Publications

the global phylogeography of lyssaviruses - challenging the 'out of africa' hypothesis.	rabies virus kills tens of thousands of people globally each year, especially in resource-limited countries. yet, there are genetically- and antigenically-related lyssaviruses, all capable of causing the disease rabies, circulating globally among bats without causing conspicuous disease outbreaks. the species richness and greater genetic diversity of african lyssaviruses, along with the lack of antibody cross-reactivity among them, has led to the hypothesis that africa is the origin of lyssaviru ...	2016	28036390
role of nitric oxide in the regulation of immune responses during rabies virus infection in mice.	rabies virus (rabv) stimulates nitric oxide (no) production, which either triggers t cell differentiation or suppresses t cell function depending on its concentration. herein, we assessed the potential role of no in regulation of immune responses during rabv infection in mice model. the experimental animals were divided into four groups and 100ld50 of challenge virus standard (cvs) strain of rabv was inoculated intracerebrally on day 0 and subsequently aminoguanidine (ag; inducible nitric oxide ...	2016	28004019
the matrix protein of rabies virus binds to relap43 to modulate nf-κb-dependent gene expression related to innate immunity.	the matrix (m) protein of wild isolates of rabies virus such as tha (m-tha) was previously shown to be able to interact with relap43, a protein of the nf-κb family, and to efficiently suppress nf-κb-dependent reporter gene expression, in contrast with the vaccine strain sad. here, we analyze the mechanisms involved in relap43-m protein interaction. we demonstrate that the central part of m-tha, and the specific c-terminal region of relap43 are required for this interaction. four differences in t ...	2016	28000711
serine residues at positions 162 and 166 of the rabies virus phosphoprotein are critical for the induction of oxidative stress in rabies virus infection.	our previous work in a mouse model of experimental rabies showed neuronal process (dendrites and axons) degeneration in association with severe clinical disease. cultured adult rodent dorsal root ganglion (drg) neurons infected with the challenge virus standard-11 (cvs) 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 mitochondrial complex ...	2016	27995576
cre fused with rvg peptide mediates targeted genome editing in mouse brain cells in vivo.	cell penetrating peptides (cpps) are short peptides that can pass through cell membranes. cpps can facilitate the cellular entry of proteins, macromolecules, nanoparticles and drugs. rvg peptide (rvg hereinafter) is a 29-amino-acid cpp derived from a rabies virus glycoprotein that can cross the blood-brain barrier (bbb) and enter brain cells. however, whether rvg can be used for genome editing in the brain has not been reported. in this work, we combined rvg with cre recombinase for bacterial ex ...	2016	27983648
large-scale phylogenomic analysis reveals the complex evolutionary history of rabies virus in multiple carnivore hosts.	the natural evolution of rabies virus (rabv) provides a potent example of multiple host shifts and an important opportunity to determine the mechanisms that underpin viral emergence. using 321 genome sequences spanning an unprecedented diversity of rabv, we compared evolutionary rates and selection pressures in viruses sampled from multiple primary host shifts that occurred on various continents. two major phylogenetic groups, bat-related rabv and dog-related rabv, experiencing markedly differen ...	2016	27977811
the epidemiological importance of bats in the transmission of rabies to dogs and cats in the state of são paulo, brazil, between 2005 and 2014.	in brazil, rabies control in dogs and cats was pioneered by the state of são paulo with the adoption of the pan american health organization recommendations for prophylaxis and control, which led to a reduction in rabies cases from 1994 onwards. as a result of these measures, the rabies virus (rabv) genetic lineage associated with dogs has not been found in the state since 1998, and all the cases in domestic animals reported since then have been caused by bat-associated lineages of rabv. in the ...	2016	27863049
a comparative study of the rapina and the virus-neutralizing test (rffit) for the estimation of antirabies-neutralizing antibody levels in dog samples.	the mass vaccination of dogs against rabies is a highly rational strategy for interrupting the natural transmission of urban rabies. according to the world organization for animal health (oie) and the world health organization (who), the immunization of at least 70% of the total dog population minimizes the risk of endemic rabies. knowledge of the virus-neutralizing antibody (vna) level against the rabies virus (rabv) is required to evaluate protective immunity and vaccine coverage of dogs in th ...	2016	27863040
