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innate immune responses in raccoons after raccoon rabies virus infection.zoonotic wildlife diseases pose significant health risks not only to their primary vectors but also to humans and domestic animals. rabies is a lethal encephalitis caused by rabies virus (rv). this rna virus can infect a range of terrestrial mammals but each viral variant persists in a particular reservoir host. active management of these host vectors is needed to minimize the negative impacts of this disease, and an understanding of the immune response to rv infection aids strategies for host v ...201424085257
prevention and control of rabies in an age of global travel: a review of travel- and trade-associated rabies events--united states, 1986-2012.rabies prevention and control efforts have been successful in reducing or eliminating virus circulation regionally through vaccination of specific reservoir populations. a notable example of this success is the elimination of canine rabies virus variant from the united states and many other countries. however, increased international travel and trade can pose risks for rapid, long-distance movements of ill or infected persons or animals. such travel and trade can result in human exposures to rab ...201423870674
very-long-range disynaptic v1 connections through layer 6 pyramidal neurons revealed by transneuronal tracing with rabies virus.neurons in primary visual cortex (v1) integrate across the representation of the visual field through networks of long-range projecting pyramidal neurons. these projections, which originate from within v1 and through feedback from higher visual areas, are likely to play a key role in such visual processes as low contrast facilitation and extraclassical surround suppression. the extent of the visual field representation covered by feedback is generally much larger than that covered through monosy ...201428539788
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
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
epidemiological characteristics of human and animal rabies in azerbaijan.the caucasus is a region of geopolitical importance, in the gateway between europe and asia. this geographical location makes the region equally important in the epidemiology and control of transboundary infectious diseases such as rabies. azerbaijan is the largest country in the caucasus, and although rabies is notifiable and considered endemic, there is little information on the burden of human and animal rabies. here, we describe a cross-disciplinary international collaboration aimed at impro ...201524845953
neurogenic cardiomyopathy in rabbits with experimentally induced rabies.cardiomyopathies have been rarely described in rabbits. here we report myocardial necrosis of the ventricular wall in rabbits with experimentally induced rabies. myocardial lesions were found only in rabbits with brain lesions, and the severity of the cardiac lesions was proportional to that of the brain lesions. neither the frequency nor the cumulative dose of anesthesia was related to the incidence or the severity of the myocardial lesions. the myocardial lesions were characterized by degenera ...201525047229
dogs entering the united states from rabies-endemic countries, 2011-2012.international dog imports pose a risk because of the potential movement of disease agents, including the canine rabies virus variant which has been eliminated from the united states since 2007. us regulations require a rabies vaccination certificate for dogs arriving from rabies-endemic countries, but permit the importation of dogs that have not been adequately immunized against rabies, provided that the dogs are confined under conditions that restrict their contact with humans and other animals ...201525244531
human rabies post-exposure prophylaxis and animal rabies in ontario, canada, 2001-2012.in ontario, canada, the implementation of an annual rabies control programme in wildlife that began in 1989 resulted in a marked, steady decrease in the number of animal rabies cases. the number of animal rabies cases decreased from 1870 in 1989 to 183 in 2000 (nunan et al., 2002 emerg infect dis 8, 214). in our study period, the number of animal rabies cases continued to decrease from 210 in 2001 to 28 in 2012. the marked decrease in animal rabies cases since 1989 has resulted in a decrease in ...201525244148
recommendations on vaccination for asian small animal practitioners: a report of the wsava vaccination guidelines group.in 2012 and 2013, the world small animal veterinary association (wsava) vaccination guidelines group (vgg) undertook fact-finding visits to several asian countries, with a view to developing advice for small companion animal practitioners in asia related to the administration of vaccines to dogs and cats. the vgg met with numerous first opinion practitioners, small animal association leaders, academic veterinarians, government regulators and industry representatives and gathered further informat ...201525291304
expression of interferon gamma by a recombinant rabies virus strongly attenuates the pathogenicity of the virus via induction of type i interferon.previous animal model experiments have shown a correlation between interferon gamma (ifn-γ) expression and both survival from infection with attenuated rabies virus (rabv) and reduction of neurological sequelae. therefore, we hypothesized that rapid production of murine ifn-γ by the rabies virus itself would induce a more robust antiviral response than would occur naturally in mice. to test this hypothesis, we used reverse engineering to clone the mouse ifn-γ gene into a pathogenic rabies virus ...201525320312
antigen detection, rabies virus isolation, and q-pcr in the quantification of viral load in a natural infection of the north american beaver (castor canadensis).all mammals are believed susceptible to rabies virus infection, yet transmission from nonreservoir hosts to humans is uncommon. however, interactions between nonreservoir hosts and humans occur frequently and risk of exposure increases where rabies is enzootic. we describe rabies and apparent pantropism of rabies virus in a beaver (castor canadensis).201525380356
