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real-time imaging of rabies virus entry into living vero cells.understanding the mechanism of rabies virus (rabv) infection is vital for prevention and therapy of virulent rabies. however, the infection mechanism remains largely uncharacterized due to the limited methods and viral models. herein, we utilized a powerful single-virus tracking technique to dynamically and globally visualize the infection process of the live attenuated rabies vaccine strain-srv9 in living vero cells. firstly, it was found that the actin-enriched filopodia is in favor of virus r ...201526148807
a dynein light chain 1 binding motif in rabies virus polymerase l protein plays a role in microtubule reorganization and viral primary transcription.rabies virus (rabv) polymerase l together with phosphoprotein p forms the pl polymerase complex that is essential for replication and transcription. however, its exact mechanism of action, interactions with cellular factors, and intracellular distribution are yet to be understood. here by imaging a fluorescently tagged polymerase (mcherry-rabv-l), we show that l accumulates at acetylated and reorganized microtubules (mt). in silico analysis revealed a dynein light chain 1 (dlc1) binding motif in ...201526157129
in vivo reprogramming of striatal ng2 glia into functional neurons that integrate into local host circuitry.the possibility of directly converting non-neuronal cells into neurons in situ in the brain would open therapeutic avenues aimed at repairing the brain after injury or degenerative disease. we have developed an adeno-associated virus (aav)-based reporter system that allows selective gfp labeling of reprogrammed neurons. in this system, gfp is turned on only in reprogrammed neurons where it is stable and maintained for long time periods, allowing for histological and functional characterization o ...201526166567
comparison of automated quantitative reverse transcription-pcr and direct fluorescent-antibody detection for routine rabies diagnosis in the united states.rabies virus found worldwide and prevalent throughout the united states continues to be a public health concern. direct-fluorescent antibody (dfa) detection remains the gold standard for rabies virus diagnostics. assessing the utility of a high-throughput molecular platform such as the qiasymphony sp/as, in conjunction with quantitative reverse transcription-pcr (qrt-pcr), to augment or potentially replace the dfa test, was the focus of this project. here we describe a triplex qrt-pcr assay, inc ...201526179300
[two cases of hydrophobia in the republic of tatarstan: in vivo and postmortem laboratory diagnosis].the results of rabies in vivo and postmortem laboratory detection in two cases registered in the republic of tatarstan are reported: a victim bitten by a wolf in 2002 and another one bitten by a stray dog on goa island, india, in 2013. in the patient bitten by a wolf cornea imprints studies using the method of fluorescent antibodies (mfa) showed rabies-positive result 6 days before the patient's death. the results were confirmed by postmortem examination of different parts of the brain and saliv ...201526182652
factors impacting the control of rabies.rabies is a classical zoonosis that has been known to man for ages. the disease can be caused by several viral species in the lyssavirus genus, but the type species, rabies virus (rabv), is by far the most important from a zoonosis perspective. the extreme neurotropism of rabv and the evolutionarily conserved elements and structures of the mammalian brain suggest that this virus evolved an ultimate niche for replication, simultaneously exploiting classical social behavior of a wide diversity of ...201326184959
viral suppression function of intracellular antibody against c-terminal domain of rabies virus phosphoprotein.rabies virus (rv) causes a fatal disease in both human and animals. the disease can be prevented by post-exposure prophylaxis in individuals exposed to rv. however, the neutralization effect is limited after the virus enters into the host cells. so, it is important to identify new targets for rabies therapy. in this study, a human antibody rv1a2 specific to rv phosphoprotein (rv-p) was generated from a human naïve immune antibody library. the antibody recognized all forms of the phosphoproteins ...201526188200
resistance to rhabdoviridae infection and subversion of antiviral responses.interferon (ifn) treatment induces the expression of hundreds of ifn-stimulated genes (isgs). however, only a selection of their products have been demonstrated to be responsible for the inhibition of rhabdovirus replication in cultured cells; and only a few have been shown to play a role in mediating the antiviral response in vivo using gene knockout mouse models. ifns inhibit rhabdovirus replication at different stages via the induction of a variety of isgs. this review will discuss how indivi ...201526198243
receptor-mediated increase in rabies virus axonal transport. 201526199597
natural rabies infection in a domestic fowl (gallus domesticus): a report from india.rabies is a fatal encephalitis caused by viruses belonging to the genus lyssavirus of the family rhabdoviridae. it is a viral disease primarily affecting mammals, though all warm blooded animals are susceptible. experimental rabies virus infection in birds has been reported, but naturally occurring infection of birds has been documented very rarely.201526201090
itraq protein profile analysis of neuroblastoma (na) cells infected with the rabies viruses rhep-flury and hep-dg.the rabies virus (rabv) glycoprotein (g) is the principal contributor to the pathogenicity and protective immunity of rabv. in a previous work, we reported that recombinant rabies virus hep-dg, which was generated by reverse genetics to carry two copies of the g-gene, showed lower virulence than the parental virus rhep-flury in suckling mice with a better immune protection effect. to better understand the mechanisms underlying rabies virus attenuation and the role of glycoprotein g, isobaric tag ...201526217322
exposure to rabies in small indian mongooses (herpestes auropunctatus) from two regions in puerto rico.the small indian mongoose (herpestes auropunctatus) was introduced to several caribbean islands to control rat (rattus spp.) damage to sugarcane plantations. mongooses failed at suppressing rat populations and are now considered pests throughout most of their introduced range. importantly, mongooses are rabies reservoirs on several caribbean islands. in puerto rico, mongooses have been implicated in up to 70% of reported animal rabies cases. there is no rabies vaccination program for wildlife in ...201526251987
rabies surveillance among bats in tennessee, usa, 1996-2010.rabies virus (rabv) infects multiple bat species in the americas, and enzootic foci perpetuate in bats principally via intraspecific transmission. in recent years, bats have been implicated in over 90% of human rabies cases in the us. in tennessee, two human cases of rabies have occurred since 1960: one case in 1994 associated with a tricolored bat (perimyotis subflavus) rabv variant and another in 2002 associated with the tricolored/silver-haired bat (p. subflavus/lasionycteris noctivagans) rab ...201526251992
