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whole-brain mapping of the inputs and outputs of the medial part of the olfactory tubercle.the medial part of the olfactory tubercle (ot) is a brain structure located at the interface of the reward and olfactory system. it is closely related to pheromone-rewards, natural reinforcement, addiction and many other behaviors. however, the structure of the anatomic circuitry of the medial part of the ot is still unclear. in the present study, the medial part of the ot was found to be highly connected with a wide range of brain areas with the help of the pseudorabies virus tracing tool. in o ...201728804450
a time-resolved fluoroimmunoassay to assay the rabies virus glycoprotein: application for estimation of human rabies vaccine potency.replacement of the in vivo rabies vaccine potency test (nih test) by in vitro methods had been discussed by several researcher including who expert working groups. in this paper, a time-resolved fluoroimmunoassay (trfia) for the assay of rabies virus glycoprotein in rabies vaccine was first established to estimate the rabies vaccine potency by using specific monoclonal antibody that only recognized the native, trimeric and immunogenic form of rabies virus glycoprotein. potency of the rabies viru ...201728779162
a genetically modified rabies vaccine (erags) induces protective immunity in dogs and cattle.the current live attenuated rabies vaccine must be replaced with a safer vaccine based on the erags strain to prevent rabies in south korea. we evaluated the safety and immunogenicity of a new strain in dogs and cattle.201728775977
genetic demography at the leading edge of the distribution of a rabies virus vector.the common vampire bat, desmodus rotundus, ranges from south america into northern mexico in north america. this sanguivorous species of bat feeds primarily on medium to large-sized mammals and is known to rely on livestock as primary prey. each year, there are hotspot areas of d. rotundus-specific rabies virus outbreaks that lead to the deaths of livestock and economic losses. based on incidental captures in our study area, which is an area of high cattle mortality from d. rotundus transmitted ...201728770072
molecular function analysis of rabies virus rna polymerase l protein by using an l gene-deficient virus.while the rna-dependent rna polymerase l protein of rabies virus (rabv), a member of the genus lyssavirus of the family rhabdoviridae, has potential to be a therapeutic target for rabies, the molecular functions of this protein have remained largely unknown. in this study, to obtain a novel experimental tool for molecular function analysis of the rabv l protein, we established by using a reverse genetics approach an l gene-deficient rabv (nishi-δl/nluc), which infects, propagates, and correspond ...201728768857
protective immune response of oral rabies vaccine in stray dogs, corsacs and steppe wolves after a single immunization.in this study the safety and protective immunity of an oral rabies vaccine, based on the live, modified rabies virus strain vrc-rz2, was examined in stray dogs (canis sp.), corsacs (vulpes corsac) and steppe wolves (canis lupus campestris). in the safety group (dogs, n=6; corsacs, n=3; wolves, n=3) which was vaccinated with a 10-times field dose/animal, no animals showed any signs of disease or changes in behavior or appetite during the period of clinical observation, similar to the animals in t ...201728766059
hippocampal tert regulates spatial memory formation through modulation of neural development.the molecular mechanism of memory formation remains a mystery. here, we show that tert, the catalytic subunit of telomerase, gene knockout (tert-/-) causes extremely poor ability in spatial memory formation. knockdown of tert in the dentate gyrus of adult hippocampus impairs spatial memory processes, while overexpression facilitates it. we find that tert plays a critical role in neural development including dendritic development and neuritogenesis of hippocampal newborn neurons. a monosynaptic p ...201728757168
characterization of akabane virus from domestic bamboo rat, southern china.to identify the causative agents in 3 large-scale outbreaks of encephalitis and death among farmed bamboo rats (rhizomys pruinosus). the routine bacterial culture and identification were performed. there were no significant pathogenic bacteria isolated from the brain, heart, liver, spleen, lung, or kidney of diseased bamboo rats. using pcr-based methods, we excluded the following as causative agent: pox virus, herpesvirus, adenovirus, lymphocytic choriomeningitis virus, rabies virus, and sendai ...201728757035
safety and immunogenicity of a mrna rabies vaccine in healthy adults: an open-label, non-randomised, prospective, first-in-human phase 1 clinical trial.vaccines based on mrna coding for antigens have been shown to be safe and immunogenic in preclinical models. we aimed to report results of the first-in-human proof-of-concept clinical trial in healthy adults of a prophylactic mrna-based vaccine encoding rabies virus glycoprotein (cv7201).201728754494
neuropathogenesis by chandipura virus: an acute encephalitis syndrome in india.chandipura virus (chpv) has been contributing to the rising number of premature deaths due to acute encephalitis syndrome for over a decade in india. chpv belongs to the family rhabdoviridae. neuropathogenesis of chpv has been well established but the exact route of entry into the central nervous system (cns) and the triggering factor for neuronal death are still unknown. rabies virus and vesicular stomatitis virus, which are related closely to chpv, enter the cns retrogradely from peripheral or ...201728731002
immunological aspects of rabies: a literature review.rabies is a lethal disease caused by the neurotropic virus rabies virus (rabv), and it remains an important public health problem globally. it is known that the host immune response is important for control of viral infection and promoting viral clearance. in this context, it is well documented that, in addition to rabv neutralizing antibody, interferons and cell-mediated immunity also have an important role in preventing the establishment of disease. on the other hand, rabv suppresses host immu ...201728726129