impact of rabies vaccination history on attainment of an adequate antibody titre among dogs tested for international travel certification, israel - 2010-2014.	rabies is endemic in wildlife or domestic carnivore populations globally. infection of domestic dogs is of particular concern in many areas. in regions where domestic animals are at risk of exposure to rabies virus, dogs should be routinely vaccinated against rabies to protect both pet and human populations. many countries require demonstration of an adequate level of serum rabies neutralizing antibodies to permit entry of dogs during international travel. we analysed rabies titres of dogs seeki ...	2016	27911041
recombinant rabies virus expressing il-21 enhances immunogenicity through activation of t follicular helper cells and germinal centre b cells.	previous studies have demonstrated that the lack of interleukin-21 (il-21) signalling could affect specific antibody induction after rabies vaccination. here, to further investigate the over-expression of il-21 on the immunogenicity of rabies virus (rabv), a recombinant rabv expressing murine il-21, designated lbnse-il21, was constructed and evaluated in a mouse model. it was found that in mice immunized with lbnse-il21, there was a substantial increase in the number of t follicular helper cells ...	2016	27902338
a presumptive case of human rabies: a rare survived case in rural ghana.	rabies remains endemic in ghana and continues to pose a major public health threat to humans and animals with a nearly 100% case fatality rate in humans. we report of a presumptive case of human rabies whose survival represents a rare occurrence in rural ghana and worldwide. lessons from this case study provide a critically needed focus in helping improve rabies surveillance and case management in ghana. we report of the survival of a 36-year-old man who developed clinical rabies after he was bi ...	2016	27891499
systems biomedicine of rabies delineates the affected signaling pathways.	the prototypical neurotropic virus, rabies, is a member of the rhabdoviridae family that causes lethal encephalomyelitis. although there have been a plethora of studies investigating the etiological mechanism of the rabies virus and many precautionary methods have been implemented to avert the disease outbreak over the last century, the disease has surprisingly no definite remedy at its late stages. the psychological symptoms and the underlying etiology, as well as the rare survival rate from ra ...	2016	27872612
optimal frequency of rabies vaccination campaigns in sub-saharan africa.	rabies causes more than 24 000 human deaths annually in sub-saharan africa. the world health organization recommends annual canine vaccination campaigns with at least 70% coverage to control the disease. while previous studies have considered optimal coverage of animal rabies vaccination, variation in the frequency of vaccination campaigns has not been explored. to evaluate the cost-effectiveness of rabies canine vaccination campaigns at varying coverage and frequency, we parametrized a rabies v ...	2016	27852799
viral infection: rabies virus causes stress.		2016	27818500
a basal ganglia circuit for evaluating action outcomes.	the basal ganglia, a group of subcortical nuclei, play a crucial role in decision-making by selecting actions and evaluating their outcomes. while much is known about the function of the basal ganglia circuitry in selection, how these nuclei contribute to outcome evaluation is less clear. here we show that neurons in the habenula-projecting globus pallidus (gph) in mice are essential for evaluating action outcomes and are regulated by a specific set of inputs from the basal ganglia. we find in a ...	2016	27652894
ineffectiveness of rabies vaccination alone for post-exposure protection against rabies infection in animal models.	most reported vaccination failures among rabies-exposed patients were due to fail to timely co-administer rabies immunoglobulin (rig). considering that such protection failure might be caused by low antigen titers in the vaccine, scientists improved antigen titers to 4.0 iu or even higher, yet the failure remained. therefore, it becomes vital to develop more efficacious vaccine against rabies. in our evaluation of a novel pika rabies vaccine, we used multiple animal models (beagles, golden hamst ...	2016	27737787
whole-brain monosynaptic afferent inputs to basal forebrain cholinergic system.	the basal forebrain cholinergic system (bfcs) robustly modulates many important behaviors, such as arousal, attention, learning and memory, through heavy projections to cortex and hippocampus. however, the presynaptic partners governing bfcs activity still remain poorly understood. here, we utilized a recently developed rabies virus-based cell-type-specific retrograde tracing system to map the whole-brain afferent inputs of the bfcs. we found that the bfcs receives inputs from multiple cortical ...	2016	27777554
visuomotor signals for reaching movements in the rostro-dorsal sector of the monkey thalamic reticular nucleus.	the thalamic reticular nucleus (trn) collects inputs from the cerebral cortex and thalamus and, in turn, sends inhibitory outputs to the thalamic relay nuclei. this unique connectivity suggests that the trn plays a pivotal role in regulating information flow through the thalamus. here, we analyzed the roles of trn neurons in visually guided reaching movements. we first used retrograde transneuronal labeling with rabies virus, and showed that the rostro-dorsal sector of the trn (trnrd) projected ...	2016	27706860
