluenza virus 5 is an excellent viral vector and has been used as a live vaccine for kennel cough for many years in dogs without any safety concern. it can grow to high titers in many cell types, and its genome is stable even in the presence of foreign gene insertions. so far, piv5 has been used to d ...201829316047
antigenic site changes in the rabies virus glycoprotein dictates functionality and neutralizing capability against divergent lyssaviruses.lyssavirus infection has a near 100 % case fatality rate following the onset of clinical disease, and current rabies vaccines confer protection against all reported phylogroup i lyssaviruses. however, there is little or no protection against more divergent lyssaviruses and so investigation into epitopes within the glycoprotein (g) that dictate a neutralizing response against divergent lyssaviruses is warranted. importantly, the facilities required to work with these pathogens, including wild-typ ...201829300155
initial pen and field assessment of baits to use in oral rabies vaccination of formosan ferret-badgers in response to the re-emergence of rabies in taiwan.taiwan had been considered rabies free since 1961, until a newly established wildlife disease surveillance program identified rabies virus transmission within the formosan ferret-badger (melogale moschata subaurantiaca) in 2013. ferret-badgers occur throughout southern china and southeast asia, but their ecological niche is not well described.201829293591
adjuvant activity of ethanol extract of hippophae rhamnoides leaves with inactivated rabies virus antigen.hippophae rhamnoides l. (elaeagnaceae), commonly known as seabuckthorn (sbt), is known for its medicinal and nutritional properties.201829235395
the impact of host genetic diversity on virus evolution and emergence.accumulating evidence indicates that biodiversity has an important impact on parasite evolution and emergence. the vast majority of studies in this area have only considered the diversity of species within an environment as an overall measure of biodiversity, overlooking the role of genetic diversity within a particular host species. although theoretical models propose that host genetic diversity in part shapes that of the infecting parasite population, and hence modulates the risk of parasite e ...201829207441
addition of c3d-p28 adjuvant to a rabies dna vaccine encoding the g5 linear epitope enhances the humoral immune response and confers protection.rabies dna vaccines based on full-length glycoprotein (g) induce virus neutralizing antibody (vna) responses and protect against the virus challenge. although conformational epitopes of g are the main target of vnas, some studies have shown that a polypeptide linear epitope g5 is also able to induce vnas. however, a g5 dna vaccine has not been explored. while multiple doses of dna vaccines are required in order to confer a protective immune response, this could be overcome by the inclusion of c3 ...201829191739
immunogenic response in obese patients undergoing rabies post-exposure prophylaxis with combined equine rabies immunoglobulin and rabies vaccination.obesity is a risk factor for increased morbidity and mortality associated with many vaccine preventable infectious diseases such as influenza. moreover, higher volume of passive rabies immunoglobulin (rig) due to weight based dosing might suppress vaccine-induced immune responses in obese patients. this study aimed to evaluate the effect of obesity on humoral immune responses to combined equine rig and rabies vaccine treatment among patients with who category iii exposure to a rabies suspected a ...201829191737
vaccination of ferrets for rabies and distemper.companion ferrets need to be vaccinated against 2 viral diseases that cause neurologic illness: canine distemper and rabies. although not common in ferrets, both viruses are fatal in ferrets and rabies virus is also fatal in humans. in this article, we provide a basic review of the 2 diseases, highlighting key neurologic concerns. we also review and update current vaccine concerns from a practitioner's perspective, including available vaccines, vaccine schedule recommendations, vaccine reactions ...201829146026
structure and assembly of the ebola virus nucleocapsid.ebola and marburg viruses are filoviruses: filamentous, enveloped viruses that cause haemorrhagic fever. filoviruses are within the order mononegavirales, which also includes rabies virus, measles virus, and respiratory syncytial virus. mononegaviruses have non-segmented, single-stranded negative-sense rna genomes that are encapsidated by nucleoprotein and other viral proteins to form a helical nucleocapsid. the nucleocapsid acts as a scaffold for virus assembly and as a template for genome tran ...201729144446
an optimized hmgb1 expressed by recombinant rabies virus enhances immunogenicity through activation of dendritic cells in mice.rabies remains an important public health threat, killing approximately 59,000 people worldwide annually, most of which are from the developing countries of africa and asia where dog rabies are endemic. therefore, developing an affordable and efficacious vaccine for dog-mediated rabies control is needful in these countries. our previous studies indicated that over-expression of granulocyte-macrophage colony stimulating factor (gm-csf) or macrophage inflammatory protein-1 (mip-1α or ccl3) by reco ...201729137362
re-evaluating the effect of favipiravir treatment on rabies virus infection.there is no antiviral treatment available once clinical disease following rabies virus infection has initiated. considered a neglected tropical disease, >60,000 human rabies deaths are estimated each year despite the availability of pre- and post-exposure prophylaxis for pre-immunisation or administration following a potential exposure before the onset of clinical disease. such post-exposure treatments include administration of rabies immunoglobulin (rig) and vaccination at a distant site to pri ...201729132993