[from the connectome to brain function: rabies virus tools for elucidating structure and function of neural circuits]. 201526256748
rabies virus infection in ferret badgers (melogale moschata subaurantiaca) in taiwan: a retrospective study.fifteen ferret badgers (melogale moschata subaurantiaca), collected 2010-13 and stored frozen, were submitted for rabies diagnosis by direct fluorescent antibody test and reverse transcription pcr. we detected seven positive animal samples, including some from 2010, which indicated that the ferret badger population in taiwan had been affected by rabies prior to 2010.201526267459
application of recombinant adenoviruses expressing glycoprotein or nucleoprotein of rabies virus to korean raccoon dogs.a new rabies vaccine for animals, including raccoon dogs, in korea is needed to eradicate rabies infection. in this study, we constructed two recombinant adenoviruses expressing the glycoprotein or nucleoprotein of the rabies virus (rabv). we then investigated the safety and immunogenicity of these strains in raccoon dogs, depending on inoculation route.201526273578
awareness of rabies prevention and control measures among public health workers in northern vietnam.to assess and compare rabies related knowledge and awareness of public health workers at provincial and district levels in the seven provinces with the highest number of deaths from human rabies in northern vietnam.201526278473
a pathological study of the salivary glands of rabid dogs in the philippines.rabies is a zoonotic disease caused by the rabies virus. while the salivary glands are important as exit and propagation sites for the rabies virus, the mechanisms of rabies excretion remain unclear. here, we investigated the histopathology of the salivary glands of rabid dogs and analyzed the mechanism of excretion into the oral cavity. mandibular and parotid glands of 22 rabid dogs and three control dogs were used. mild to moderate non-suppurative sialadenitis was observed in the mandibular gl ...201626278996
spatio-temporal use of oral rabies vaccines in fox rabies elimination programmes in europe.in europe, the elimination of wildlife rabies using oral rabies vaccination [orv] of foxes for more than 30 years has been a success story. since a comprehensive review on the scope of the different oral rabies vaccine baits distributed across europe has not been available yet, we evaluated the use of different vaccine baits over the entire period of orv [1978-2014]. our findings provide valuable insights into the complexity of orv programs in terms of vaccine related issues. more than 10 oral v ...201526280895
assessment of 200 pediatric patients exposed to rabies risk.rabies is still an important health problem particularly in underdeveloped or developing countries. in this study, the aim was to investigate demographic characteristics and vaccination schedules of cases suspected of having rabies and admitted to the pediatric emergency clinic of our hospital, which serves as one of the rabies vaccination centers in our province.201526294146
[rabies vaccines: current status and prospects for development].rabies is an infectious disease among humans and animals that remains incurable, despite its longstanding research history. the only way to prevent the disease is prompt treatment, including vaccination as an obligatory component and administration of antirabies immunoglobulin as a supplement. since the first antirabies vaccination performed in the 19th century, a large number of different rabies vaccines have been developed. progress in molecular biology and biotechnology enabled the developmen ...201726299857
fluorescent antibody test, quantitative polymerase chain reaction pattern and clinical aspects of rabies virus strains isolated from main reservoirs in brazil.rabies virus (rabv) isolated from different mammals seems to have unique characteristics that influence the outcome of infection. rabv circulates in nature and is maintained by reservoirs that are responsible for the persistence of the disease for almost 4000 years. considering the different pattern of pathogenicity of rabv strains in naturally and experimentally infected animals, the aim of this study was to analyze the characteristics of rabv variants isolated from the main brazilian reservoir ...201526303004
local infiltration of rabies immunoglobulins without systemic intramuscular administration: an alternative cost effective approach for passive immunization against rabies.presently the dose of rabies immunoglobulin (rig) which is an integral part of rabies post exposure prophylaxis (pep) is calculated based on body weight though the recommendation is to infiltrate the wound(s). this practice demands large quantities of rig which may be unaffordable to many patients. in this background, we conducted this study to know if the quantity and cost of rig can be reduced by restricting passive immunization to local infiltration alone and avoiding systemic intramuscular a ...201626317441
dopamine neurons projecting to the posterior striatum form an anatomically distinct subclass.combining rabies-virus tracing, optical clearing (clarity), and whole-brain light-sheet imaging, we mapped the monosynaptic inputs to midbrain dopamine neurons projecting to different targets (different parts of the striatum, cortex, amygdala, etc) in mice. we found that most populations of dopamine neurons receive a similar set of inputs rather than forming strong reciprocal connections with their target areas. a common feature among most populations of dopamine neurons was the existence of den ...201526322384
a novel variable antibody fragment dimerized by leucine zippers with enhanced neutralizing potency against rabies virus g protein compared to its corresponding single-chain variable antibody fragment.fatal rabies can be prevented effectively by post-exposure prophylactic (pep) with rabies immunoglobulin (rig). single-chain variable fragments (scfv), which are composed of a variable heavy chain (vh) and a variable light chain (vl) connected by a peptide linker, can potentially be used to replace rig. however, in our previous study, a scfv (scfv57s) specific for the rabies virus (rv) g protein showed a lower neutralizing potency than that of its parent igg due to lower stability and altered pe ...201526325475
[bats and viruses: complex relationships].with more than 1 200 species, bats and flying foxes (order chiroptera) constitute the most important and diverse order of mammals after rodents. many species of bats are insectivorous while others are frugivorous and few of them are hematophagous. some of these animals fly during the night, others are crepuscular or diurnal. some fly long distances during seasonal migrations. many species are colonial cave-dwelling, living in a rather small home range while others are relatively solitary. howeve ...201526330152