culturing drosophila melanogaster (s2) in a chemostat.insect cells are used for the expression of complex proteins in products such as vaccines and biopharmaceuticals. physiology of a drosophila melanogaster (lineage s2), transfected to stably express rabies virus glycoprotein (rvgp), was studied in batch culture and in a chemostat with serum-free medium. in batch mode, the system reached 3 × 10(7) cells ml(-1) with specific growth rate of 1.5 d(-1) with rvgp at 2.50 µg l(-1). when operated continuously, three well-defined steady states were achiev ...201525367803
rabies vaccines: where do we stand, where are we heading?rabies being the most lethal zoonotic, vaccine-preventable viral disease with worldwide distribution of reservoir wild animals presents unique challenges for its diagnosis, management and control. although vaccines available are highly effective, which had played the key role in controlling rabies in north america, western europe and in a number of asian and latin american countries, the requirement of multiple doses along with boosters, associated cost to reduce the incidence in wild animals an ...201525348036
focal adhesion kinase is involved in rabies virus infection through its interaction with viral phosphoprotein p.the rabies virus (rabv) phosphoprotein p is a multifunctional protein: it plays an essential role in viral transcription and replication, and in addition, rabv p has been identified as an interferon antagonist. here, a yeast two-hybrid screen revealed that rabv p interacts with the focal adhesion kinase (fak). the binding involved the 106-to-131 domain, corresponding to the dimerization domain of p and the c-terminal domain of fak containing the proline-rich domains prr2 and prr3. the p-fak inte ...201525410852
genetic characterisation of the rabies virus vaccine strains used for oral immunization of foxes in poland to estimate the effectiveness of vaccination.the main reservoir of rabies virus in poland has been the red fox. to control rabies in wildlife, oral immunization of foxes was introduced in 1993. the vaccine is effective when it confers immunity against the virus circulating in the environment. to assess the above issue, a study of the molecular characteristics of 570-bp fragments of the n and g genes of vaccine strains sad b19 and sad bern against street virus strains was performed. the results confirmed the similarity of the vaccine strain ...201525408374
virology, immunology and pathology of human rabies during treatment.rabies is an acute fatal encephalitis caused by all members of the lyssavirus genus. the first human rabies survivor without benefit of prior vaccination was reported from milwaukee in 2005. we report a second unvaccinated patient who showed early recovery from rabies and then died accidentally during convalescence, providing an unparalleled opportunity to examine the histopathology as well as immune and virological correlates of early recovery from human rabies.201525405805
identification of a role for nucleolin in rabies virus infection.rabies virus replicates in the cytoplasm of host cells, but rabies virus phosphoprotein (p-protein) undergoes active nucleocytoplasmic trafficking. here we show that the largely nuclear p-protein isoform p3 can localize to nucleoli and forms specific interactions with nucleolin. importantly, depletion of nucleolin expression inhibits viral protein expression and infectious virus production by infected cells. this provides the first evidence that lyssaviruses interact with nucleolin and that nucl ...201525428867
multiple lesions by vampire bat bites in a patient in niterói, brazil - case report.over the last few centuries, the expansion of urbanization brought bats closer to urbanized areas, increasing the risk of accidents by bat bites. the morphology of bat bites can be varied, usually having an elliptical shape, about 0.5 cm along its greatest length, and the characteristic corkscrew bite pattern. the authors present the case of a patient who was repeatedly bitten by vampire bats for two months. a polymerase chain reaction was performed in the cutaneous nerves at the base of the hai ...201524770518
community survey of rabies knowledge and exposure to bats in homes - sumter county, south carolina, usa.subsequent to a human rabies death in sumter county, south carolina, we assessed the frequency of exposures to bats in homes and citizens' rabies knowledge. a self-administered survey was mailed to 6033 randomly selected sumter county addresses. the survey inquired about household exposures to bats and respondents' rabies knowledge. surveys were returned by mail for descriptive analysis. of 597 respondents, 3.5% (21/597) reported having bats living in (2.8% or 17/597) or entering their homes (2. ...201524815566
inhibition of spring viraemia of carp virus replication in an epithelioma papulosum cyprini cell line by rnai.spring viraemia of carp virus (svcv) is an aetiological agent of a serious disease affecting carp farms in europe and is a member of the rhabdoviridae family of viruses. the genome of svcv codes for five proteins: nucleoprotein (n), phosphoprotein (p), matrix protein (m), glycoprotein (g) and rna-dependent rna polymerase (l). rna-mediated interference (rnai) by small interfering rnas (sirnas) is a powerful tool to inhibit gene transcription and is used to study genes important for viral replicat ...201524460815
first isolation of a rabid bat infected with european bat lyssavirus in luxembourg.rabid bats are regularly reported in europe, especially in countries that have implemented a bat surveillance network. in may 2013, bat rabies was evidenced for the first time in luxembourg (southern city of differdange). the rabies virus, an eblv-1b strain, was diagnosed in a serotine bat that bit a 29-year-old male person while he was asleep. the man received rapidly a post-exposure rabv treatment and was put under strict medical supervision.201524373212