the lyssavirus host-specificity conundrum-rabies virus-the exception not the rule.lyssaviruses are a diverse range of viruses which all cause the disease rabies. of the 16 recognized species, only rabies viruses (rabv) have multiple host reservoirs. although lyssaviruses are capable of infecting all mammals, onward transmission in a new host population requires adaptation of the virus, in a number of stages with both host and virus factors determining the outcome. due to an absence of recorded non-rabv host shifts, rabv data is extrapolated to draw conclusions for all lyssavi ...201729182939
a phase ii randomized study to determine the safety and immunogenicity of the novel pika rabies vaccine containing the pika adjuvant using an accelerated regimen.human rabies infection continues to be potentially fatal despite the availability of post-exposure prophylaxis with rabies vaccine. the pika rabies vaccine adjuvant is a tlr3 agonist and has been shown to be safe and immunogenic in clinical phase i studies.201729174316
the effect of selected molecules influencing the detrimental host immune response on a course of rabies virus infection in a murine model.rabies is invariably fatal, when post-exposure prophylaxis is administered after the onset of clinical symptoms. in many countries, rabies awareness is very low and the availability of post-exposure prophylaxis, as recommended by who guidelines, is very limited or non-existent, probably as a consequence of high cost. therefore, new concepts for rabies therapy are needed. innate immune mechanisms involving the production of pro-inflammatory cytokines and chemokines, activated after rabies infecti ...201729153584
[expression and purification of rabies virus glycoprotein and analysis of its specific binding capacity to memory b cells].we aimed to express and purify three rabies virus glycoproteins with different tags and sizes. after analyzing their binding function, we wish to obtain a rabies virus glycoprotein with higher affinity and ability to specifically bind memory b cells. experiments were carried out to express full length, as well as the ectodomain rvg by gene engineering method. combined with the antibody of cd19 and cd27, the candidate protein labeling with fluorescence was used to analyze its binding function. fl ...201729202520
[rabies virus induces the formation of stress granules, which are in close proximity to viral factories]. 201729200383
how social structure drives the population dynamics of the common vampire bat (desmodus rotundus, phyllostomidae)?social systems are major drivers of population structure and gene flow, with important effects on dynamics and dispersal of associated populations of parasites. among bats, the common vampire bat (desmodus rotundus) has likely one of the most complex social structure. using autosomal and mitochondrial markers on vampires from mexico, french guiana and north brazil, from both roosting and foraging areas, we observed an isolation by distance at the wider scale and lower but significant differentia ...201729228367
a thermostable messenger rna based vaccine against rabies.although effective rabies virus vaccines have been existing for decades, each year, rabies virus infections still cause around 50.000 fatalities worldwide. most of these cases occur in developing countries, where these vaccines are not available. the reasons for this are the prohibitive high costs of cell culture or egg grown rabies virus vaccines and the lack of a functional cold chain in many regions in which rabies virus is endemic. here, we describe the excellent temperature resistance of a ...201729216187
immunization with recombinant rabies virus expressing interleukin-18 exhibits enhanced immunogenicity and protection in mice.several studies have shown that interleukin-18 (il-18) plays an important role in both innate and adaptive immune responses. in this study, we investigated the pathogenicity and immunogenicity of recombinant rabies virus expressing il-18 (rhep-il18). experimental results showed that institute of cancer research (icr) mice that received a single intramuscular immunization with rhep-il18 elicited the highest titers of serum neutralizing antibodies and the strongest cell-mediated immune responses t ...201729207661
sequencing and sequence analysis of partial nucleoprotein (n) gene and phylogenetic analysis of rabies virus field isolates from gujarat state, india.the present study was undertaken with an aim of characterization of rabies virus (genus lyssavirus of the family rhabdoviridae under the order mononegavirales) by sequencing of partial nucleoprotein (n) gene of rabies virus and phylogenetic analysis to know the genotype and lineage of rabies virus present in gujarat state of india. a total of 32 samples (18 brain samples and 14 saliva samples) were aseptically collected from live and dead animals (viz. dog, buffalo, cow, goat, donkey and hyena) ...201729291220
the path towards effective antivirals against rabies.rabies virus remains an important burden of disease claiming an estimated 60,000 lives each year, mainly children, and having a huge economical and societal cost. post-exposure prophylaxis (pep) is highly effective, however in patients that present with neurological symptoms the case-fatality ratio is extremely high (>99%). during the last decades several attempts to identify potent and effective antivirals were made. only a few of these demonstrated improvement in clinical signs in animal studi ...201729279280