ecological approaches in veterinary epidemiology: mapping the risk of bat-borne rabies using vegetation indices and night-time light satellite imagery.rabies remains a disease of significant public health concern. in the americas, bats are an important source of rabies for pets, livestock, and humans. for effective rabies control and prevention, identifying potential areas for disease occurrence is critical to guide future research, inform public health policies, and design interventions. to anticipate zoonotic infectious diseases distribution at coarse scale, veterinary epidemiology needs to advance via exploring current geographic ecology to ...201526338730
rewiring, forgetting and learning. commentary: a critical period for experience-dependent remodeling of adult-born neuron connectivity. 201526379485
instructive even after a decade: complete results of initial virological diagnostics and re-evaluation of molecular data in the german rabies virus "outbreak" caused by transplantations.in 2005, six patients in germany received solid organs and both corneas from a donor with an unrecognized rabies infection. initial virological diagnostics with the machinery available at the two national reference laboratories could quickly clarify the situation. rabies virus antigen was detected in the organ donor's brain. in two of the three recipients with neurological alterations, intra vitam diagnosis was achieved by conventional rt-pcrs. comparison of the phylogenetic relatedness of the d ...201526384867
beyond rabies: are free-ranging skunks (mephitis mephitis) in british columbia reservoirs of emerging infection?wild animal reservoirs are an important source of emerging and zoonotic infection. skunks (mephitis mephitis) are a reservoir of skunk strain rabies virus in canada, with the exception of some areas including the province of british columbia (bc). beyond rabies, the reservoir status of skunks for emerging and zoonotic pathogens in bc is unknown. from march 2011 to february 2015, 50 free-ranging skunks were necropsied and tested for 4 pathogens: influenza a, aleutian disease virus (adv), leptospi ...201726392297
identification and genetic characterization of rabies virus from egyptian water buffaloes (bubalus bubalis) bitten by a fox.rabies is caused by negative strand rna-virus classified in the genus lyssavirus, family rhabdoviridae of the order mononegavirales. the aim of the present study was to identify and analyze nucleotides sequence of nucleoprotein (n) gene of rabies virus (rabv) from two cases of water buffaloes (bubalus bubalis) bitten by a fox in egypt, 2013. the diseased buffaloes showed nervous manifestations with fever. specimens from brains of the buffaloes with suspected rabies were collected. rabv in collec ...201526396980
exogenous interferon prolongs survival of rabies infected mice.rabies is an acute viral infection that causes encephalomyelitis in almost all warm blooded animals and is invariably fatal once the clinical signs appear. the present study was carried out to assess the effect of recombinant human interferon alpha (rhifn α-2a) treatment on the survival of rabies infected mice and its correlation with cytokines expression. the gene expression of tnf-α and il-6 was measured by sybr green real time pcr for two groups-"pre-exposure" (mice were inoculated with rhifn ...201526396983
t-bet is required for the rapid clearance of attenuated rabies virus from central nervous system tissue.much of our understanding of cns immunity has been gained from models involving pathological inflammation. attenuated rabies viruses (rabv) are unique tools to study cns immunity in the absence of conventional inflammatory mechanisms, as they spread from the site of inoculation to the cns transaxonally, thereby bypassing the blood-brain barrier (bbb), and are cleared without neutrophil or monocyte infiltration. to better understand the role of cd4 t cell subsets in the clearance of the virus fro ...201526408670
analysis of subcellular prefoldin 1 redistribution during rabies virus infection.rabies virus (rabv) is one of the old deadly zoonotic viruses. it attacks the central nervous system and causes acute encephalitis in humans and animals. host factors are known to be essential for virus infection and replication in cells. the identification of the key host factors required for rabv infection may provide important information on rabv replication and may provide new potential targets for rabv drug discovery.201526421138
epidemiological profile of wild rabies in brazil (2002-2012).rabies is one of the most important zoonosis in the world with high impact on public health. studies report the presence of lyssavirus in reservoirs of the wild cycle, highlighting the role of wild canines, marmosets, and vampire and non-vampire bats as potential vectors of the disease to domestic animals and human beings. therefore, the reintroduction of rabies in urban environments from reservoirs of the wild cycle is a matter of concern. this study describes the profile of rabies cases docume ...201726423323
phylogenetic analysis of indian rabies virus isolates targeting the complete glycoprotein gene.rabies a fatal viral zoonosis is endemic in india. there is no report on phylogenetic study of indian rabies virus isolates based on the complete g gene. in the present study, a total of 25 rabies positive brain samples collected during 2001-2014 from north india (up, mp, delhi, rajasthan), south india (kerala and karnataka) and gujarat states belonging to six different host species were subjected to g gene amplification by rt-pcr as three overlapping fragments of 881 bp, 991 bp and 618 bp. phyl ...201526427850
recombinant rabies virus expressing dog gm-csf is an efficacious oral rabies vaccine for dogs.developing efficacious oral rabies vaccines is an important step to increase immunization coverage for stray dogs, which are not accessible for parenteral vaccination. our previous studies have demonstrated that recombinant rabies virus (rabv) expressing cytokines/chemokines induces robust protective immune responses after oral immunization in mice by recruiting and activating dendritic cells (dcs) and b cells. to develop an effective oral rabies vaccine for dogs, a recombinant attenuated rabv e ...201526436700
mapping neural circuits with clarity.the use of whole-brain imaging has shed new light on the organization of the dopamine system.201526452201
connectivity of mouse somatosensory and prefrontal cortex examined with trans-synaptic tracing.information processing in neocortical circuits requires integrating inputs over a wide range of spatial scales, from local microcircuits to long-range cortical and subcortical connections. we used rabies virus-based trans-synaptic tracing to analyze the laminar distribution of local and long-range inputs to pyramidal neurons in the mouse barrel cortex and medial prefrontal cortex (mpfc). in barrel cortex, we found substantial inputs from layer 3 (l3) to l6, prevalent translaminar inhibitory inpu ...201526457553
