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[c-terminal lysosome targeting domain of cd63 modifies cellular localization of rabies virus glycoprotein].the glycoprotein of rabies virus is the central antigen elicited the immune response to infection; therefore, the majority of developing anti-rabies vaccines are based on this protein. in order to increase the efficacy of dna immunogen encoding rabies virus glycoprotein, the construction of chimeric protein with the cd63 domain has been proposed. the cd63 is a transmembrane protein localized on the cell surface and in lysosomes. the lysosome targeting motif gyevm is located at its c-terminus. we ...201728707662
immunological aspects of rabies: a literature review.rabies is a lethal disease caused by the neurotropic virus rabies virus (rabv), and it remains an important public health problem globally. it is known that the host immune response is important for control of viral infection and promoting viral clearance. in this context, it is well documented that, in addition to rabv neutralizing antibody, interferons and cell-mediated immunity also have an important role in preventing the establishment of disease. on the other hand, rabv suppresses host immu ...201728726129
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
safety and immunogenicity of a mrna rabies vaccine in healthy adults: an open-label, non-randomised, prospective, first-in-human phase 1 clinical trial.vaccines based on mrna coding for antigens have been shown to be safe and immunogenic in preclinical models. we aimed to report results of the first-in-human proof-of-concept clinical trial in healthy adults of a prophylactic mrna-based vaccine encoding rabies virus glycoprotein (cv7201).201728754494
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
hippocampal tert regulates spatial memory formation through modulation of neural development.the molecular mechanism of memory formation remains a mystery. here, we show that tert, the catalytic subunit of telomerase, gene knockout (tert-/-) causes extremely poor ability in spatial memory formation. knockdown of tert in the dentate gyrus of adult hippocampus impairs spatial memory processes, while overexpression facilitates it. we find that tert plays a critical role in neural development including dendritic development and neuritogenesis of hippocampal newborn neurons. a monosynaptic p ...201728757168
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
molecular function analysis of rabies virus rna polymerase l protein by using an l gene-deficient virus.while the rna-dependent rna polymerase l protein of rabies virus (rabv), a member of the genus lyssavirus of the family rhabdoviridae, has potential to be a therapeutic target for rabies, the molecular functions of this protein have remained largely unknown. in this study, to obtain a novel experimental tool for molecular function analysis of the rabv l protein, we established by using a reverse genetics approach an l gene-deficient rabv (nishi-δl/nluc), which infects, propagates, and correspond ...201728768857
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
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
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
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
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
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
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
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
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
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
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
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
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
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 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
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
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
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
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
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
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
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
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
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
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
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 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
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
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
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
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
phosphoprotein gene contributes to the enhanced apoptosis induced by wild-type rabies virus gd-sh-01 in vitro.previous research demonstrated that the matrix protein (m) and glycoprotein (g) of attenuated rabies virus (rabv) strains are involved in the induction of host cell apoptosis. in this work, we show that wild-type (wt) rabv gd-sh-01 induces significantly greater apoptosis than the attenuated strain hep-flury. in order to identify the gene(s) accounting for this phenotype, five recombinant rabvs (rrabvs) were constructed by replacing each single gene of hep-flury with the corresponding gene of gd- ...201728928726
single visit rabies pre-exposure priming induces a robust anamnestic antibody response after simulated post-exposure vaccination: results of a dose-finding study.the current standard 3-dose intramuscular rabies prep schedule suffers from a number of disadvantages that severely limit accessibility and availability. the cost of is often prohibitive, it requires 3 visits to the clinic, and there are regular vaccine shortages.201728931127
development of molecular confirmation tools for swift and easy rabies diagnostics.as rabies still represents a major public threat with tens of thousands of deaths per year, particularly in developing countries, adequate surveillance based on rapid and reliable rabies diagnosis for both humans and animals is essential. rabies diagnosis relies on highly sensitive and specific laboratory tests for detection of viral antigens. among those tests, at present the immunofluorescence antibody test is the "gold standard test" for rabies diagnosis, followed by virus isolation in either ...201728938887