mannitol treatment is not effective in therapy of rabies virus infection in mice.rabies is a deadly viral disease with an extremely high fatality rate in humans. previously, it was suggested that an enhancement of the blood-brain barrier (bbb) permeability, which allows immune cells and/or antibodies to enter the central nervous system (cns) tissue, is critical to clear the infection. in this study, we utilised mannitol to increase bbb permeability in mice infected with highly pathogenic silver-haired bat rabies virus (shbrv). we found that intraperitoneal injection of manni ...201729274698
landscape attributes governing local transmission of an endemic zoonosis: rabies virus in domestic dogs.landscape heterogeneity plays an important role in disease spread and persistence but quantifying landscape influences and their scale-dependence is challenging. studies have focused on how environmental features or global transport networks influence pathogen invasion and spread, but their influence on local transmission dynamics that underpin the persistence of endemic diseases remains unexplored. bayesian phylogeographic frameworks that incorporate spatial heterogeneities are promising tools ...201729274171
development and evaluation of an anti-rabies virus phosphoprotein-specific monoclonal antibody for detection of rabies neutralizing antibodies using rffit.rabies is a major public health problem with a fatality rate close to 100%; however, complete prevention can be achieved through pre- or post-exposure prophylaxis. the rapid fluorescent focus inhibition test (rffit) is one of the recommended testing methods to determine the production of neutralizing antibodies after vaccination. here, we report the development of a new monoclonal antibody (mab) designed to react specifically with rabies virus (rabv) phosphoprotein (p protein), and the evaluatio ...201729267277
vaccination of dogs in an african city interrupts rabies transmission and reduces human exposure.despite the existence of effective rabies vaccines for dogs, dog-transmitted human rabies persists and has reemerged in africa. two consecutive dog vaccination campaigns took place in chad in 2012 and 2013 (coverage of 71% in both years) in the capital city of n'djaména, as previously published. we developed a deterministic model of dog-human rabies transmission fitted to weekly incidence data of rabid dogs and exposed human cases in n'djaména. our analysis showed that the effective reproductive ...201729263230
syn023, a novel humanized monoclonal antibody cocktail, for post-exposure prophylaxis of rabies.rabies is a neglected zoonotic disease that is preventable in humans by appropriate post-exposure prophylaxis (pep). however, current pep relies on polyclonal immune globulin products purified from pooled human (hrig) or equine (erig) plasma that are either in chronic shortage or in association with safety concerns. here, we present the development of an antibody cocktail, syn023, made of two novel monoclonal antibodies (mab) ctb011 and ctb012 that could serve as safer and more cost-effective al ...201729261658
genetic analysis of a rabies virus host shift event reveals within-host viral dynamics in a new host.host shift events play an important role in epizootics as adaptation to new hosts can profoundly affect the spread of the disease and the measures needed to control it. during the late 1990s, an epizootic in turkey resulted in a sustained maintenance of rabies virus (rabv) within the fox population. we used bayesian inferences to investigate whole genome sequences from fox and dog brain tissues from turkey to demonstrate that the epizootic occurred in 1997 (±1 year). furthermore, these data indi ...201729255631
seroprevalence of rabies virus antibodies in bats from high risk areas in brazilian amazonia between 2013 and 2015.the outbreaks of human rabies that occurred between 2004 and 2005 in the brazilian amazon highlight the importance of bats in the transmission of this zoonosis. ten years after, this region is still considered to be a risk area.201729237041
rabies: a novel clinical presentation.rabies is a fatal disease. saliva of a rabid dog is a rich source of rabies virus. we report a patient who suffered of rabies, who was infected by abrasion caused by the nails of a rabid dog. dogs often lick their nails and thereby transfer the rabies virus-contaminated saliva to their claws. despite treatment in our intensive care unit and application of various pharmacological antidotes, we were unable to prevent the fatal outcome.201729307972
multizonal cerebellar influence over sensorimotor areas of the rat cerebral cortex.the cerebral cortex requires cerebellar input for optimizing sensorimotor processing. however, how the sensorimotor cortex uses cerebellar information is far from understood. one critical and unanswered question is how cerebellar functional entities (zones or modules) are connected to distinct parts of the sensorimotor cortices. here, we utilized retrograde transneuronal infection of rabies virus (rabv) to study the organization of connections from the cerebellar cortex to m1, m2, and s1 of the ...201729300895
pathological findings in the red fox (vulpes vulpes), stone marten (martes foina) and raccoon dog (nyctereutes procyonoides), with special emphasis on infectious and zoonotic agents in northern germany.anthropogenic landscape changes contributed to the reduction of availability of habitats to wild animals. hence, the presence of wild terrestrial carnivores in urban and peri-urban sites has increased considerably over the years implying an increased risk of interspecies spillover of infectious diseases and the transmission of zoonoses. the present study provides a detailed characterisation of the health status of the red fox (vulpes vulpes), stone marten (martes foina) and raccoon dog (nyctereu ...201728399176