g gene-deficient single-round rabies viruses for neuronal circuit analysis.	rhabdoviruses like the neurotropic rabies virus are fully amenable to pseudotyping with homologous and heterologous membrane proteins, which is being harnessed for the study of viral envelope proteins, viral retargeting, or immunization purposes. particularly, pseudotyped delta g rabies viruses are emerging as safe and superb tools for mapping direct synaptic connections and analyzing neuronal circuits in the central and peripheral nervous system, which is a fundamental pillar of modern neurosci ...	2016	26065596
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 ...	2016	26497316
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 ...	2016	26655239
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 ...	2016	26650039
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 ...	2016	26647356
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 ...	2016	26647155
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 ...	2016	26317441
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 ...	2016	26611586
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 ...	2016	26589333
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 ...	2016	26573885
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 ...	2016	26569350
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 ...	2016	26560756
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 ...	2016	26560463
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 ...	2016	26547510
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 ...	2016	26542085
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 ...	2016	26661691
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 ...	2016	26656837
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 ...	2016	26656835
validation of a rapid rabies diagnostic tool for field surveillance in developing countries.	one root cause of the neglect of rabies is the lack of adequate diagnostic tests in the context of low income countries. a rapid, performance friendly and low cost method to detect rabies virus (rabv) in brain samples will contribute positively to surveillance and consequently to accurate data reporting, which is presently missing in the majority of rabies endemic countries.	2016	27706156
combining optogenetics and electrophysiology to analyze projection neuron circuits.	a set of methods is described for channelrhodopsin-2 (chr2)-based synaptic circuit analysis that combines photostimulation of virally transfected presynaptic neurons' axons with whole-cell electrophysiological recordings from retrogradely labeled postsynaptic neurons. the approach exploits the preserved photoexcitability of chr2-expressing axons in brain slices and can be used to assess either local or long-range functional connections. stereotaxic injections are used both to express chr2 select ...	2016	27698240
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 ...	2016	26711511
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 ...	2016	26705238
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 ...	2016	26731189
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 ...	2016	26729030
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 ...	2016	26724676
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 ...	2016	26765968
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 ...	2016	26757259
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 ...	2016	26739549
diabolical effects of rabies encephalitis.	rabies is an acute encephalomyelitis in humans and animals caused by rabies virus (rabv) infection. because the neuropathological changes are very mild in rabies, it has been assumed that neuronal dysfunction likely explains the severe clinical disease. recently, degenerative changes have been observed in neuronal processes (dendrites and axons) in experimental rabies. in vitro studies have shown evidence of oxidative stress that is caused by mitochondrial dysfunction. recent work has shown that ...	2016	25994917
altered functional connectivity networks in acallosal and socially impaired btbr mice.	agenesis of the corpus callosum (agcc) is a congenital condition associated with wide-ranging emotional and social impairments often overlapping with the diagnostic criteria for autism. mapping functional connectivity in the acallosal brain can help identify neural correlates of the deficits associated with this condition, and elucidate how congenital white matter alterations shape the topology of large-scale functional networks. by using resting-state bold functional magnetic resonance imaging ...	2016	25445840
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 ...	2016	26278996
[production of the monoclonal antibodies to the rabies virus nucleoprotein].	five hybridomas secreting monoclonal antibodies (mabs) for the nucleocapsid protein of the rabies virus were obtained through the fusion of the sp2/0 murine myeloma cells with splenocytes of balb/c mice immunized with fixed rabies virus (cvs strain). all hybridomas secret mabs of the igg class that display different specificity to the nucleocapsids of rabies and rabies-related viruses. mabs 2ell showed the specificity for the prevalent in russia rabies viruses that are similar to commercially av ...	2016	24640170
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 ...	2016	26690069