parallel pathways from motor and somatosensory cortex for controlling whisker movements in mice.mice can gather tactile sensory information by actively moving their whiskers to palpate objects in their immediate surroundings. whisker sensory perception therefore requires integration of sensory and motor information, which occurs prominently in the neocortex. the signalling pathways from the neocortex for controlling whisker movements are currently poorly understood in mice. here, we delineate two pathways, one originating from primary whisker somatosensory cortex (ws1) and the other from w ...201525476605
the inability of wild-type rabies virus to activate dendritic cells is dependent on the glycoprotein and correlates with its low level of the de novo-synthesized leader rna.dendritic cells (dcs) are the most efficient antigen-presenting cells, playing a key role in the adaptive immune responses to viral infections. our studies demonstrate that wild-type (wt) rabies virus (rabv) does not activate dcs. adoptive transfer of dcs primed with wt rabv did not activate dcs, stimulate virus neutralizing antibodies (vna), or protect recipients against challenge. however, adoptive transfer of dcs primed with laboratory-attenuated rabv resulted in dc activation, production of ...201525473057
antibody response of cattle to vaccination with commercial modified live rabies vaccines in guatemala.vampire bat rabies is a public and animal health concern throughout latin america. as part of an ecological study of vampire bat depredation on cattle in southern guatemala, we conducted a vaccine seroconversion study among three dairy farms. the main objectives of this cross sectional and cohort study were to understand factors associated with bat bites among cattle, to determine whether unvaccinated cattle had evidence of rabies virus exposure and evaluate whether exposure was related to bat b ...201525466762
pre- and post-exposure safety and efficacy of attenuated rabies virus vaccines are enhanced by their expression of ifnγ.consistent with evidence of a strong correlation between interferon gamma (ifnγ) production and rabies virus (rabv) clearance from the cns, we recently demonstrated that engineering a pathogenic rabv to express ifnγ highly attenuates the virus. reasoning that ifnγ expression by rabv vaccines would enhance their safety and efficacy, we reverse-engineered two proven vaccine vectors, gas and gasgas, to express murine ifnγ. mortality and morbidity were monitored during suckling mice infection, immun ...201525463615
enhanced bbb permeability of osmotically active poly(mannitol-co-pei) modified with rabies virus glycoprotein via selective stimulation of caveolar endocytosis for rnai therapeutics in alzheimer's disease.rna interference (rnai) holds one of the promising tools for alzheimer's disease (ad) treatment by directly arresting the causative genes. for successful rnai therapeutics for ad, limited access of therapeutic genes to the brain needs to be overcome by developing sirna delivery system that could cross the blood-brain barrier (bbb). here, we report a non-viral vector, rabies virus glycoprotein (rvg)-modified poly(mannitol-co-pei) gene transporter (pmt), r-peg-pmt. the rvg ligand directed the pmt/ ...201525457984
cellular immune response following pre-exposure and postexposure rabies vaccination by intradermal and intramuscular routes.immunization against rabies in humans induces protective neutralizing antibodies; however, the induction of type 1 or type 2 cytokine mediated cellular immune responses following rabies vaccination is not understood. hence, the present study investigated cellular cytokine responses in vaccinated individuals.201525649188
establishing conditions for the storage and elution of rabies virus rna using fta(®) cards.the flinders technology associates filter paper cards (fta(®) cards) can be used to store nucleic acid from various samples and are easily portable. however, rna is physicochemically unstable compared with dna, and appropriate methods have not been established for storage and extraction of rna from fta(®) cards. the present study investigated the optimum conditions for storage and elution of viral rna (vrna) using rabies virus (rabv) applied to fta(®) cards. when te buffer was used, the elution ...201525648208
phylogeography of the current rabies viruses in indonesia.rabies is a major fatal zoonotic disease in indonesia. this study was conducted to determine the recent dynamics of rabies virus (rabv) in various areas and animal species throughout indonesia. a total of 27 brain samples collected from rabid animals of various species in bali, sumatra, kalimantan, sulawesi, java, and flores in 2008 to 2010 were investigated. the cdna of the nucleoprotein gene from each sample was generated and amplified by one-step reverse transcription-pcr, after which the pro ...201525643792
comparison of immunochromatographic diagnostic test with hheminested reverse transcriptase polymerase chain reaction for detection of rabies virus from brain samples of various species.detection of rabies is a cause of serious concern in developing countries, where dearth of highly equipped laboratories and trained personnel to handle sophisticated investigations is felt. the availability of a diagnostic kit, which can be used in the field, is essential for diagnosis and control programs as well as for epidemiological surveillance of the prevalence of the disease. this study was planned to evaluate anigen rabies ag test kit for its efficacy to be used for rapid diagnosis of ra ...201527047061
use of uniform designs in combination with neural networks for viral infection process development.this work aimed to compare the predictive capacity of empirical models, based on the uniform design utilization combined to artificial neural networks with respect to classical factorial designs in bioprocess, using as example the rabies virus replication in bhk-21 cells. the viral infection process parameters under study were temperature (34°c, 37°c), multiplicity of infection (0.04, 0.07, 0.1), times of infection, and harvest (24, 48, 72 hours) and the monitored output parameter was viral prod ...201525627917