serology and protein electrophoresis for evidence of exposure to 12 mink pathogens in free-ranging american mink (neovison vison) in argentina.basic pathologic characteristics for farmed minks were previously reported worldwide. however, its status in the wild has not been studied in detail.201728635524
rabies virus exposure of brazilian free-ranging wildlife from municipalities without clinical cases in humans or in terrestrial wildlife.rabies is a zoonosis that causes thousands of animal and human deaths worldwide. serological studies provide information concerning rabies virus circulation among animals and humans. we evaluated the circulation of the rabies virus in wildlife in nine municipalities of são paulo state, brazil. we took blood samples from 27 terrestrial animals of nine different mammalian species in locations without cases of rabies in human and wild terrestrial mammals. sera were tested with the use of the rapid ...201728406757
experimental infection of artibeus intermedius with a vampire bat rabies virus.experimental infection of artibeus intermedius, the great fruit-eating bat, was performed with vampire bat rabies isolates. bats (n=35) were captured in the wild and quarantined prior to experimental infection. no rabies antibodies were detected by rapid fluorescent focus inhibition test (rffit) prior to infection. three doses of rabies virus (rv) and three different routes of infection were used. one out of 35 bats died without showing any clinical signs at day 14 and was positive for rabies. n ...201728673461
natural exposure of bats in grenada to rabies virus.introduction: grenada is a rabies endemic country, where terrestrial rabies is maintained in the small indian mongoose (herpestes auropunctatus). the role of bats in the epidemiology of rabies in grenada is unknown. a 1974 report described one rabies virus positive jamaican fruit bat (artibeus jamaicensis), and a high seroprevalence in this species. in the current study, the natural exposure to rabies virus in grenadian bats was re-evaluated. it is postulated that bats serve as a natural rabies ...201728804595
ultrastructure and morphometric features of epididymal epithelium in desmodus rotundus.the blood-feeding behavior of desmodus rotundus made this bat a potential vector of rabies virus and a public health issue. consequently, the better understanding of its reproductive biology becomes valuable for the development of methods to control its population. in this study, we described morphological aspects of epithelial cells in d. rotundus' epididymis using light and transmission electron microscopy methods. the duct compartment was the main component of initial segment (83%), caput (90 ...201728869875
whole genome sequence phylogenetic analysis of four mexican rabies viruses isolated from cattle.phylogenetic analysis of the rabies virus in molecular epidemiology has been traditionally performed on partial sequences of the genome, such as the n, g, and p genes; however, that approach raises concerns about the discriminatory power compared to whole genome sequencing. in this study we characterized four strains of the rabies virus isolated from cattle in querétaro, mexico by comparing the whole genome sequence to that of strains from the american, european and asian continents. four cattle ...201728818750
genetic demography at the leading edge of the distribution of a rabies virus vector.the common vampire bat, desmodus rotundus, ranges from south america into northern mexico in north america. this sanguivorous species of bat feeds primarily on medium to large-sized mammals and is known to rely on livestock as primary prey. each year, there are hotspot areas of d. rotundus-specific rabies virus outbreaks that lead to the deaths of livestock and economic losses. based on incidental captures in our study area, which is an area of high cattle mortality from d. rotundus transmitted ...201728770072
rabies virus in bats, state of pará, brazil, 2005-2011.rabies is an acute, progressive zoonotic viral infection that in general produces a fatal outcome. this disease is responsible for deaths in humans and animals worldwide and, because it can affect all mammals, is considered one of the most important viral infections for public health. this study aimed to determine the prevalence of rabies in bats of different species found in municipalities of the state of pará from 2005 to 2011. the rabies virus was detected in 12 (0.39%) bats in a total of 310 ...201728678651
predictors and immunological correlates of sublethal mercury exposure in vampire bats.mercury (hg) is a pervasive heavy metal that often enters the environment from anthropogenic sources such as gold mining and agriculture. chronic exposure to hg can impair immune function, reducing the ability of animals to resist or recover from infections. how hg influences immunity and susceptibility remains unknown for bats, which appear immunologically distinct from other mammals and are reservoir hosts of many pathogens of importance to human and animal health. we here quantify total hg (t ...201728484633
the phylogeography of myotis bat-associated rabies viruses across canada.as rabies in carnivores is increasingly controlled throughout much of the americas, bats are emerging as a significant source of rabies virus infection of humans and domestic animals. knowledge of the bat species that maintain rabies is a crucial first step in reducing this public health problem. in north america, several bat species are known to be rabies virus reservoirs but the role of bats of the myotis genus has been unclear due to the scarcity of laboratory confirmed cases and the challeng ...201728542160