oral vaccination of wildlife using a vaccinia-rabies-glycoprotein recombinant virus vaccine (raboral v-rg®): a global review.raboral v-rg® is an oral rabies vaccine bait that contains an attenuated ("modified-live") recombinant vaccinia virus vector vaccine expressing the rabies virus glycoprotein gene (v-rg). approximately 250 million doses have been distributed globally since 1987 without any reports of adverse reactions in wildlife or domestic animals since the first licensed recombinant oral rabies vaccine (orv) was released into the environment to immunize wildlife populations against rabies. v-rg is genetically ...201728938920
inhibition of mek-erk1/2-map kinase signalling pathway reduces rabies virus induced pathologies in mouse model.the extracellular signal-regulated kinase (erk) pathway has been shown to regulate pathogenesis of many viral infections, but its role during rabies virus (rv) infection in vivo is not clear. in the present study, we investigated the potential role of mek-erk1/2 signalling pathway in the pathogenesis of rabies in mouse model and its regulatory effects on pro-inflammatory cytokines and other mediators of immunity, and kinetics of immune cells. mice were infected with 25 ld50 of challenge virus st ...201728939254
identification of two classes of somatosensory neurons that display resistance to retrograde infection by rabies virus.glycoprotein-deleted rabies virus-mediated monosynaptic tracing has become a standard method for neuronal circuit mapping, and is applied to virtually all parts of the rodent nervous system, including the spinal cord and primary sensory neurons. here we identified two classes of unmyelinated sensory neurons (nonpeptidergic and c-fiber low-threshold mechanoreceptor neurons) resistant to direct and trans-synaptic infection from the spinal cord with rabies viruses that carry glycoproteins in their ...201728951448
enhanced immune response to rabies viruses by the use of a liposome adjuvant in vaccines.essen regimen, the thai red cross two-site id regimen, zagreb schedule, and the eight-site id regimen are the standard rabies vaccines recommended by the world health organization (who). in this study, a liposomal rabies vaccine (liporv) was developed, which was found to facilitate the production of rabies virus neutralizing antibody (rvna) in balb/c mice. liposome solution was prepared with hydrogenated soya phosphatide and cholesterol. liporv composed of liposome solution and inactivated rabie ...201728953450
differentiated human sh-sy5y cells provide a reductionist model of herpes simplex virus 1 neurotropism.neuron-virus interactions that occur during herpes simplex virus (hsv) infection are not fully understood. neurons are the site of lifelong latency and are a crucial target for long-term suppressive therapy or viral clearance. a reproducible neuronal model of human origin would facilitate studies of hsv and other neurotropic viruses. current neuronal models in the herpesvirus field vary widely and have caveats, including incomplete differentiation, nonhuman origins, or the use of dividing cells ...201728956768
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
prokaryotic expression, purification, and polyclonal antibody production of a truncated recombinant rabies virus l protein.rabies virus (rabv) is a deadly neurotropic virus that causes the disease of rabies in humans and animals. l protein is one of the large structural protein of rabies virus, which displays multiple enzymatic activities, and is required for viral transcription and replication.201528959286
direct conversion of human fibroblasts to functional excitatory cortical neurons integrating into human neural networks.human fibroblasts can be directly converted to several subtypes of neurons, but cortical projection neurons have not been generated.201728962665
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
recombinant newcastle disease virus rl-rvg enhances the apoptosis and inhibits the migration of a549 lung adenocarcinoma cells via regulating alpha 7 nicotinic acetylcholine receptors in vitro.the aim of this study were to investigate the possible pro-apoptotic mechanisms of the recombinant newcastle disease virus (ndv) strain rl-rvg, which expresses the rabies virus glycoprotein, in a549 lung adenocarcinoma cells via the regulation of alpha 7 nicotinic acetylcholine receptors (α7 nachrs) and to analyze the relationships between α7 nachr expression in lung cancer and the clinical pathological features.201728974241
safety, efficacy and immunogenicity evaluation of the sag2 oral rabies vaccine in formosan ferret badgers.since 2013, rabies cases have been reported among formosan ferret badgers in taiwan, and they have been shown to be the major reservoirs for taiwanese enzootics. to control and eradicate rabies, the authorities plan to implement a vaccination programme. before distributing live vaccines in the field, this study assessed the safety, efficacy, and immunogenicity of sag2 vaccine on ferret badgers by direct oral instillation. after application of 109 tcid50/dose, no virus was excreted into the oral ...201728977009
rabies virus modifies host behaviour through a snake-toxin like region of its glycoprotein that inhibits neurotransmitter receptors in the cns.rabies virus induces drastic behaviour modifications in infected hosts. the mechanisms used to achieve these changes in the host are not known. the main finding of this study is that a region in the rabies virus glycoprotein, with homologies to snake toxins, has the ability to alter behaviour in animals through inhibition of nicotinic acetylcholine receptors present in the central nervous system. this finding provides a novel aspect to virus receptor interaction and host manipulation by pathogen ...201728993633
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
near-infrared fluorescent protein irfp720 is optimal for in vivo fluorescence imaging of rabies virus infection.in vivo imaging is a noninvasive method that enables real-time monitoring of viral infection dynamics in a small animal, which allows a better understanding of viral pathogenesis. in vivo bioluminescence imaging of virus infection is widely used but, despite its advantage over bioluminescence that no substrate administration is required, fluorescence imaging is not used because of severe autofluorescence. recently, several far-red and near-infrared (nir) fluorescent proteins (fps) have been deve ...201729039733
census and vaccination coverage of owned dog populations in four resource-limited rural communities, mpumalanga province, south africa.dogs (canis familiaris) are often free-roaming in sub-saharan african countries. rabies virus circulates in many of these populations and presents a public health issue. mass vaccination of dog populations is the recommended method to decrease the number of dog and human rabies cases. we describe and compare four populations of dogs and their vaccination coverage in four different villages (hluvukani, athol, utah and dixie) in bushbuckridge municipality, mpumalanga province, south africa. cross- ...201729041786