rabies surveillance in bats in northwestern state of são paulo.introduction rabies is an important zoonosis that occurs in mammals, with bats acting as lyssavirus reservoirs in urban, rural and natural areas. rabies cases in bats have been recorded primarily in urban areas in northwestern state of são paulo since 1998. this study investigated the circulation of rabies virus by seeking to identify the virus in the brain in several species of bats in this region and by measuring rabies-virus neutralizing antibody levels in the hematophagous bat desmodus rotun ...201525626649
characterization of a virulent dog-originated rabies virus affecting more than twenty fallow deer (dama dama) in inner mongolia, china.rabies has emerged as a serious problem in the most recent years in northern china. a rabies virus (rabv) isolate, imdrv-13, was recovered from brain samples of dog-bitten rabid fallow deer (dama dama) in a farm in hohhot, inner mongolia. we tested the susceptibility of mouse neuroblastoma (mna) cells and bsr cells as well as that of adult mice to imdrv-13. the isolate was found to be a virulent isolate with an equivalent pathogenicity index (0.12) and a slight lower neurotropism index (1.07) co ...201525614955
postgenomics biomarkers for rabies—the next decade of proteomics.rabies is one of the oldest diseases known to mankind. the pathogenic mechanisms by which rabies virus infection leads to development of neurological disease and death are still poorly understood. analysis of rabies-infected proteomes may help identify novel biomarkers for antemortem diagnosis of the disease and target molecules for therapeutic intervention. this article offers a literature synthesis and critique of the differentially expressed proteins that have been previously reported from va ...201525611201
knowledge, attitudes and practices regarding rabies and exposure to bats in two rural communities in guatemala.rabies is a fatal encephalitis caused by rabies virus, of the genus lyssavirus. the principal reservoir for rabies in latin america is the common vampire bat (desmodus rotundus), which feeds routinely on the blood of cattle, and when livestock are scarce, may prey on other mammals, including humans. although rabies is endemic in common vampire bat populations in guatemala, there is limited research on the extent of exposure to bats among human populations living near bat refuges.201525576098
a preliminary study of recombinant human interferon-α-2a activity against rabies virus in murine model.rabies remains an important public health problem in the world due to uncontrolled enzootic rabies. although rabies associated fatalities may be prevented with timely immunoprophylaxis, but till date a therapeutic molecule has remained elusive. we investigated the role of rhuifn α-2a in murine model challenged with rabies virus. titre of 10(4.25) ld50/0.03 ml of 10% w/v rv cvs stock suspension were obtained. based on 1ld50 titre, challenge dose of 50 ld 50 was administered along with rhuifn α-2a ...201525560017
neuroepithelial circuit formed by innervation of sensory enteroendocrine cells.satiety and other core physiological functions are modulated by sensory signals arising from the surface of the gut. luminal nutrients and bacteria stimulate epithelial biosensors called enteroendocrine cells. despite being electrically excitable, enteroendocrine cells are generally thought to communicate indirectly with nerves through hormone secretion and not through direct cell-nerve contact. however, we recently uncovered in intestinal enteroendocrine cells a cytoplasmic process that we name ...201525555217
lymph node but not intradermal injection site macrophages are critical for germinal center formation and antibody responses to rabies vaccination.replication-deficient rabies virus (rabv)-based vaccines induce rapid and potent antibody responses via t cell-independent and t cell-dependent mechanisms. to further investigate early events in vaccine-induced antibody responses against rabv infections, we studied the role of macrophages as mediators of rabv-based vaccine immunogenicity. in this report, we show that a recombinant matrix gene-deleted rabv-based vaccine (rrabv-δm) infects and activates primary murine macrophages in vitro. immuniz ...201525540370
cell-penetrating and neurotargeting dendritic sirna nanostructures.we report the development of dendritic sirna nanostructures that are able to penetrate even difficult to transfect cells such as neurons with the help of a special receptor ligand. the nanoparticles elicit strong sirna responses, despite the dendritic structure. an sirna dendrimer directed against the crucial rabies virus (rabv) nucleoprotein (n protein) and phosphoprotein (p protein) allowed the suppression of the virus titer in neurons below the detection limit. the cell-penetrating sirna dend ...201525522332
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
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
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
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
evaluation of rapid neutralizing antibody detection test against rabies virus in human sera.rapid and easy determination of protective neutralization antibody (nab) against rabies in the field is very important for an early and effective response to rabies in both animal and human health sectors. the rapid neutralizing antibody detection test (rapina), first developed in 2009 and then improved in 2012, is a quick test allowing detection of 0.5 iu/ml antibodies in human and animal sera or plasma. this study aimed to assess the rapina test by comparison with rapid focus fluorescence inhi ...201526060424
resampling method for applying density-dependent habitat selection theory to wildlife surveys.isodar theory can be used to evaluate fitness consequences of density-dependent habitat selection by animals. a typical habitat isodar is a regression curve plotting competitor densities in two adjacent habitats when individual fitness is equal. despite the increasing use of habitat isodars, their application remains largely limited to areas composed of pairs of adjacent habitats that are defined a priori. we developed a resampling method that uses data from wildlife surveys to build isodars in ...201526042998