characterization of akabane virus from domestic bamboo rat, southern china.to identify the causative agents in 3 large-scale outbreaks of encephalitis and death among farmed bamboo rats (rhizomys pruinosus). the routine bacterial culture and identification were performed. there were no significant pathogenic bacteria isolated from the brain, heart, liver, spleen, lung, or kidney of diseased bamboo rats. using pcr-based methods, we excluded the following as causative agent: pox virus, herpesvirus, adenovirus, lymphocytic choriomeningitis virus, rabies virus, and sendai ...201728757035
neuropathogenesis by chandipura virus: an acute encephalitis syndrome in india.chandipura virus (chpv) has been contributing to the rising number of premature deaths due to acute encephalitis syndrome for over a decade in india. chpv belongs to the family rhabdoviridae. neuropathogenesis of chpv has been well established but the exact route of entry into the central nervous system (cns) and the triggering factor for neuronal death are still unknown. rabies virus and vesicular stomatitis virus, which are related closely to chpv, enter the cns retrogradely from peripheral or ...201728731002
genetically modified rabies virus-vectored ebola virus disease vaccines are safe and induce efficacious immune responses in mice and dogs.ebola viruses (ebovs) are zoonotic pathogens that cause ebov disease (evd) with high case fatality in humans. currently, evd vaccines are still under development in several countries. here, we generated two recombinant rabies viruses (rabvs), rerag333e/zgp and rerag333e/sgp, expressing the zaire ebov glycoprotein (zgp) or sudan ebov glycoprotein (sgp) gene based on a modified era vaccine strain (rerag333e) vector platform. the recombinant rabvs retained growth properties similar to those of the ...201728822816
evolution and antiviral specificities of interferon-induced mx proteins of bats against ebola, influenza, and other rna viruses.bats serve as a reservoir for various, often zoonotic viruses, including significant human pathogens such as ebola and influenza viruses. however, for unknown reasons, viral infections rarely cause clinical symptoms in bats. a tight control of viral replication by the host innate immune defense might contribute to this phenomenon. transcriptomic studies revealed the presence of the interferon-induced antiviral myxovirus resistance (mx) proteins in bats, but detailed functional aspects have not b ...201728490593
cloning and expression of fragment of the rabies virus nucleoprotein gene in escherichia coli and evaluation of antigenicity of the expression product.rabies virus nucleoprotein (n protein) encapsidates genomic rna of the virus and forms the viral ribonucleoprotein complex. these n proteins represent highly organized structures which activate proliferation of b cells and production antibodies against the n protein. in addition to the b cell, the rabies virus n protein has been shown to induce potent t helper cell responses resulting in a long-lasting and strong humoral immune response. rabies virus n protein is a molecular target of choice for ...201728588631
flagellin fljb as an adjuvant to the recombinant adenovirus rabies glycoprotein vaccine increases immune responses against rabies in mice.rabies virus (rabv) causes an acute progressive viral encephalitis. although currently licensed vaccines have an excellent safety and efficacy record, the development of a safer and more cost-effective vaccine is still being sought. an e1-deleted, replication-defective human adenovirus type 5 (had5) vector expressing rabv glycoprotein (had5-g) is thought to be a promising candidate vaccine for immune prophylaxis against rabies. salmonella enterica serovar typhimurium (s. typhimurium) flagellin i ...201728550434
pseudotyped lentiviral vectors for retrograde gene delivery into target brain regions.gene transfer through retrograde axonal transport of viral vectors offers a substantial advantage for analyzing roles of specific neuronal pathways or cell types forming complex neural networks. this genetic approach may also be useful in gene therapy trials by enabling delivery of transgenes into a target brain region distant from the injection site of the vectors. pseudotyping of a lentiviral vector based on human immunodeficiency virus type 1 (hiv-1) with various fusion envelope glycoproteins ...201728824385
large protein as a potential target for use in rabies diagnostics.rabies is a zoonotic viral disease that remains a serious threat to public health worldwide. the rabies lyssavirus (rabv) genome encodes five structural proteins, multifunctional and significant for pathogenicity. the large protein (l) presents well-conserved genomic regions, which may be a good alternative to generate informative datasets for development of new methods for rabies diagnosis. this paper describes the development of a technique for the identification of l protein in several rabv s ...201728854792
resurgence of rabies in hungary during 2013-2014: an attempt to track the origin of identified strains.in 2013-2014, accumulation of rabies episodes raised concerns regarding ongoing elimination programme in hungary. nearly four dozen cases were identified over a 13-month period in the central region of the country far behind the immunization zones. although the outbreak was successfully controlled, the origin of disease remained unknown. in this study, we sequenced the partial n and g genes from 47 hungarian rabies virus (rv) strains isolated from the 2013-2014 outbreak. sequencing and phylogene ...201728497505
protective immune response of oral rabies vaccine in stray dogs, corsacs and steppe wolves after a single immunization.in this study the safety and protective immunity of an oral rabies vaccine, based on the live, modified rabies virus strain vrc-rz2, was examined in stray dogs (canis sp.), corsacs (vulpes corsac) and steppe wolves (canis lupus campestris). in the safety group (dogs, n=6; corsacs, n=3; wolves, n=3) which was vaccinated with a 10-times field dose/animal, no animals showed any signs of disease or changes in behavior or appetite during the period of clinical observation, similar to the animals in t ...201728766059