[genetic characterization of the rabies virus field isolates detected in russian federation within the period 2008-2011].	sixty-three gene n fragments of rabies virus field isolates detected within the period 2008-2011 in different regions of russian federation were sequenced. the comparison with previously tested isolates and strains has shown that newly isolated isolates can be placed into five previously described phylogenetic groups: arctic group, central russian group, eurasian group, northern european group, and caucasian group. the arctic group isolates detected in komi republic were identical to previously ...	2016	24354065
[significance of modern methods for laboratory detection of rabies agents and identification of the zoonose immunological survey].	analytical review of modern methods of the laboratory detection of rabies and findings of our research indicate high sensitivity and specificity of methods for rapid identification of rabies agents, such as elisa, reverse-transcriptase pcr for identification of the rabies virus genome, and rabies virus isolation in rat gasserian ganglion neurinoma, as well as their potential to be included into the state quality standard for early detection of rabies in animals to reduce the infection risk among ...	2016	25335412
developmental sculpting of intracortical circuits by mhc class i h2-db and h2-kb.	synapse pruning is an activity-regulated process needed for proper circuit sculpting in the developing brain. major histocompatibility class i (mhci) molecules are regulated by activity, but little is known about their role in the development of connectivity in cortex. here we show that protein for 2 mhci molecules h2-kb and h2-db is associated with synapses in the visual cortex. pyramidal neurons in mice lacking h2-kb and h2-db (kbdb ko) have more extensive cortical connectivity than normal. mo ...	2016	25316337
animal bite and rabies postexposure prophylaxis reporting--united states, 2013.	rabies virus causes a fatal encephalitis and is typically acquired through the bite of an infected mammal. rabies is preventable through administration of rabies postexposure prophylaxis (pep), but this must be balanced with the need to avoid unnecessary pep use. though not nationally notifiable, some state health departments (shds) have made animal bites and use of pep reportable within their jurisdictions.	2016	25084537
[a summary of the data about antigenic and genetic diversity of rabies virus circulating in the terrestrial mammals in russia].	the data about antigenic and molecular-genetic diversity of the rabies virus circulating in russia are reviewed. based on our studies and the literature data analysis circulation of two phylogenetic virus groups in russia was revealed: arctic and cosmopolitic. the arctic group includes the subgroups of proper arctic and arctic-like viruses; the cosmopolitic--central russian, northeastern european and steppe. it was found that the division into subgroups corresponded to the geographic distributio ...	2016	24006626
[a new principle in the selection of vaccinal rabies virus based on quantitation of the expression of g protein, a major immunogen of rabies virus].	the paper describes a new principle of the selection of the rabies virus vaccine strain era-cb20m based on quantitation of the expression of glycoprotein, a major immunogen of rabies virus. there is a correlation between the level of glycoprotein expression and that of vaccine virus attenuation. the application of the new principle for vaccine virus selection will permit a safer and more immunogenic rabies vaccine to be prepared.	2016	22905428
bat-borne rabies in latin america.	the situation of rabies in america is complex: rabies in dogs has decreased dramatically, but bats are increasingly recognized as natural reservoirs of other rabies variants. here, bat species known to be rabies-positive with different antigenic variants, are summarized in relation to bat conservation status across latin america. rabies virus is widespread in latin american bat species, 22.5%75 of bat species have been confirmed as rabies-positive. most bat species found rabies positive are clas ...	2017	25651328
[effect of free-roaming dogs culling on the control of canine rabies].	in the peruvian city of arequipa, rabid dogs have been detected since march 2015, signaling the reintroduction of the rabies virus (rv) in this previously officially-declared rabies free zone. high dog density is considered one of the causes for the continuous transmission of the rv in the outbreak in the city of arequipa, which seemingly lends support to the culling of dogs as a public health measure. however, the effectiveness of culling free-roaming dogs to control urban rabies has not been e ...	2017	28327849
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 ...	2017	26691990
phylogenetic analysis of rabies virus isolated from canids in north and northeast brazil.	cases of canine rabies continue to occur in north and northeast brazil, and the number of notifications of rabies cases in wild canids has increased as a result of the expansion of urban areas at the expense of areas with native vegetation. in light of this, we performed molecular characterization of rabies virus isolates from dogs and cerdocyon thous from various states in north and northeast brazil. in all, 102 samples from dogs (n = 56) and cerdocyon thous (n = 46) collected between 2006 and ...	2017	27671776