cattle rabies vaccination--a longitudinal study of rabies antibody titres in an israeli dairy herd.in contrast to many regions of the world where rabies is endemic in terrestrial wildlife species, wildlife rabies has been controlled in israel by oral rabies vaccination programs, but canine rabies is re-emerging in the northern area of the golan heights. from 2009 to 2014 there were 208 animal rabies cases in israel; 96 (46%) were considered introduced primary cases in dogs, triggering 112 secondary cases. one third (37/112) of the secondary cases were in cattle. rabies vaccination is voluntar ...201526032721
effects of g-gene deletion and replacement on rabies virus vector gene expression.the glycoprotein-gene (g gene) -deleted rabies virus (rv) vector is a powerful tool to examine the function and structure of neural circuits. we previously reported that the deletion of the g gene enhances the transgene expression level of the rv vector. however, the mechanism of this enhancement remains to be clarified. we presume that there are two possible factors for this enhancement. the first factor is the glycoprotein of rv, which shows cytotoxicity; thus, may cause a dysfunction in the t ...201526023771
modeling the geographic spread of rabies in china.in order to investigate how the movement of dogs affects the geographically inter-provincial spread of rabies in mainland china, we propose a multi-patch model to describe the transmission dynamics of rabies between dogs and humans, in which each province is regarded as a patch. in each patch the submodel consists of susceptible, exposed, infectious, and vaccinated subpopulations of both dogs and humans and describes the spread of rabies among dogs and from infectious dogs to humans. the existen ...201526020234
segmental organization of vestibulospinal inputs to spinal interneurons mediating crossed activation of thoracolumbar motoneurons in the neonatal mouse.vestibulospinal pathways activate contralateral motoneurons (mns) in the thoracolumbar spinal cord of the neonatal mouse exclusively via axons descending ipsilaterally from the vestibular nuclei via the lateral vestibulospinal tract (lvst; kasumacic et al., 2010). here we investigate how transmission from the lvst to contralateral mns is mediated by descending commissural interneurons (dcins) in different spinal segments. we test the polysynaptic nature of this crossed projection by assessing lv ...201526019332
utility of forensic detection of rabies virus in decomposed exhumed dog carcasses.this report describes four suspected rabies cases in domestic dogs that were involved inhuman exposures. in all these cases, the animals were buried for substantial times beforerabies testing was performed. animal rabies is endemic in south africa and domestic dogsare the main vector for transmission to humans. diagnosis of rabies in humans is complicated,and diagnosis in the animal vector can provide circumstantial evidence to support clinicaldiagnosis of rabies in humans. the gold standard dia ...201526016574
monosynaptic tracing using modified rabies virus reveals early and extensive circuit integration of human embryonic stem cell-derived neurons.human embryonic stem cell (hesc)-derived dopamine neurons are currently moving toward clinical use for parkinson's disease (pd). however, the timing and extent at which stem cell-derived neurons functionally integrate into existing host neural circuitry after transplantation remain largely unknown. in this study, we use modified rabies virus to trace afferent and efferent connectivity of transplanted hesc-derived neurons in a rat model of pd and report that grafted human neurons integrate into t ...201526004633
reverse genetics of rabies virus: new strategies to attenuate virus virulence for vaccine development.rabies is an ancient neurological disease that is almost invariably fatal once the clinical symptoms develop. currently, prompt wound cleansing after exposing to a potentially rabid animal and vaccination using rabies vaccine combined with administration of rabies immune globulin are the only effective methods for post-exposure prophylaxis against rabies. reverse genetic technique is a novel approach to investigate the function of a specific gene by analyzing the phenotypic effects through direc ...201525994916
fluorescent-protein stabilization and high-resolution imaging of cleared, intact mouse brains.in order to observe and quantify long-range neuronal connections in intact mouse brain by light microscopy, it is first necessary to clear the brain, thus suppressing refractive-index variations. here we describe a method that clears the brain and preserves the signal from proteinaceous fluorophores using a ph-adjusted non-aqueous index-matching medium. successful clearing is enabled through the use of either 1-propanol or tert-butanol during dehydration whilst maintaining a basic ph. we show th ...201525993380
atypical rabies encephalitis in a six-year-old boy: clinical, radiological, and laboratory findings.a 6-year-old boy from india developed an atypical form of rabies following a stray dog bite and as a consequence of not receiving the standard world health organization recommended post-exposure prophylaxis for category iii wounds. serial rising rabies virus neutralizing antibody titres in serum and cerebrospinal fluid by rapid fluorescent focus inhibition test helped confirm the diagnosis of rabies. the child has survived for 4 months since the onset of illness, albeit with neurological sequela ...201525975650
deciphering the unconventional peptide binding to the pdz domain of mast2.phosphatase and tensin homologue (pten) and microtubule-associated serine threonine kinase 2 (mast2) are key negative regulators of survival pathways in neuronal cells. the two proteins interact via the pdz (psd-95, dlg1, zo-1) domain of mast2 (mast2-pdz). during infection by rabies virus, the viral glycoprotein competes with pten for interaction with mast2-pdz and promotes neuronal survival. the c-terminal pdz-binding motifs (pbms) of the two proteins bind similarly to mast2-pdz through an unco ...201525942057