a rabies virus vampire bat variant shows increased neuroinvasiveness in mice when compared to a carnivore variant.rabies is one of the most important zoonotic diseases and is caused by several rabies virus (rabv) variants. these variants can exhibit differences in neurovirulence, and few studies have attempted to evaluate the neuroinvasiveness of variants derived from vampire bats and wild carnivores. the aim of this study was to evaluate the neuropathogenesis of infection with two brazilian rabv street variants (variant 3 and crab-eating fox) in mice. balb/c mice were inoculated with rabv through the footp ...201728831620
comparison of g protein sequences of south african street rabies viruses showing distinct progression of the disease in a mouse model of experimental rabies.rabies is a fatal zoonotic disease and infections generally lead to a fatal encephalomyelitis in both humans and animals. in south africa, domestic (dogs) and the wildlife (yellow mongoose) host species maintain the canid and mongoose rabies variants respectively. in this study, pathogenicity differences of south african canid and mongoose rabies viruses were investigated in a murine model, by assessing the progression of clinical signs and survivorship. comparison of glycoprotein gene sequences ...201728627433
oral vaccination of wildlife against rabies: differences among host species in vaccine uptake efficiency.oral vaccination using attenuated and recombinant rabies vaccines has been proven a powerful tool to combat rabies in wildlife. however, clear differences have been observed in vaccine titers needed to induce a protective immune response against rabies after oral vaccination in different reservoir species. the mechanisms contributing to the observed resistance against oral rabies vaccination in some species are not completely understood. hence, the immunogenicity of the vaccine virus strain, spb ...201728641888
indigenous wildlife rabies in taiwan: ferret badgers, a long term terrestrial reservoir.the emerging disease of rabies was confirmed in taiwan ferret badgers (fbs) and reported to the world organization for animal health (oie) on july 17, 2013. the spread of wildlife rabies can be related to neighborhood countries in asia. the phylogenetic analysis was conducted by maximum likelihood (ml) methods and the bayesian coalescent approach based on the glycoprotein (g) and nucleoprotein (n) genes. the phylogeographic and spatial temporal dynamics of viral transmission were determined by u ...201728497055
processes underlying rabies virus incursions across us-canada border as revealed by whole-genome phylogeography.disease control programs aim to constrain and reduce the spread of infection. human disease interventions such as wildlife vaccination play a major role in determining the limits of a pathogen's spatial distribution. over the past few decades, a raccoon-specific variant of rabies virus (rrv) has invaded large areas of eastern north america. although expansion into canada has been largely prevented through vaccination along the us border, several outbreaks have occurred in canada. applying phylog ...201728820138
using viral gene sequences to compare and explain the heterogeneous spatial dynamics of virus epidemics.rabies is an important zoonotic disease distributed worldwide. a key question in rabies epidemiology is the identification of factors that impact virus dispersion. here we apply new analytical methods, based on phylogeographic reconstructions of viral lineage movement, to undertake a comparative evolutionary-epidemiological study of the spatial dynamics of rabies virus (rabv) epidemics in different hosts and habitats. we have compiled rabv data sets from skunk, raccoon, bat and domestic dog popu ...201728651357
rabies - epidemiology, pathogenesis, public health concerns and advances in diagnosis and control: a comprehensive review.rabies is a zoonotic, fatal and progressive neurological infection caused by rabies virus of the genus lyssavirus and family rhabdoviridae. it affects all warm-blooded animals and the disease is prevalent throughout the world and endemic in many countries except in islands like australia and antarctica. over 60,000 peoples die every year due to rabies, while approximately 15 million people receive rabies post-exposure prophylaxis (pep) annually. bite of rabid animals and saliva of infected host ...201728643547
geographical clusters and predictors of rabies in three southeastern states.the rabies virus causes progressive encephalomyelitis that is fatal in nearly 100% of untreated cases. in the united states, wildlife act as the primary reservoir for rabies; prevention, surveillance, and control costs remain high. the purpose of this study is to understand the current distribution of wildlife rabies in three southeastern states, with particular focus on raccoons as the primary eastern reservoir, as well as identify demographic and geographic factors which may affect the risk of ...201728418772
assessment of the immunogenicity of rabies vaccine preserved by vaporization and delivered to the duodenal mucosa of gray foxes (urocyon cinereoargenteus).objective to assess the immunogenicity of thermostable live-attenuated rabies virus (rabv) preserved by vaporization (pbv) and delivered to the duodenal mucosa of a wildlife species targeted for an oral vaccination program. animals 8 gray foxes (urocyon cinereoargenteus). procedures endoscopy was used to place rabv pbv (n = 3 foxes), alginate-encapsulated rabv pbv (3 foxes), or nonpreserved rabv (2 foxes) vaccine into the duodenum of foxes. blood samples were collected weekly to monitor the immu ...201728541146