real-time rt-pcr for the detection of lyssavirus species.the causative agents of rabies are single-stranded, negative-sense rna viruses in the genus lyssavirus of rhabdoviridae, consisting of twelve classified and three as yet unclassified species including classical rabies virus (rabv). highly neurotropic rabv causes rapidly progressive encephalomyelitis with nearly invariable fatal outcome. rapid and reliable diagnosis of rabies is highly relevant for public and veterinary health. due to growing variety of the genus lyssavirus observed, the developm ...201426464934
λ-carrageenan p32 is a potent inhibitor of rabies virus infection.rabies, caused by rabies virus (rabv), is an acute, fatal encephalitic disease that affects many warm-blooded mammals. currently, post-exposure prophylaxis regimens are effective for most rabies cases, but once the clinical signs of the disease appear, current treatment options become ineffective. carrageenan has been reported as a potent inhibitor of many viruses. in this study, the λ-carrageenan (λ-cg) p32 was investigated for its potential role in inhibiting rabv infection. our results show t ...201526465753
critical role of k1685 and k1829 in the large protein of rabies virus in viral pathogenicity and immune evasion.rabies, one of the oldest infectious diseases, still presents a public health threat in most parts of the world today. its pathogen, rabies virus (rabv), can utilize its viral proteins, such as the nucleoprotein and phosphorylation protein, to subvert the host innate immune system. for a long time, the large (l) protein was believed to be essential for rabv transcription and replication, but its role in viral pathogenicity and immune evasion was not known. recent studies have found that the cons ...201526468538
[proteomic analyses of purified particles of the rabies virus].the rabies virus (rabv) is an enveloped rna virus. it mainly damages the central nervous system and causes anencephaly in mammals and humans. there is now compelling evidence that enveloped virions released from infected cells can carry many host proteins, some of which may play an important part in viral replication. several host proteins have been reported to be incorporated into rabv particles. however, a systematic study to reveal the proteomics of rabv particles has not been conducted. in t ...201526470524
a critical evaluation of drug delivery from ligand modified nanoparticles: confounding small molecule distribution and efficacy in the central nervous system.in this work, we sought to test how surface modification of poly(lactic-co-glycolic acid) (plga) nanoparticles with peptide ligand alters the brain specific delivery of encapsulated molecules. for biodistribution studies, nanoparticles modified with rabies virus glycoprotein (rvg29) were loaded with small molecule drug surrogates and administered to healthy mice by lateral tail vein injection. mice were perfused 2h after injection and major anatomical regions of the cns were dissected (striatum, ...201526471392
insect cell entrapment, growth and recovering using a single-use fixed-bed bioreactor. scaling up and recombinant protein production.insect cells are largely used for industrial production of vaccines, viral vectors and recombinant proteins as well as in research and development as an important tool for biology and bioprocess studies. they grow in suspension and are semi-adherent cells. among the cell culture systems enabling scalable bioprocess the single-use fixed-bed icellis(®) bioreactors offer great advantages. we have established the conditions for drosophila melanogaster schneider 2 (s2) and spodoptera frugiperda (sf9) ...201526481831
commentary: incorporation of membrane-anchored flagellin or escherichia coli heat-labile enterotoxin b subunit enhances the immunogenicity of rabies virus-like particles in mice and dogs. 201526483770
investigation of an imported case of rabies in a juvenile dog with atypical presentation.movement of dogs between rabies-endemic and rabies-free countries carries the inherent risk of introducing the disease. in april of 2008, a juvenile dog was imported to the uk from sri lanka. it died shortly after transfer to a quarantine facility in the south-east of england following a short history of diarrhoea and convulsions but no overt signs of aggression. subsequent investigation confirmed that rabies was the cause of death. rabies virus was isolated from brain samples taken from the dog ...201126486624
compounds derived from epigallocatechin-3-gallate (egcg) as a novel approach to the prevention of viral infections.pathogenic viral infections pose major health risks to humans and livestock due to viral infection-associated illnesses such as chronic or acute inflammation in crucial organs and systems, malignant and benign lesions. these lead to large number of illnesses and deaths worldwide each year. outbreaks of emerging lethal viruses, such as ebola virus, severe acute respiratory syndrome (sars) virus and middle east respiratory syndrome (mers) virus, could lead to epidemics or even pandemics if they ar ...201526490660
rabies epidemiology and control in ecuador.describe the epidemiology and the control effort for rabies in ecuador.201526493436
a vl-linker-vh orientation dependent single chain variable antibody fragment against rabies virus g protein with enhanced neutralizing potency in vivo.lethal rabies can be prevented effectively by post-exposure prophylactic (pep) with rabies immunoglobulin (rig). single-chain variable fragment (scfv), which is composed of a variable heavy chain (vh) and variable light chain (vl) connected by a peptide linker, may be developed as alternative to rig for neutralizing rabies virus (rv). however, our previously constructed scfv (fv57s) with the (nh2) vh-linker-vl (cooh) orientation showed a lower neutralizing potency than its parent rig. this orien ...201626497316
ebolavirus vaccines: progress in the fight against ebola virus disease.ebolaviruses are highly infectious pathogens that cause lethal ebola virus disease (evd) in humans and non-human primates (nhps). due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. in this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vacc ...201526535889
a case report on indirect transmission of human rabies.at present, virus infection is still a common threat to public health in developing countries. human rabies remains a matter of great global concern with a case-fatality of almost 100%. the rabies virus belongs to the neurotropic type of virus of the lyssavirus genus, and the disease presents as a deteriorating encephalomyelitis and is endemic throughout much of the world, particularly in africa and asia. previous data have shown that, globally, approximately 59 000 human deaths are caused by ra ...201526537216
government response to the discovery of a rabies virus reservoir species on a previously designated rabies-free island, taiwan, 1999-2014.taiwan had been considered rabies free since 1961. in 2013, taiwan confirmed the detection of rabies virus in wild taiwan ferret-badgers. up to december 2014, there have been 423 rabies-confirmed ferret-badgers and three cases of spillover infection into non-reservoir hosts. genetic analysis indicates that tfbv is distinct from all other known rabies virus variants. to date, ferret-badger rabies is known to occur only in china and taiwan. the temporal dynamics of rabid ferret-badgers in taiwan s ...201626542085