differential organization of cortical inputs to striatal projection neurons of the matrix compartment in rats.in prior studies, we described the differential organization of corticostriatal and thalamostriatal inputs to the spines of direct pathway (dspns) and indirect pathway striatal projection neurons (ispns) of the matrix compartment. in the present electron microscopic (em) analysis, we have refined understanding of the relative amounts of cortical axospinous vs. axodendritic input to the two types of spns. of note, we found that individual dspns receive about twice as many axospinous synaptic term ...201525926776
first report on the efficiency of oral vaccination of foxes against rabies in serbia.rabies is one of the oldest known zoonotic diseases that has significant impact on public health, but still remains neglected in serbia. rabies virus can infect humans and other mammals and causes inflammation of the brain associated with encephalomyelitis and neurological symptoms. in 2010, veterinary directorate (national competent authority for animal health in serbia) has started multi-annual project of oral rabies vaccination of foxes and other wild carnivores (e.g. jackals), as support of ...201525903646
extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting.extracellular vesicles (evs) have emerged as important mediators of intercellular communication in a diverse range of biological processes. for future therapeutic applications and for ev biology research in general, understanding the in vivo fate of evs is of utmost importance. here we studied biodistribution of evs in mice after systemic delivery. evs were isolated from 3 different mouse cell sources, including dendritic cells (dcs) derived from bone marrow, and labelled with a near-infrared li ...201525899407
whole-brain mapping of the direct inputs and axonal projections of pomc and agrp neurons.pro-opiomelanocortin (pomc) neurons in the arcuate nucleus (arc) of the hypothalamus and nucleus tractus solitarius (nts) of the brainstem play important roles in suppressing food intake and maintaining energy homeostasis. previous tract-tracing studies have revealed the axonal connection patterns of these two brain areas, but the intermingling of pomc neurons with other neuron types has made it challenging to precisely identify the inputs and outputs of pomc neurons. in this study, we used the ...201525870542
immunogenic virus-like particles continuously expressed in mammalian cells as a veterinary rabies vaccine candidate.rabies is one of the most lethal infectious diseases in the world, with a mortality approaching 100%. there are between 60,000 and 70,000 reported annual deaths, but this is probably an underestimation. despite the fact that there are vaccines available for rabies, there is a real need of developing more efficacious and cheaper vaccines. this is particularly true for veterinary vaccines because dogs are still the main vector for rabies transmission to human beings. in a previous work, we describ ...201525869890
clinical management and humoral immune responses to rabies post-exposure prophylaxis among three patients who received solid organs from a donor with rabies.the rabies virus causes a fatal encephalitis and can be transmitted through organ transplantation. in 2013, a man developed rabies 18 months after receiving a kidney from a donor with rabies, who was not known to have been infected when the organs were procured. three additional persons who received organs from the same donor (liver, kidney, heart), all of whom were not vaccinated for rabies before transplantation, received rabies post-exposure prophylaxis (pep) with rabies immune globulin and 5 ...201525851103
a recombinant rabies virus expressing a phosphoprotein-egfp fusion is rescued and applied to the rapid virus neutralization antibody assay.rabies remains a worldwide concern, and dogs are a major vector for rabies virus (rabv) transmission. vaccination is used in china to control the spread of rabies in dogs, a practice which necessitates effective, efficient, and high-throughput methods to confirm vaccination. the current rapid fluorescent focus inhibition test (rffit) method to measure virus-neutralizing antibody titers in the serum involves multiple steps, and more efficient methods are needed to match the increasing demand for ...201525845623
a comparative approach between heterologous prime-boost vaccination strategy and dna vaccinations for rabies.rabies is a widespread neurological zoonotic disease causing significant mortality rates, especially in developing countries. although a vaccine for rabies is available, its production and scheduling are costly in such countries. advances in recombinant dna technology have made it a good candidate for an affordable vaccine. among the proteins of rabies virus, the glycoprotein (rvg) has been the major target for new vaccine development which plays the principal role in providing complete protecti ...201525841942
a new strategy for specific imaging of neural cells based on peptide-conjugated gold nanoclusters.despite the significant progress in molecular imaging technologies that has been made in recent years, the specific detection of neural cells still remains challenging. here, we suggest the use of gold nanoclusters (auncs) modified with a brain-targeting peptide as a potential imaging candidate for detecting neural cells in vitro and in mice. auncs of less than 10 nm (dynamic light scattering analysis) were first prepared using the "green" synthetic approach, and then a targeting peptide, rabies ...201525834429
lentiviral vectors for retrograde delivery of recombinases and transactivators.lentiviral vectors pseudotyped with the rabies virus (rv) envelope glycoprotein efficiently infect via axon terminals to stably deliver transgenes to distant neurons projecting to an injection site, but the resulting expression levels are too low and variable for most neuroscientific applications. if used to deliver recombinases or transactivators, however, lentiviral vectors are excellent means of targeting projection neurons when used in reporter mice or in combination with a second virus to e ...201525834255
whole-brain mapping of inputs to projection neurons and cholinergic interneurons in the dorsal striatum.the dorsal striatum integrates inputs from multiple brain areas to coordinate voluntary movements, associative plasticity, and reinforcement learning. its projection neurons consist of the gabaergic medium spiny neurons (msns) that express dopamine receptor type 1 (d1) or dopamine receptor type 2 (d2). cholinergic interneurons account for a small portion of striatal neuron populations, but they play important roles in striatal functions by synapsing onto the msns and other local interneurons. by ...201525830919