whole-brain mapping of the inputs and outputs of the medial part of the olfactory tubercle.the medial part of the olfactory tubercle (ot) is a brain structure located at the interface of the reward and olfactory system. it is closely related to pheromone-rewards, natural reinforcement, addiction and many other behaviors. however, the structure of the anatomic circuitry of the medial part of the ot is still unclear. in the present study, the medial part of the ot was found to be highly connected with a wide range of brain areas with the help of the pseudorabies virus tracing tool. in o ...201728804450
longitudinal survey of two serotine bat (eptesicus serotinus) maternity colonies exposed to eblv-1 (european bat lyssavirus type 1): assessment of survival and serological status variations using capture-recapture models.this study describes two longitudinal serological surveys of european bat lyssavirus type 1 (eblv-1) antibodies in serotine bat (eptesicus serotinus) maternity colonies located in the north-east of france. this species is currently considered as the main eblv-1 reservoir. multievent capture-recapture models were used to determine the factors influencing bat rabies transmission as this method accounts for imperfect detection and uncertainty in disease states. considering the period of study, anal ...201729149215
efficacy of rabies vaccines in dogs and cats and protection in a mouse model against european bat lyssavirus type 2.rabies is preventable by pre- and/or post-exposure prophylaxis consisting of series of rabies vaccinations and in some cases the use of immunoglobulins. the success of vaccination can be estimated either by measuring virus neutralising antibodies or by challenge experiment. vaccines based on rabies virus offer cross-protection against other lyssaviruses closely related to rabies virus. the aim was to assess the success of rabies vaccination measured by the antibody response in dogs (n = 10,071) ...201728969696
rabies screen reveals gpe control of cocaine-triggered plasticity.identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. cocaine increased rabies-labelled inputs from the ...201728902833
a novel approach to a rabies vaccine based on a recombinant single-cycle flavivirus vector.the replivax® vaccine (rv) platform is based on flavivirus genomes that are rationally attenuated by deletion. these single-cycle rv vaccine candidates targeting flavivirus pathogens have been demonstrated to be safe, highly immunogenic, and efficacious in animal models, including non-human primates. here we show utility of the technology for delivery of a non-flavivirus immunogen by engineering several west nile-based rv vectors to express full-length rabies virus g protein. the rabies virus g ...201728899628
immunogenicity of orfv-based vectors expressing the rabies virus glycoprotein in livestock species.the parapoxvirus orf virus (orfv) encodes several immunomodulatory proteins (imps) that modulate host-innate and pro-inflammatory responses and has been proposed as a vaccine delivery vector for use in animal species. here we describe the construction and characterization of two recombinant orfv vectors expressing the rabies virus (rabv) glycoprotein (g). the rabv-g gene was inserted in the orfv024 or orfv121 gene loci, which encode for imps that are unique to parapoxviruses and inhibit activati ...201728898730
a self-killing rabies virus that leaves a trace on the dna.although modified rabies viruses have emerged as a powerful tool for tracing the inputs to genetically defined populations of neurons, the toxicity of the virus has limited its utility. a recent study employed a self-inactivating rabies (sir) virus that enables recording or manipulation of targeted neurons for months.201728890212
generation of a novel live rabies vaccine strain with a high level of safety by introducing attenuating mutations in the nucleoprotein and glycoprotein.the current live rabies vaccine sag2 is attenuated by only one mutation (arg-to-glu) at position 333 in the glycoprotein (g333). this fact generates a potential risk of the emergence of a pathogenic revertant by a back mutation at this position during viral propagation in the body. to circumvent this risk, it is desirable to generate a live vaccine strain highly and stably attenuated by multiple mutations. however, the information on attenuating mutations other than that at g333 is very limited. ...201728882441
vaccines against botulism.botulinum neurotoxins (bont) cause the flaccid paralysis of botulism by inhibiting the release of acetylcholine from motor neurons. there are seven serotypes of bont (a-g), with limited therapies, and no fda approved vaccine for botulism. an investigational formalin-inactivated penta-serotype-bont/a-e toxoid vaccine was used to vaccinate people who are at high risk of contracting botulism. however, this formalin-inactivated penta-serotype-bont/a-e toxoid vaccine was losing potency and was discon ...201728869493
a data platform to improve rabies prevention, sri lanka.in sri lanka, rabies prevention initiatives are hindered by fragmented and delayed information-sharing that limits clinicians' ability to follow patients and impedes public health surveillance.201728867845
recombinant rabies virus expressing il-15 enhances immunogenicity through promoting the activation of dendritic cells in mice.rabies remains a public health threat that kills approximately 59,000 people worldwide each year, most of which are from the developing countries of africa and asia where dog rabies are endemic. therefore, developing an affordable and efficacious vaccine is crucial for rabies control in these countries. interleukin (il)-15, an immunoregulatory cytokine, is a pluripotent molecule with therapeutic potential, which targets many cell types and links the innate and adaptive immune system. in this stu ...201728861771