cationic amphiphilic drugs enhance entry of lentiviral particles pseudotyped with rabies virus glycoprotein into non-neuronal cells.amiodarone and other cationic amphiphilic drugs (cads) inhibit cell entry by diverse human pathogenic viruses including filoviruses, dengue virus and japanese encephalitis virus. they are thus considered potential broad spectrum antiviral agents. here we report the unexpected finding that amiodarone and other cads markedly enhance rabies virus (rabv) glycoprotein- (gp-) mediated cell entry of pseudotyped lentiviruses into non-neuronal cells but not in neuronal cells. increased cell entry can als ...201526542648
origins of multisynaptic projections from the basal ganglia to the forelimb region of the ventral premotor cortex in macaque monkeys.the ventral premotor cortex (pmv), occupying the ventral aspect of area 6 in the frontal lobe, has been implicated in action planning and execution based on visual signals. although the pmv has been characterized by cortico-cortical connections with specific subregions of the parietal and prefrontal cortical areas, a topographical input/output organization between the pmv and the basal ganglia (bg) still remains elusive. in the present study, retrograde transneuronal labelling with the rabies vi ...201626547510
afferent and efferent connections of c1 cells with spinal cord or hypothalamic projections in mice.the axonal projections and synaptic input of the c1 adrenergic neurons of the rostral ventrolateral medulla (vlm) were examined using transgenic dopamine-beta hydroxylase cre mice and modified rabies virus. cre-dependent viral vectors expressing tva (receptor for envelopea) and rabies glycoprotein were injected into the left vlm. envelopea-pseudotyped rabies-egfp glycoprotein-deficient virus (rabies-egfp) was injected 4-6 weeks later in either thoracic spinal cord (sc) or hypothalamus. tva immun ...201626560463
pathology and molecular detection of rabies virus in ferret badgers associated with a rabies outbreak in taiwan.until rabies virus (rabv) infection in taiwan ferret badgers (twfb; melogale moschata subaurantiaca) was diagnosed in mid-june 2013, taiwan had been considered rabies free for >50 yr. although rabies has also been reported in ferret badgers in china, the pathologic changes and distribution of viral antigens of ferret badger-associated rabies have not been described. we performed a comprehensive pathologic study and molecular detection of rabies virus in three necropsied rabid twfbs and evaluated ...201626560756
immunostained plaque assay for detection and titration of rabies virus infectivity.the fluorescent antibody test (fat) is the most commonly used method for detection of the rabies virus (rv). the plaque assay can only be applied to fixed rvs, and cannot be used for street rvs. in this study, plaque formation allowing the determination of both fixed and street rvs was achieved using the immune plaque assay. the immune plaque assay carried out using both fixed and street rvs showed the formation of clear and countable plaques after immunostaining with anti-rv p monoclonal antibo ...201626569350
optical imaging and gene therapy with neuroblastoma-targeting polymeric nanoparticles for potential theranostic applications.recently, targeted delivery systems based on functionalized polymeric nanoparticles have attracted a great deal of attention in cancer diagnosis and therapy. specifically, as neuroblastoma occurs in infancy and childhood, targeted delivery may be critical to reduce the side effects that can occur with conventional approaches, as well as to achieve precise diagnosis and efficient therapy. thus, biocompatible poly(d,l-lactide-co-glycolide) (plg) nanoparticles containing an imaging probe and therap ...201626573885
running rewires the neuronal network of adult-born dentate granule cells.exercise improves cognition in humans and animals. running increases neurogenesis in the dentate gyrus of the hippocampus, a brain area important for learning and memory. it is unclear how running modifies the circuitry of new dentate gyrus neurons to support their role in memory function. here we combine retroviral labeling with rabies virus mediated trans-synaptic retrograde tracing to define and quantify new neuron afferent inputs in young adult male c57bl/6 mice, housed with or without a run ...201626589333
recent advances in the development of vaccines for ebola virus disease.ebola virus is one of the most dangerous microorganisms in the world causing hemorrhagic fevers in humans and non-human primates. ebola virus (ebov) is a zoonotic infection, which emerges and re-emerges in human populations. the 2014 outbreak was caused by the zaire strain, which has a kill rate of up to 90%, though 40% was recorded in the current outbreak. the 2014 outbreak is larger than all 20 outbreaks that have occurred since 1976, when the virus was first discovered. it is the first time t ...201626596227
altering entry site preference of lentiviral vectors into neuronal cells by pseudotyping with envelope glycoproteins.a lentiviral vector system provides a powerful strategy for gene therapy trials against a variety of neurological and neurodegenerative disorders. pseudotyping of lentiviral vectors with different envelope glycoproteins not only confers the neurotropism to the vectors, but also alters the preference of sites of vector entry into neuronal cells. one major group of lentiviral vectors is a pseudotype with vesicular stomatitis virus glycoprotein (vsv-g) that enters preferentially cell body areas (so ...201626611586
monoclonal antibodies for characterization of rabies virus isolated from non-hematophagous bats in brazil.in brazil, various isolates of rabies virus (rabv) show antigenic profiles distinct from those established by the reduced panel of eight monoclonal antibodies (mabs) determined by the centers for disease control and prevention (cdc), utilized for the antigenic characterization of rabv in the americas. the objective of this study was to produce mabs from rabv isolates from insectivorous bats with an antigenic profile incompatible with the pre-established one.201526623633
pseudotyping of g-gene-deficient rabies virus.g-deleted fluorescent rabies virus (rv) pseudotyped with rv g proteins, sad δg egfp (rv cvs-g), can be used as single-round vectors for efficient retrograde labeling of neurons. for these experiments, as well as for monosynaptic tracing, which involves pseudotyping in situ, the use of the cvs strain g is recommended because of its high tropism for neurons. pseudotype virus stocks generated by transfection of pcaggs-g (or in mg139-on cells) contain the g protein of the vaccine strain sad l16, whi ...201526631128
recombinant fluorescent rabies virus vectors for tracing neurons and synaptic connections.recombinant rabies virus (rv) vectors expressing fluorescent proteins allow staining of neurons from many mammalian species and enable the study of neuron morphology. because viral spread occurs only between neurons that have synaptic connections, these vectors also permit transsynaptic tracing. a recently established system for restriction of transsynaptic tracing to a single transsynaptic jump, dubbed monosynaptic tracing, uses glycoprotein gene-defective, pseudotyped rv. this allows infection ...201526631133