molecular epidemiology of rabies viruses circulating in two rabies endemic provinces of laos, 2011-2012: regional diversity in southeast asia.although rabies is endemic in laos, genetic characterization of the viruses in this country is limited. there are growing concerns that development in the region may have increased transport of dog through laos for regional dog meat consumption, and that this may cause spillover of the viruses from dogs brought here from other countries. this study was therefore undertaken to evaluate the current rabies situation and the genetic characteristics of rabies viruses currently circulating in laos.201525825907
novel approaches to the prevention and treatment of rabies.rabies is a highly lethal disease caused by the neurotropic rabies virus (rabv), and it remains an important public health problem globally. effective vaccines have been developed for pre- and post-exposure prophylaxis (pep). pep is only effective if it is initiated promptly after recognizing exposure. once neurological symptoms develop, however, it is widely accepted that there is no effective treatment available. recent studies indicate that the presence of rabv-specific immunity (i.e. virus n ...201527891529
complete genomic sequence of rabies virus from an ethiopian wolf.ethiopian wolves are the rarest canid in the world, with only 500 found in the ethiopian highlands. rabies poses the most immediate threat to their survival, causing epizootic cycles of mass mortality. the complete genome sequence of a rabies virus (rabv) derived from an ethiopian wolf during the most recent epizootic is reported here.201525814597
rabies vaccine preserved by vaporization is thermostable and immunogenic.a rabies vaccine that is thermostable over a range of ambient environmental temperatures would be highly advantageous, especially for tropical regions with challenging cold-chain storage where canine rabies remains enzootic resulting in preventable human mortality. live attenuated rabies virus (rabv) strain erag333 (r333e) was preserved by vaporization (pbv) in a dry, stable foam. rabv stabilized using this process remains viable for at least 23 months at 22°c, 15 months at 37°c, and 3h at 80°c. ...201525812841
complex epidemiology of a zoonotic disease in a culturally diverse region: phylogeography of rabies virus in the middle east.the middle east is a culturally and politically diverse region at the gateway between europe, africa and asia. spatial dynamics of the fatal zoonotic disease rabies among countries of the middle east and surrounding regions is poorly understood. an improved understanding of virus distribution is necessary to direct control methods. previous studies have suggested regular trans-boundary movement, but have been unable to infer direction. here we address these issues, by investigating the evolution ...201525811659
animal-associated exposure to rabies virus among travelers, 1997-2012.among travelers, rabies cases are rare, but animal bites are relatively common. to determine which travelers are at highest risk for rabies, we studied 2,697 travelers receiving care for animal-related exposures and requiring rabies postexposure prophylaxis at geosentinel clinics during 1997-2012. no specific demographic characteristics differentiated these travelers from other travelers seeking medical care, making it challenging to identify travelers who might benefit from reinforced pretravel ...201525811076
chimeric rabies virus-like particles containing membrane-anchored gm-csf enhances the immune response against rabies virus.rabies remains an important public health threat in most developing countries. to develop a more effective and safe vaccine against rabies, we have constructed a chimeric rabies virus-like particle (vlp), which containing glycoprotein (g) and matrix protein (m) of rabies virus (rabv) evelyn-rokitnicki-abelseth (era) strain, and membrane-anchored granulocyte-macrophage colony-stimulating factor (gm-csf), and it was named of evlp-g. the immunogenicity and protective efficacy of evlp-g against rabv ...201525768031
association between rabv g proteins transported from the perinuclear space to the cell surface membrane and n-glycosylation of the sequon asn(204).in this study, g proteins of the rabies virus (rabv) kyoto strain were detected in the cytoplasm but not distributed at the cell membrane of mouse neuroblastoma (mna) cells. g proteins of cvs-26 were detected in both the cell membrane and perinuclear space of mna cells. we found that n-glycosylation of street rabv g protein by the insertion of the sequon asn(204) induced the transfer of rabv g proteins to the cell surface membrane. fixed rabv budding from the plasma membrane has been found to de ...201525766612
high-throughput differentiation and screening of a library of mutant stem cell clones defines new host-based genes involved in rabies virus infection.we used a genomic library of mutant murine embryonic stem cells (escs) and report the methodology required to simultaneously culture, differentiate, and screen more than 3,200 heterozygous mutant clones to identify host-based genes involved in both sensitivity and resistance to rabies virus infection. established neuronal differentiation protocols were miniaturized such that many clones could be handled simultaneously, and molecular markers were used to show that the resultant cultures were pan- ...201525752821
strategies to interfere with pdz-mediated interactions in neurons: what we can learn from the rabies virus.pdz (psd-95/dlg/zo-1) domains play a major role in neuronal homeostasis in which they act as scaffold domains regulating cellular trafficking, self-association and catalytic activity of essential proteins such as kinases and phosphatases. because of their central role in cell signaling, cellular pdz-containing proteins are preferential targets of viruses to hijack cellular function to their advantage. here, we describe how the viral g protein of the rabies virus specifically targets the pdz doma ...201525748547