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 ...	2017	26423323
[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 ...	2017	26299857
rabies virus-mediated oligodendrocyte labeling reveals a single oligodendrocyte myelinates axons from distinct brain regions.	oligodendrocytes myelinate neuronal axons during development and increase conduction velocity of neuronal impulses in the central nervous system. neuronal axons extend from multiple brain regions and pass through the white matter; however, whether oligodendrocytes ensheath a particular set of axons or do so randomly within the mammalian brain remains unclear. we developed a novel method to visualize individual oligodendrocytes and axon derived from a particular brain region in mouse white matter ...	2017	27759175
morphology of visual sector thalamic reticular neurons in the macaque monkey suggests retinotopically specialized, parallel stream-mixed input to the lateral geniculate nucleus.	the thalamic reticular nucleus (trn) is a unique brain structure at the interface between the thalamus and the cortex. because the trn receives bottom-up sensory input and top-down cortical input, it could serve as an integration hub for sensory and cognitive signals. functional evidence supports broad roles for the trn in arousal, attention, and sensory selection. how specific circuits connecting the trn with sensory thalamic structures implement these functions is not known. the structural org ...	2017	27778378
the family rhabdoviridae: mono- and bipartite negative-sense rna viruses with diverse genome organization and common evolutionary origins.	the family rhabdoviridae consists of mostly enveloped, bullet-shaped or bacilliform viruses with a negative-sense, single-stranded rna genome that infect vertebrates, invertebrates or plants. this ecological diversity is reflected by the diversity and complexity of their genomes. five canonical structural protein genes are conserved in all rhabdoviruses, but may be overprinted, overlapped or interspersed with several novel and diverse accessory genes. this review gives an overview of the charact ...	2017	27773769
rabies vaccine development by expression of recombinant viral glycoprotein.	the rabies virus envelope glycoprotein (rvgp) is the main antigen of rabies virus and is the only viral component present in all new rabies vaccines being proposed. many approaches have been taken since dna recombinant technology became available to express an immunogenic recombinant rabies virus glycoprotein (rrvgp). these attempts are reviewed here, and the relevant results are discussed with respect to the general characteristics of the rrvgp, the expression system used, the expression levels ...	2017	27796547
trileucine residues in a ligand-cpp-based sirna delivery platform improve endosomal escape of sirna.	sirna entrapment within endosomes is a significant problem encountered with sirna delivery platforms that co-opt receptor-mediated entry pathways. attachment of a cell-penetrating peptide (cpp), such as nona-arginine (9r) to a cell receptor-binding ligand like the rabies virus glycoprotein, rvg, allows effective sirna delivery to the cytoplasm by non-endocytic pathways, but a significant amount of sirna complexes also enters the cell by ligand-induced receptor endocytosis and remain localized in ...	2017	27820977
rabies in poland in 2013 and 2014	evaluation of the epidemiological situation of rabies in poland in 2013 and 2014 in comparison to the previous years.	2017	27870541
a novel rabies vaccine expressing cxcl13 enhances humoral immunity by recruiting both t follicular helper and germinal center b cells.	rabies remains a public health threat in most parts of the world, and approximately 99% of the cases are transmitted by dogs. there is an urgent need to develop an efficacious and affordable vaccine to control canine-transmitted rabies in developing countries. our previous studies demonstrate that overexpression of chemokines/cytokines such as ccl-3 (mip-1α) and granulocyte-macrophage colony-stimulating factor (gm-csf) can enhance the immunogenicity of rabies vaccines. in the present study, the ...	2017	27852854
mechanism of membrane fusion induced by vesicular stomatitis virus g protein.	the glycoproteins (g proteins) of vesicular stomatitis virus (vsv) and related rhabdoviruses (e.g., rabies virus) mediate both cell attachment and membrane fusion. the reversibility of their fusogenic conformational transitions differentiates them from many other low-ph-induced viral fusion proteins. we report single-virion fusion experiments, using methods developed in previous publications to probe fusion of influenza and west nile viruses. we show that a three-stage model fits vsv single-part ...	2017	27974607
monosynaptic tracing in developing circuits using modified rabies virus.	an attenuated rabies virus that expresses fluorescent protein has made it possible to analyze retrograde (presynaptic) monosynaptic connections in vivo. by combining attenuated rabies virus with a cre-loxp based system to target cells in a subtype-specific fashion, it is possible to examine neuronal input in vivo onto any class of neuron, in development and in the mature brain. we describe here the methods to amplify deletion mutant, pseudotyped rabies virus, selectively target cells of interest ...	2017	27943201