efficacy of the oral rabies virus vaccine strain spbn gasgas in foxes and raccoon dogs.to test the immunogenicity and efficacy of a new oral rabies virus vaccine strain spbn gasgas in wildlife target species, one group of foxes and two groups of raccoon dogs were offered a bait containing 1.7 ml of the vaccine (106.6 ffu/ml; 106.8 ffu/dose) and subsequently challenged approximately 180 days later with a fox rabies virus isolate. one group of raccoon dogs (n=30) received the same challenge dose (100.7 micld50/ml) as the red foxes (n=29). the other group with raccoon dogs (n=28) tog ...201729042202
development and characterization of novel chimeric monoclonal antibodies for broad spectrum neutralization of rabies virus.current post-exposure prophylaxis for rabies virus infection has several limitations in terms of supply, cost, safety, and efficacy. attempts to replace human or equine rabies immune globulins (hrig or erig) have been made by several companies and institutes. we developed potent monoclonal antibodies to neutralize a broad spectrum of rabies viruses by screening hybridomas received from the u.s. centers for disease control and prevention (cdc). two kinds of chimeric human antibodies (chimeric #7 ...201729045436
evaluation of immune responses in dogs to oral rabies vaccine under field conditions.during the 20th century parenteral vaccination of dogs at central-point locations was the foundation of successful canine rabies elimination programs in numerous countries. however, countries that remain enzootic for canine rabies have lower infrastructural development compared to countries that have achieved elimination, which may make traditional vaccination methods less successful. alternative vaccination methods for dogs must be considered, such as oral rabies vaccine (orv). in 2016, a tradi ...201729054727
inhibition of rabies virus replication by interferon-stimulated gene 15 and its activating enzyme uba7.it was reported that isg15 and its activating enzyme uba7 have antiviral functions. however, there is no study to demonstrate whether isg15 and uba7 have anti-rabies virus function. in the current study, in vivo and in vitro anti-rabies virus function of isg15 and uba7 were investigated using rnai technology. the results showed that shrna knock-down of expression of isg15 and uba7 increased the titers of rabv in neuroblastoma cell line na and microglial cell line bv-2 cells and shrna knockdown o ...201729056542
neuronal lrp4 regulates synapse formation in the developing cns.the low-density lipoprotein receptor-related protein 4 (lrp4) is essential in muscle fibers for the establishment of the neuromuscular junction. here, we show that lrp4 is also expressed by embryonic cortical and hippocampal neurons, and that downregulation of lrp4 in these neurons causes a reduction in density of synapses and number of primary dendrites. accordingly, overexpression of lrp4 in cultured neurons had the opposite effect inducing more but shorter primary dendrites with an increased ...201729061639
molecular characterization and phylogenetic relatedness of dog-derived rabies viruses circulating in cameroon between 2010 and 2016.rabies is enzootic among dog populations in some parts of cameroon and the risk of human rabies is thought to be steadily high in these regions. however, the molecular epidemiology of circulating rabies virus (rabv) has been hardly considered in cameroon as well as in most neighboring central african countries. to address this fundamental gap, 76 nucleoprotein (n) gene sequences of dog-derived rabv were obtained from 100 brain specimens sampled in cameroon from 2010 to 2016. studied sequences we ...201729084223
regulation of nf-κb by the p105-abin2-tpl2 complex and relap43 during rabies virus infection.at the crossroad between the nf-κb and the mapk pathways, the ternary complex composed of p105, abin2 and tpl2 is essential for the host cell response to pathogens. the matrix protein (m) of field isolates of rabies virus was previously shown to disturb the signaling induced by relap43, a nf-κb protein close to rela/p65. here, we investigated how the m protein disturbs the nf-κb pathway in a relap43-dependant manner and the potential involvement of the ternary complex in this mechanism. using a ...201729084252
terrestrial animal-derived rabies virus in a juvenile indian flying fox in sri lanka. 201729093322
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
a translational study on looming-evoked defensive response and the underlying subcortical pathway in autism.rapidly approaching objects indicating threats can induce defensive response through activating a subcortical pathway comprising superior colliculus (sc), lateral posterior nucleus (lp), and basolateral amygdala (bla). abnormal defensive response has been reported in autism, and impaired synaptic connections could be the underlying mechanism. whether the sc-lp-bla pathway processes looming stimuli abnormally in autism is not clear. here, we found that looming-evoked defensive response is impaire ...201729116187
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
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
study of rabies virus by differential scanning calorimetry.differential scanning calorimetry (dsc) has been used in the past to study the thermal unfolding of many different viruses. here we present the first dsc analysis of rabies virus. we show that non-inactivated, purified rabies virus unfolds cooperatively in two events centered at approximately 62 and 73 °c. beta-propiolactone (bpl) treatment does not alter significantly viral unfolding behavior, indicating that viral inactivation does not alter protein structure significantly. the first unfolding ...201529124221
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
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
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
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
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
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
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 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
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
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
[rabies virus induces the formation of stress granules, which are in close proximity to viral factories]. 201729200383
[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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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