using rabies virus vaccine strain srv9 as viral vector to express exogenous gene.rabies virus (rabv) can cause a fatal neurological disease in human and animals, and vaccines were generally applied for the immunoprophylaxis of rabies. here, a recombinant viral vector carrying the exogenous gene expression component between phosphoprotein (p) and matrix protein (m) genes of rabv was constructed based on the vaccine strain srv9 used in china. to develop a reverse genetic system, the full-length cdna plasmids of srv9 were constructed using the eukaryotic expression vector pci o ...201525724175
synthesis and characterization of rabies virus glycoprotein-tagged amphiphilic cyclodextrins for sirna delivery in human glioblastoma cells: in vitro analysis.in man brain cancer is an aggressive, malignant form of tumour, it is highly infiltrative in nature, is associated with cellular heterogeneity and affects cerebral hemispheres of the brain. current drug therapies are inadequate and an unmet clinical need exists to develop new improved therapeutics. the ability to silence genes associated with disease progression by using short interfering rna (sirna) presents the potential to develop safe and effective therapies. in this work, in order to protec ...201525703259
transient expression of rabies virus g-glycoprotein using bhk-21 cells cultured in suspension.to assess the expression of rabies virus g-glycoprotein (rvgp) expression using semliki forest virus as a vector in combination with bhk-21 cells cultured in suspension.201525700821
rabies virus phosphoprotein interacts with mitochondrial complex i and induces mitochondrial dysfunction and oxidative stress.our previous studies in an experimental model of rabies showed neuronal process degeneration in association with severe clinical disease. cultured adult rodent dorsal root ganglion neurons infected with challenge virus standard (cvs)-11 strain of rabies virus (rabv) showed axonal swellings and reduced axonal growth with evidence of oxidative stress. we have shown that cvs infection alters a variety of mitochondrial parameters and increases reactive oxygen species (ros) production and mitochondri ...201525698500
comparative study on the immunogenicity and safety of a purified chick embryo cell rabies vaccine (pcecv) administered according to two different simulated post exposure intramuscular regimens (zagreb versus essen).despite availability of effective rabies vaccines, india has the highest global mortality rate for rabies. low socio-economic communities are most affected due to lack of awareness of the disease and poor compliance to post-exposure prophylactic regimens. currently, the only approved intramuscular regimen for post-exposure prophylaxis (pep) against rabies in india is the essen regimen, which consists of 5 injections administered over 5 separate days in a period of one month. the high number of d ...201525692792
immunogenicity and safety of purified chick-embryo cell rabies vaccine under zagreb 2-1-1 or 5-dose essen regimen in chinese children 6 to 17 years old and adults over 50 years: a randomized open-label study.the aim of this phase iiib, open-label, randomized study was to demonstrate the non-inferiority of immune responses and to assess the safety of a purified chick-embryo cell rabies vaccine (pcecv) in healthy chinese children (6 to 17 years) and older adults (≥51 years) following 2 alternative intramuscular (im) simulated post-exposure prophylaxis (pep) regimens: 4-dose zagreb or 5-dose essen regimen. serum samples were collected prior to vaccination on days 1 and 15 and on day 43 to assess immune ...201525692350
polyion complex micelles composed of pegylated polyasparthydrazide derivatives for sirna delivery to the brain.in order to achieve efficient sirna delivery to the brain, we designed a novel polyion complex (pic) micelles composed of rabies virus glycoprotein (rvg) peptide tagged pegylated polyasparthydrazide (pahy) derivatives. the synthesized derivatives were characterized using (1)h nmr. the pic micelles were formed by electrostatic attraction between the polymer and sirna. then the micelles were decorated with rvg using peg as a linker. the physiochemical properties of micelles, such as gel retardatio ...201525689522
vesicular stomatitis virus enables gene transfer and transsynaptic tracing in a wide range of organisms.current limitations in technology have prevented an extensive analysis of the connections among neurons, particularly within nonmammalian organisms. we developed a transsynaptic viral tracer originally for use in mice, and then tested its utility in a broader range of organisms. by engineering the vesicular stomatitis virus (vsv) to encode a fluorophore and either the rabies virus glycoprotein (rabv-g) or its own glycoprotein (vsv-g), we created viruses that can transsynaptically label neuronal ...201525688551
a three-year (2011-2013) surveillance on animal bites and victims vaccination in the south of khorasan-e-razavi province, iran.rabies is acute encephalitis caused by rabies virus and is transmissible between humans and warm blooded animals. the virus is belong to the family of rabdoviridae and, of lissavirus genus.201526816921
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
[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
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
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
[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
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
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
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
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
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
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
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
rabies epidemiology and control in ecuador.describe the epidemiology and the control effort for rabies in ecuador.201526493436
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
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