dual anterograde and retrograde viral tracing of reciprocal connectivity.	current large-scale approaches in neuroscience aim to unravel the complete connectivity map of specific neuronal circuits, or even the entire brain. this emerging research discipline has been termed connectomics. recombinant glycoprotein-deleted rabies virus (rabv ∆g) has become an important tool for the investigation of neuronal connectivity in the brains of a variety of species. neuronal infection with even a single rabv ∆g particle results in high-level transgene expression, revealing the fin ...	2017	27943199
targeted delivery of nano-ptx to the brain tumor-associated macrophages.	nanoparticles containing mixed lipid monolayer shell, biodegradable polymer core and rabies virus glycoprotein (rvg) peptide as brain targeting ligand, were developed for brain targeted delivery of paclitaxel (ptx) to treat malignant glioma. rvg conjugated ptx loaded nps (rvg-ptx-nps) had the desirable size (~140 nm), narrow size distribution and spherical shape. rvg-ptx-nps showed poor uptake by neurons and selective targeting to the brain tumor associated macrophages (tams) with controlled rel ...	2017	28036254
parahippocampal and retrosplenial connections of rat posterior parietal cortex.	the posterior parietal cortex has been implicated in spatial functions, including navigation. the hippocampal and parahippocampal region and the retrosplenial cortex are crucially involved in navigational processes and connections between the parahippocampal/retrosplenial domain and the posterior parietal cortex have been described. however, an integrated account of the organization of these connections is lacking. here, we investigated parahippocampal connections of each posterior parietal subd ...	2017	28032674
challenges to eliminate rabies virus infection in china by 2020.		2017	28017558
pseudo-typed semliki forest virus delivers egfp into neurons.	semliki forest virus (sfv), a neurotropic virus, has been used to deliver heterologous genes into cells in vitro and in vivo. in this study, we constructed a reporter sfv4-fl-egfp and found that it can deliver egfp into neurons located at the injection site without disseminating throughout the brain. lacking of the capsid gene of sfv4-fl-egfp does not block its life cycle, while forming replication-competent virus-like particles (vlps). these vlps hold subviral genome by using the packaging sequ ...	2017	27739033
rabies viruses leader rna interacts with host hsc70 and inhibits virus replication.	viruses have been shown to be equipped with regulatory rnas to evade host defense system. it has long been known that rabies virus (rabv) transcribes a small regulatory rna, leader rna (lerna), which mediates the transition from viral rna transcription to replication. however, the detailed molecular mechanism remains enigmatic. in the present study, we determined the genetic architecture of rabv lerna and demonstrated its inhibitory effect on replication of wild-type rabies, drv-ah08. the rna im ...	2017	28388579
successful strategies implemented towards the elimination of canine rabies in the western hemisphere.	almost all cases of human rabies result from dog bites, making the elimination of canine rabies a global priority. during recent decades, many countries in the western hemisphere have carried out large-scale dog vaccination campaigns, controlled their free-ranging dog populations and enforced legislation for responsible pet ownership. this article reviews progress in eliminating canine rabies from the western hemisphere. after briefly summarizing the history of control efforts and describing the ...	2017	28385500
the history of rabies in the western hemisphere.	before the introduction of control programs in the 20th century, rabies in domestic dogs occurred throughout the western hemisphere. however, historical records and phylogenetic analysis of multiple virus isolates indicate that, before the arrival of the first european colonizers, rabies virus was likely present only in bats and skunks. canine rabies was either rare or absent among domestic dogs of native americans, and first arrived when many new dog breeds were imported during the period of eu ...	2017	28365457
status of laboratory biosafety and biosecurity in veterinary research facilities in nigeria.	this study determined current status of laboratory biosafety in nigerian veterinary research facilities.	2017	28344841
a dna logic gate automaton for detection of rabies and other lyssaviruses.	immediate activation of biosensors is not always desirable, particularly if activation is due to non-specific interactions. here we demonstrate the use of deoxyribozyme-based logic gate networks arranged into visual displays to precisely control activation of biosensors, and demonstrate a prototype molecular automaton able to discriminate between seven different genotypes of lyssaviruses, including rabies virus. the device uses novel mixed-base logic gates to enable detection of the large divers ...	2017	28342196