why has canine rabies remained endemic in the kilosa district of tanzania? lessons learnt and the way forward.domestic dogs are the main targets for rabies control as they are the principal reservoir for transmission of the rabies virus to humans and other domestic animals. the purpose of this study was to identify the factors that contribute to the rabies virus infecting the human population in a rural community of eastern tanzania.201526631275
the yin and yang of antiviral innate immunity in central nervous system.the innate immune system provides protection against invading neurotropic viruses. it acts as the first line of defense against invading viruses and plays an elementary role in their pathogenesis. the list of viruses capable of infecting human central nervous system (cns) is quite long, most important of them are japanese encephalitis virus (jev), rabies virus, west nile virus (wnv), herpes simplex virus (hsv), st. louis encephalitis virus (slev), la crosse virus, tick borne encephalitis virus ( ...201626635264
synergic effects between ocellatin-f1 and bufotenine on the inhibition of bhk-21 cellular infection by the rabies virus.rabies is an incurable neglected zoonosis with worldwide distribution characterized as a lethal progressive acute encephalitis caused by a lyssavirus. animal venoms and secretions have long been studied as new bioactive molecular sources, presenting a wide spectrum of biological effects, including new antiviral agents. bufotenine, for instance, is an alkaloid isolated from the skin secretion of the anuran rhinella jimi that inhibits cellular penetration by the rabies virus. antimicrobial peptide ...201526635873
herbal plants and plant preparations as remedial approach for viral diseases.herbal plants, plant preparations and phytoconstituents have proved useful in attenuating infectious conditions and were the only remedies available, till the advent of antibiotics (many being of plant origin themselves). among infectious diseases, viral diseases in particular, remain the leading cause of death in humans globally. a variety of phytoconstituents derived from medicinal herbs have been extensively studied for antiviral activity. based on this rationale, an online search was perform ...201526645032
molecular and immunogenic characterization of bhk-21 cell line adapted cvs-11 strain of rabies virus and future prospect in vaccination strategy.development of a cost effective quality vaccine is a key issue in rabies control programme in developing countries. with this perspective, in the present study, challenge virus standard (cvs)-11 strain of rabies virus was adapted to grow in bhk-21 cells, characterized, compared with other viruses including global vaccine strains and field isolates from indian subcontinent and china at molecular level. this cell adapted virus was evaluated for the production of cost effective veterinary vaccine. ...201526645040
growth signalobody selects functional intrabodies in the mammalian cytoplasm.a versatile strategy to inhibit protein functions in the cytoplasmic environment is eagerly anticipated for drug discovery. in this study, we demonstrate a novel system to directly select functional intrabodies from a library in the mammalian cytoplasm. in this system, a target homo-oligomeric antigen is expressed together with a single-chain fv (scfv) library that is linked to the cytoplasmic domain of a receptor tyrosine kinase (rtk) in the cytoplasm of murine interleukin-3 (il-3)-dependent ce ...201626647155
contribution of the interaction between the rabies virus p protein and i-kappa b kinase ϵ to the inhibition of type i ifn induction signalling.the p protein of rabies virus (rabv) is known to interfere with the phosphorylation of the host ifn regulatory factor 3 (irf-3) and to consequently inhibit type i ifn induction. previous studies, however, have only tested p proteins from laboratory-adapted fixed virus strains, and to the best of our knowledge there is no report about the effect of p proteins from street rabv strains or other lyssaviruses on the irf-3-mediated type i ifn induction system. in this study, we evaluated the inhibitor ...201626647356
immunoenhancement with flagellin as an adjuvant to whole-killed rabies vaccine in mice.vaccination is the most effective method for preventing rabies virus (rabv) infection in both humans and animals; however, no satisfactory vaccine has been developed for use worldwide. in the present study, we investigated the immunoadjuvant properties of salmonella typhimurium flagellin (fljb, flic, and fljb'-flic) to improve immune responses against the rabies vaccine (rv) and the protective efficacy of the whole-killed rabies vaccine (wkrv) with or without flagellins in balb/c mice. we also c ...201626650039
rabies virus phosphoprotein interacts with ribosomal protein l9 and affects rabies virus replication.rabies virus is a highly neurotropic virus that can cause fatal infection of the central nervous system in warm-blooded animals. the rabv phosphoprotein (p), an essential cofactor of the virus rna-dependent rna polymerase, is required for virus replication. in this study, the ribosomal protein l9, which has functions in protein translation, is identified as p-interacting cellular factor using phage display analysis. direct binding between the l9 and p was confirmed by protein pull-down and co-im ...201626655239
efficacy of favipiravir (t-705) in rabies postexposure prophylaxis.rabies is a fatal encephalitis caused by rabies virus (rabv), and no antiviral drugs for rabv are currently available. we report for the first time the efficacy of favipiravir (t-705) against rabv in vitro and in vivo. t-705 produced a significant, 3-4 log10 reduction in the multiplication of street and fixed rabv strains in mouse neuroblastoma neuro-2a cells, with half-maximal inhibitory concentrations of 32.4 µm and 44.3 µm, respectively. t-705 significantly improved morbidity and mortality am ...201526655300
interspecific contact and competition may affect the strength and direction of disease-diversity relationships for directly transmitted microparasites.the frequency of opportunities for transmission is key to the severity of directly transmitted disease outbreaks in multihost communities. transmission opportunities for generalist microparasites often arise from competitive and trophic interactions. additionally, contact heterogeneities within and between species either hinder or promote transmission. general theory incorporating competition and contact heterogeneities for disease-diversity relationships is underdeveloped. here, we present a fo ...201526655572
abortively infected astrocytes appear to represent the main source of interferon beta in the virus-infected brain.interferon beta (ifn-β) is a key component of cellular innate immunity in mammals, and it constitutes the first line of defense during viral infection. studies with cultured cells previously showed that almost all nucleated cells are able to produce ifn-β to various extents, but information about the in vivo sources of ifn-β remains incomplete. by applying immunohistochemistry and employing conditional-reporter mice that express firefly luciferase under the control of the ifn-β promoter in eithe ...201526656686