glycoprotein-g-gene-based molecular and phylogenetic analysis of rabies viruses associated with a large outbreak of bovine rabies in southern brazil.a large outbreak of hematophagous-bat-associated bovine rabies has been occurring in rio grande do sul (rs), the southernmost brazilian state, since 2011, with official estimates exceeding 50,000 cattle deaths. the present article describes a genetic characterization of rabies virus (rabv) recovered from 59 affected cattle and two sheep, from 56 herds in 16 municipalities (2012-2016). molecular analysis was performed using the nucleotide (nt) and predicted amino acid (aa) sequences of rabv glyco ...201728856449
incidence of human rabies and characterization of rabies virus nucleoprotein gene in dogs in fujian province, southeast china, 2002-2012.rabies is a global fatal infectious viral disease that is characterized by a high mortality after onset of clinical symptoms. recently, there has been an increase in the incidence of rabies in china. the aim of this study was to investigate the incidence of human rabies and characterize the rabies virus nucleoprotein gene in dogs sampled from fujian province, southeast china from 2002 to 2012.201728854892
plant-made vaccines and reagents for the one health initiative.the one health initiative is increasingly becoming a prominent discussion topic in animal and human health, with its focus on prevention of spread of zoonotic diseases, both in animals, and from animals to humans. an important part of one health is that diagnostics and vaccines for diseases may be the same thing - and be used for both humans and animals. one potential problem standing in the way of wider adoption of one health principles, though, is that use of conventional cell fermentation sys ...201728846485
comparison of a micro-neutralization test with the rapid fluorescent focus inhibition test for measuring rabies virus neutralizing antibodies.the rapid fluorescent focus inhibition test (rffit) is routinely used in the united states to measure rabies virus neutralizing antibodies (rvna). rffit has a long history of reproducible and reliable results. the test has been modified over the years to use smaller volumes of reagents and samples, but requires a 50 μl minimum volume of test serum. to conduct pathogenesis studies, small laboratory animals such as mice are regularly tested for rvna, but the minimum volume for a standard rffit may ...201728845465
rabies virus transmission in solid organ transplantation, china, 2015-2016.we report rabies virus transmission among solid organ transplantation recipients in changsha, china, in 2016. two recipients were confirmed to have rabies and died. our findings suggest that more attention should be paid to the possibility of rabies virus transmission through organ transplantation for clinical and public health reasons.201728820377
molecular characterization of atypical antigenic variants of canine rabies virus reveals its reintroduction by wildlife vectors in southeastern mexico.rabies is an infectious viral disease that is practically always fatal following the onset of clinical signs. in mexico, the last case of human rabies transmitted by dogs was reported in 2006 and canine rabies has declined significantly due to vaccination campaigns implemented in the country. here we report on the molecular characterization of six rabies virus strains found in yucatan and chiapas, remarkably, four of them showed an atypical reaction pattern when antigenic characterization with a ...201728819692
codon usage bias in the n gene of rabies virus.since its emergence, rabies virus (rabv) has been a major worldwide concern especially in developing countries. the nucleoprotein (n) of rabv is highly conserved and key for genetic typing, thus a better understanding of the n gene evolutionary trajectory can assist the development of control measures. we found that the n gene of rabv has a low codon usage bias with a mean effective number of codons (enc) value of 56.33 influenced by both mutation pressure and natural selection. however, neutral ...201728818621
enhancing immune responses to cancer vaccines using multi-site injections.for a vaccine to be effective it must induce a sufficiently robust and specific immune response. multi-site injection protocols can increase the titers of rabies virus-neutralizing antibodies. hypothetically, spreading a vaccine dose across multiple lymphatic drainage regions could also potentiate t cell responses. we used a replication-deficient adenovirus serotype 5-vectored cancer vaccine targeting the melanoma-associated antigen dopachrome tautomerase. clinically, high numbers of tumor-infil ...201728814733
a time-resolved fluoroimmunoassay to assay the rabies virus glycoprotein: application for estimation of human rabies vaccine potency.replacement of the in vivo rabies vaccine potency test (nih test) by in vitro methods had been discussed by several researcher including who expert working groups. in this paper, a time-resolved fluoroimmunoassay (trfia) for the assay of rabies virus glycoprotein in rabies vaccine was first established to estimate the rabies vaccine potency by using specific monoclonal antibody that only recognized the native, trimeric and immunogenic form of rabies virus glycoprotein. potency of the rabies viru ...201728779162
a genetically modified rabies vaccine (erags) induces protective immunity in dogs and cattle.the current live attenuated rabies vaccine must be replaced with a safer vaccine based on the erags strain to prevent rabies in south korea. we evaluated the safety and immunogenicity of a new strain in dogs and cattle.201728775977
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