a permanent host shift of rabies virus from chiroptera to carnivora associated with recombination.	bat virus host shifts can result in the spread of diseases with significant effects. the rabies virus (rabv) is able to infect almost all mammals and is therefore a useful model for the study of host shift mechanisms. carnivore rabvs originated from two historical host shifts from bat viruses. to reveal the genetic pathways by which bat rabvs changed their host tropism from bats to carnivores, we investigated the second permanent bat-to-carnivore shift resulting in two carnivore variants, known ...	2017	28325933
ecological niche modeling of rabies in the changing arctic of alaska.	rabies is a disease of global significance including in the circumpolar arctic. in alaska enzootic rabies persist in northern and western coastal areas. only sporadic cases have occurred in areas outside of the regions considered enzootic for the virus, such as the interior of the state and urbanized regions.	2017	28320440
engineering a growth sensor to select intracellular antibodies in the cytosol of mammalian cells.	intracellular antibodies (intrabodies) are expected to function as therapeutics as well as tools for elucidating in vivo function of proteins. in this study, we propose a novel intrabody selection method in the cytosol of mammalian cells by utilizing a growth signal, induced by the interaction of the target antigen and an scfv-c-kit growth sensor. here, we challenge this method to select specific intrabodies against rabies virus nucleoprotein (rv-n) for the first time. as a result, we successful ...	2017	28319021
barriers to innovation in human rabies prophylaxis and treatment: a causal analysis of insights from key opinion leaders and literature.	rabies is an essentially 100% fatal, zoonotic disease, caused by lyssaviruses. currently, the disease is vaccine-preventable with pre- and post-exposure prophylaxis (prep and pep). still, rabies virus is estimated to cause up to 60,000 human deaths annually, of which the vast majority occurs in rural asia and africa, due to the inaccessibility of prophylaxis and non-existence of treatment. despite these unmet clinical needs, rabies control mainly focuses on the sylvatic reservoir and drug innova ...	2017	28318148
safety, tolerability and efficacy of intradermal rabies immunization with debioject™.	in a single-center study, 66 healthy volunteers aged between 18 and 50years were randomized to be immunized against rabies with three different injection routes: intradermal with debioject™ (idj), standard intradermal with classical needle (ids), also called mantoux method, and intramuscular with classical needle (im). "vaccin rabique pasteur®" and saline solution (nacl 0.9%) were administered at d0, d7 and d28. antigen doses for both intradermal routes were 1/5 of the dose for im. tolerability, ...	2017	28317660
correction to: huey, rachel, hawthorne, susan, the potential use of rabies virus glycoprotein-derived peptides to facilitate drug delivery into the central nervous system: a mini review.		2017	28316247
barriers to dog rabies vaccination during an urban rabies outbreak: qualitative findings from arequipa, peru.	canine rabies was reintroduced to the city of arequipa, peru in march 2015. the ministry of health has conducted a series of mass dog vaccination campaigns to contain the outbreak, but canine rabies virus transmission continues in arequipa's complex urban environment, putting the city's 1 million inhabitants at risk of infection. the proximate driver of canine rabies in arequipa is low dog vaccination coverage. our objectives were to qualitatively assess barriers to and facilitators of rabies va ...	2017	28306717
management and modeling approaches for controlling raccoon rabies: the road to elimination.	rabies is an ancient viral disease that significantly impacts human and animal health throughout the world. in the developing parts of the world, dog bites represent the highest risk of rabies infection to people, livestock, and other animals. however, in north america, where several rabies virus variants currently circulate in wildlife, human contact with the raccoon rabies variant leads to the highest per capita population administration of post-exposure prophylaxis (pep) annually. previous ra ...	2017	28301480
lyssaviruses and rabies: current conundrums, concerns, contradictions and controversies.	lyssaviruses are bullet-shaped, single-stranded, negative-sense rna viruses and the causative agents of the ancient zoonosis rabies. africa is the likely home to the ancestors of taxa residing within the genus lyssavirus, family rhabdoviridae. diverse lyssaviruses are envisioned as co-evolving with bats, as the ultimate reservoirs, over seemingly millions of years. in terms of relative distribution, overt abundance, and resulting progeny, rabies virus is the most successful lyssavirus species to ...	2017	28299201
disynaptic subthalamic input to the posterior cerebellum in rat.	in the last decade, the interplay between basal ganglia and cerebellar functions has been increasingly advocated to explain their joint operation in both normal and pathological conditions. yet, insight into the neuroanatomical basis of this interplay between both subcortical structures remains sparse and is mainly derived from work in primates. here, in rodents, we have studied the existence of a potential disynaptic connection between the subthalamic nucleus (stn) and the cerebellar cortex as ...	2017	28293179