molecular and mathematical modeling analyses of inter-island transmission of rabies into a previously rabies-free island in the philippines.rabies is endemic in the philippines and dog bites are a major cause of rabies cases in humans. the rabies control program has not been successful in eliminating rabies because of low vaccination coverage among dogs. therefore, more effective and feasible strategies for rabies control are urgently required in the country. to control rabies, it is very important to know if inter-island transmission can occur because rabies can become endemic once the virus is introduced in areas that previously h ...201626656835
effect of nicotinic acetylcholine receptor alpha 1 (nachrα1) peptides on rabies virus infection in neuronal cells.rabies virus (rabv) is neurotropic and causes acute progressive encephalitis. herein, we report the interaction of nachrα1-subunit peptides with rabv and the effect of these peptides on rabv infection in cultured neuronal cells. peptide sequences derived from torpedo, bovine, human and rats were synthesized and studied for their interactions with rabv using virus capture elisa and peptide immunofluorescence. the results showed specific binding of the nachrα1-subunit peptides to the rabv. in the ...201626656837
population structure of two rabies hosts relative to the known distribution of rabies virus variants in alaska.for pathogens that infect multiple species, the distinction between reservoir hosts and spillover hosts is often difficult. in alaska, three variants of the arctic rabies virus exist with distinct spatial distributions. we tested the hypothesis that rabies virus variant distribution corresponds to the population structure of the primary rabies hosts in alaska, arctic foxes (vulpes lagopus) and red foxes (vulpes vulpes) to possibly distinguish reservoir and spillover hosts. we used mitochondrial ...201626661691
[molecular genetic characteristics of the virus isolated from patients with human acute encephalomyelitis and multiple sclerosis].the study of the antigenic and molecular genetic structure of human acute encephalomyelitis virus (haev) showed a high similarity of the haev n gene with the homologous gene of the fixed rabies virus strain. the results of the nucleotide sequence analysis indicate that haev belongs to the lyssavirus genotype 1. the n gene sequence is the closest to those of the era-cb20-m and rv-97 strains of the rabies virus. the need for further research into the role of the human acute encephalomyelitis virus ...201526665429
transolfactory neuroinvasion by viruses threatens the human brain.viral neuroinvasion via the olfactory system has been investigated in a variety of virus-animal models by scientists in many fields including virologists, pathologists, and neurologists. in humans, herpes simplex virus type 1 (hsv-1), human herpesvirus 6 (hhv-6), borna disease virus, rabies virus, and influenza a virus have been shown to take the olfactory route for neuroinvasion based on forensic and post-mortem specimens. this article briefly summarizes the anatomy, physiology, and immunology ...201526666182
single- versus double-dose rabies vaccination in captive african wild dogs (lycaon pictus).the immune responses of 35 captive african wild dogs (lycaon pictus) to an inactivated rabies virus vaccine were evaluated. seventeen animals received one 1-ml dose of inactivated rabies vaccine administered intramuscularly, while 18 received two 1-ml doses given simultaneously but at different injection sites. sera were collected from all animals prior to vaccination and intermittently from a subset of animals between 3 and 49 mo postvaccination. rabies neutralizing serum antibody titers were m ...201526667524
rabies in a dog imported from egypt with a falsified rabies vaccination certificate--virginia, 2015.canine rabies virus variant has been eliminated in the united states and multiple other countries. globally, however, dogs remain the principal source for human rabies infections. the world health organization recommends that when dogs cross international borders, national importing authorities should require an international veterinary certificate attesting that the animal did not show signs of rabies at the time of shipment, was permanently identified, vaccinated, or revaccinated, and had been ...201526678293
correlation of inducible nitric oxide synthase (inos) inhibition with tnf-α, caspase-1, fasl and tlr-3 in pathogenesis of rabies in mouse model.the role of inflammatory cytokines such as interleukin-1α/β (il-1α/β), il-6, il-10, tumour necrosis factor-alpha (tnf-α), interferons, nitric oxide (no) and inducible nitric oxide synthase (inos) in pathogenesis of rabies is being actively pursued. presently, levels of certain immune molecules in pathogenesis of rabies in mice have been investigated. cvs strain of rabies infection resulted in early increase in inos, tnf-α, caspase-1, fas ligand (fasl) and toll-like receptor-3 (tlr-3) mrna levels ...201626690069
factors associated with dog rabies immunisation status in bamako, mali.we conducted a cross-sectional survey in bamako, mali, to determine for the first time the seroprevalence of rabies virus antibodies in the dog population and people's knowledge, attitudes and practices (kap) towards the disease and its control. antibody detection was done with the fluorescent antibody virus neutralisation (favn) test, with a positivity threshold of 0.25iu/ml. we visited 2956 households in 2010 and 2011 and found 379 dogs in 279 households. data were collected on 279 dog-owning ...201726691990
evidence of two distinct phylogenetic lineages of dog rabies virus circulating in cambodia.this first extensive retrospective study of the molecular epidemiology of dog rabies in cambodia included 149 rabies virus (rabv) entire nucleoprotein sequences obtained from 1998-2011. the sequences were analyzed in conjunction with rabvs from other asian countries. phylogenetic reconstruction confirmed the south-east asian phylogenetic clade comprising viruses from cambodia, vietnam, thailand, laos and myanmar. the present study represents the first attempt to classify the phylogenetic lineage ...201626705238
profile of cytokines and chemokines triggered by wild-type strains of rabies virus in mice.rabies is a lethal infectious disease that causes 55,000 human deaths per year and is transmitted by various mammalian species, such as dogs and bats. the host immune response is essential for avoiding viral progression and promoting viral clearance. cytokines and chemokines are crucial in the development of an immediate antiviral response; the rabies virus (rabv) attempts to evade this immune response. the virus's capacity for evasion is correlated with its pathogenicity and the host's inflamma ...201626711511
early postnatal maturation in vestibulospinal pathways involved in neck and forelimb motor control.to assess the organization and functional development of vestibulospinal inputs to cervical motoneurons (mns), we have used electrophysiology (ventral root and electromyographic [emg] recording), calcium imaging, trans-synaptic rabies virus (rv) and conventional retrograde tracing and immunohistochemistry in the neonatal mouse. by stimulating the viiith nerve electrically while recording synaptically mediated calcium responses in mns, we characterized the inputs from the three vestibulospinal tr ...201626724676
anterograde or retrograde transsynaptic circuit tracing in vertebrates with vesicular stomatitis virus vectors.viruses have been used as transsynaptic tracers, allowing one to map the inputs and outputs of neuronal populations, due to their ability to replicate in neurons and transmit in vivo only across synaptically connected cells. to date, their use has been largely restricted to mammals. in order to explore the use of such viruses in an expanded host range, we tested the transsynaptic tracing ability of recombinant vesicular stomatitis virus (rvsv) vectors in a variety of organisms. successful infect ...201626729030
characterization of dendritic morphology and neurotransmitter phenotype of thoracic descending propriospinal neurons after complete spinal cord transection and gdnf treatment.after spinal cord injury (sci), poor regeneration of damaged axons of the central nervous system (cns) causes limited functional recovery. this limited spontaneous functional recovery has been attributed, to a large extent, to the plasticity of propriospinal neurons, especially the descending propriospinal neurons (dpsns). compared with the supraspinal counterparts, dpsns have displayed significantly greater regenerative capacity, which can be further enhanced by glial cell line-derived neurotro ...201626730519
inactivation of rabies virus by hydrogen peroxide.development of safe and protective vaccines against infectious pathogens remains a challenge. inactivation of rabies virus is a critical step in the production of vaccines and other research reagents. beta-propiolactone (βpl); the currently used inactivating agent for rabies virus is expensive and proved to be carcinogenic in animals. this study aimed to investigate the ability of hydrogen peroxide (h2o2) to irreversibly inactivate rabies virus without affecting its antigenicity and immunogenici ...201626731189
[the infectious and pathogenic characteristics of rabies virus strain ctncec25].to investigate the phenotypic characteristics of the strain of the rabies virus ctncec25, the strain of the china rabies virus ctn-1 adapted to primary chicken embryo cells (cecs), vero cells, and mouse neuroblastoma n2a cells was inoculated with ctncec25 and parental ctn-1 strains to explore the cytopathic effect (cpe) and growth kinetics of ctncec25 on cultured cells. to determine the pathogenicity of ctncec25, suckling mice, adult mice, guinea pigs and rabbits were inoculated with ctncec25 vi ...201526738284
theranostic gas-generating nanoparticles for targeted ultrasound imaging and treatment of neuroblastoma.the development of safe and efficient diagnostic/therapeutic agents for treating cancer in clinics remains challenging due to the potential toxicity of conventional agents. although the annual incidence of neuroblastoma is not that high, the disease mainly occurs in children, a population vulnerable to toxic contrast agents and therapeutics. we demonstrate here that cancer-targeting, gas-generating polymeric nanoparticles are useful as a theranostic tool for ultrasound (us) imaging and treating ...201626739549
intravenous administration of brain-targeted stable nucleic acid lipid particles alleviates machado-joseph disease neurological phenotype.others and we showed that rna interference holds great promise for the treatment of dominantly inherited neurodegenerative disorders such as machado-joseph disease (mjd), for which there is no available treatment. however, successful experiments involved intracranial administration of viral vectors and there is a need for a safer and less invasive procedure. in this work, we successfully generated stable nucleic acid lipid particles (snalps), incorporating a short peptide derived from rabies vir ...201626757259
a novel rabies vaccine based-on toll-like receptor 3 (tlr3) agonist pika adjuvant exhibiting excellent safety and efficacy in animal studies.vaccination alone is not sufficiently effective to protect human from post-exposure rabies virus infection due to delayed generation of rabies virus neutralizing antibodies and weak cellular immunity. therefore, it is vital to develop safer and more efficacious vaccine against rabies. pika, a stabilized chemical analog of double-stranded rna that interacts with tlr3, was employed as adjuvant of rabies vaccine. the efficacy and safety of pika rabies vaccine were evaluated. the results showed that ...201626765968
a simple alternative to stereotactic injection for brain specific knockdown of mirna.micrornas (mirnas) are key regulators of gene expression. in the brain, vital processes like neurodevelopment and neuronal functions depend on the correct expression of micrornas. perturbation of micrornas in the brain can be used to model neurodegenerative diseases by modulating neuronal cell death. currently, stereotactic injection is used to deliver mirna knockdown agents to specific location in the brain. here, we discuss strategies to design antagomirs against mirna with locked nucleotide m ...201526779762
rabies virus cvs-n2c(δg) strain enhances retrograde synaptic transfer and neuronal viability.virally based transsynaptic tracing technologies are powerful experimental tools for neuronal circuit mapping. the glycoprotein-deletion variant of the sad-b19 vaccine strain rabies virus (rabv) has been the reagent of choice in monosynaptic tracing, since it permits the mapping of synaptic inputs to genetically marked neurons. since its introduction, new helper viruses and reagents that facilitate complementation have enhanced the efficiency of sad-b19(δg) transsynaptic transfer, but there has ...201626804990
bioecological drivers of rabies virus circulation in a neotropical bat community.in addition to the commonly accepted importance of the vampire bat in the maintenance and transmission of the rabies virus (rabv) in south america, rabv infection of other species is widely evidenced, challenging their role in the viral cycle.201626808820
silencing ccr2 in macrophages alleviates adipose tissue inflammation and the associated metabolic syndrome in dietary obese mice.adipose tissue macrophage (atm)-mediated inflammation is a key feature contributing to the adverse metabolic outcomes of dietary obesity. recruitment of macrophages to obese adipose tissues (at) can occur through the engagement of ccr2, the receptor for mcp-1 (monocyte chemoattractant protein-1), which is expressed on peripheral monocytes/macrophages. here, we show that i.p. administration of a rabies virus glycoprotein-derived acetylcholine receptor-binding peptide effectively delivers complexe ...201626812653
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