large-scale reconstructions and independent, unbiased clustering based on morphological metrics to classify neurons in selective populations.	this protocol outlines large-scale reconstructions of neurons combined with the use of independent and unbiased clustering analyses to create a comprehensive survey of the morphological characteristics observed among a selective neuronal population. combination of these techniques constitutes a novel approach for the collection and analysis of neuroanatomical data. together, these techniques enable large-scale, and therefore more comprehensive, sampling of selective neuronal populations and esta ...	2017	28287546
impact of caspase-1/11, -3, -7, or il-1β/il-18 deficiency on rabies virus-induced macrophage cell death and onset of disease.	rabies virus is a highly neurovirulent rna virus, which causes about 59000 deaths in humans each year. previously, we described macrophage cytotoxicity upon infection with rabies virus. here we examined the type of cell death and the role of specific caspases in cell death and disease development upon infection with two laboratory strains of rabies virus: challenge virus standard strain-11 (cvs-11) is highly neurotropic and lethal for mice, while the attenuated evelyn-rotnycki-abelseth (era) str ...	2017	28280602
enhanced transport of plant-produced rabies single chain antibody-rvg peptide fusion protein across an in cellulo blood-brain barrier device.	the biomedical applications of antibody engineering are developing rapidly and have been expanded to plant expression platforms. in the present study, we have generated a novel antibody molecule in planta for targeted delivery across the blood-brain barrier (bbb). rabies virus (rabv) is a neurotropic virus for which there is no effective treatment after entry into the central nervous system (cns). this study investigated the use of a rabv glycoprotein peptide sequence to assist delivery of a rab ...	2017	28273388
alum adjuvanted rabies dna vaccine confers 80% protection against lethal 50 ld50 rabies challenge virus standard strain.	rabies is a serious concern world-wide. despite availability of rabies vaccines for long; their efficacy, safety, availability and cost effectiveness has been a tremendous issue. this calls for improvement of rabies vaccination strategies. dna vaccination has immense potential in this regard. the dna vaccine pgp.lamp-1 conferred 60% protection to balb/c mice against 20 ld50 rabies challenge virus standard (cvs) strain challenge. upon supplementation with emulsigen-d, the vaccine formulation conf ...	2017	28267643
elimination of dog-mediated human rabies deaths by 2030: needs assessment and alternatives for progress based on dog vaccination.	rabies imposes a substantial burden to about half of the world population. the world health organization (who), world organization for animal health, and the food and agriculture organization have set the goal of eliminating dog-mediated human rabies deaths by 2030. this could be achieved largely by massive administration of post-exposure prophylaxis-in perpetuity-, through elimination of dog rabies, or combining both. here, we focused on the resources needed for the elimination of dog rabies vi ...	2017	28239608
serological evidence of lyssavirus infection among bats in nagaland, a north-eastern state in india.	bats are known to be reservoirs of several medically important viruses including lyssaviruses. however, no systematic surveillance for bat rabies has been carried out in india, a canine rabies endemic country with a high burden of human rabies. surveillance for rabies virus (rabv) infection in bats was therefore carried out in nagaland, a north-eastern state in india at sites with intense human-bat interfaces during traditional bat harvests. brain tissues and sera from bats were tested for evide ...	2017	28228179
the control of eye movements by the cerebellar nuclei: polysynaptic projections from the fastigial, interpositus posterior and dentate nuclei to lateral rectus motoneurons in primates.	premotor circuits driving extraocular motoneurons and downstream motor outputs of cerebellar nuclei are well known. however, there is, as yet, no unequivocal account of cerebellar output pathways controlling eye movements in primates. using retrograde transneuronal transfer of rabies virus from the lateral rectus (lr) eye muscle, we studied polysynaptic pathways to lr motoneurons in primates. injections were placed either into the central or distal muscle portion, to identify innervation differe ...	2017	28226411
the phylodynamics of the rabies virus in the russian federation.	near complete rabies virus n gene sequences (1,110 nt) were determined for 82 isolates obtained from different regions of russia between 2008 and 2016. these sequences were analyzed together with 108 representative genbank sequences from 1977-2016 using the bayesian coalescent approach. the timing of the major evolutionary events was estimated. most of the isolates represented the steppe rabies virus group c, which was found over a vast geographic region from central russia to mongolia and split ...	2017	28225771