[c-terminal lysosome targeting domain of cd63 modifies cellular localization of rabies virus glycoprotein].the glycoprotein of rabies virus is the central antigen elicited the immune response to infection; therefore, the majority of developing anti-rabies vaccines are based on this protein. in order to increase the efficacy of dna immunogen encoding rabies virus glycoprotein, the construction of chimeric protein with the cd63 domain has been proposed. the cd63 is a transmembrane protein localized on the cell surface and in lysosomes. the lysosome targeting motif gyevm is located at its c-terminus. we ...201728707662
increased transgene expression level of rabies virus vector for transsynaptic tracing.viral vectors that can infect neurons transsynaptically and can strongly express foreign genes are useful for investigating the organization of neural circuits. we previously developed a propagation-competent rabies virus (rv) vector based on a highly attenuated hep-flury strain (rhep5.0-cvsg), which selectively infects neurons and propagates between synaptically connected neurons in a retrograde direction. its relatively low level of transgene expression, however, makes immunostaining necessary ...201728700657
life-long genetic and functional access to neural circuits using self-inactivating rabies virus.neural networks are emerging as the fundamental computational unit of the brain and it is becoming progressively clearer that network dysfunction is at the core of a number of psychiatric and neurodegenerative disorders. yet, our ability to target specific networks for functional or genetic manipulations remains limited. monosynaptically restricted rabies virus facilitates the anatomical investigation of neural circuits. however, the inherent cytotoxicity of the rabies largely prevents its imple ...201728689641
a single center, open label study of intradermal administration of an inactivated purified chick embryo cell culture rabies virus vaccine in adults.in the usa, rabies vaccines (rvs) are licensed for intramuscular (im) use only, although rvs are licensed for use by the intradermal (id) route in many other countries. recent limitations in supplies of rv in the usa reopened discussions on the more efficient use of available biologics, including utilization of more stringent risk assessments, and potential id rv administration. a clinical trial was designed to compare the immunogenic and adverse effects of a purified chicken embryo cell (pcec) ...201728688782
first complete genomic sequence of a rabies virus from the republic of tajikistan obtained directly from a flinders technology associates card.a brain homogenate derived from a rabid dog in the district of tojikobod, republic of tajikistan, was applied to a flinders technology associates (fta) card. a full-genome sequence of rabies virus (rabv) was generated from the fta card directly without extraction, demonstrating the utility of these cards for readily obtaining genetic data.201728684566
lyssavirus phosphoproteins increase mitochondrial complex i activity and levels of reactive oxygen species.we have previously demonstrated that serine residues at positions 162 and 166 of the rabies virus (rabv) phosphoprotein (p) are critical for oxidative stress induced by cvs in cultured cells. we have now evaluated the p of two street rabv variants and mokola (mok) virus. the p of these viruses, like cvs, induces an increase in complex i activities and reactive oxygen species levels in transfected cells. although the sequence homology of p is only 45% with mok (higher for street viruses) and cvs, ...201728681345
negri bodies are viral factories with properties of liquid organelles.replication of mononegavirales occurs in viral factories which form inclusions in the host-cell cytoplasm. for rabies virus, those inclusions are called negri bodies (nbs). we report that nbs have characteristics similar to those of liquid organelles: they are spherical, they fuse to form larger structures, and they disappear upon hypotonic shock. their liquid phase is confirmed by frap experiments. live-cell imaging indicates that viral nucleocapsids are ejected from nbs and transported along m ...201728680096
rabies virus in bats, state of pará, brazil, 2005-2011.rabies is an acute, progressive zoonotic viral infection that in general produces a fatal outcome. this disease is responsible for deaths in humans and animals worldwide and, because it can affect all mammals, is considered one of the most important viral infections for public health. this study aimed to determine the prevalence of rabies in bats of different species found in municipalities of the state of pará from 2005 to 2011. the rabies virus was detected in 12 (0.39%) bats in a total of 310 ...201728678651
striatal cholinergic interneurons and parkinson's disease.giant, aspiny cholinergic interneurons (chis) have long been known to be key nodes in the striatal circuitry controlling goal-directed actions and habits. in recent years, new experimental approaches, like optogenetics and monosynaptic rabies virus mapping, have expanded our understanding of how chis contribute to the striatal activity underlying action selection and the interplay of dopaminergic and cholinergic signaling. these approaches also have begun to reveal how chi function is distorted ...201728677242
defect of rabies virus phosphoprotein in its interferon-antagonist activity negatively affects viral replication in muscle cells.attenuated derivative rabies virus ni-ce replicates in muscle cells less efficiently than does the parental pathogenic strain nishigahara. to examine the mechanism underlying the less efficient replication of ni-ce, we compared the activities of ni-ce and nishigahara phosphoproteins, viral interferon (ifn) antagonists, to suppress ifn-β promoter activity in muscle cells and we demonstrated a defect of ni-ce phosphoprotein in this ability. treatment with an ifn-β-neutralizing antibody improved th ...201728674326
experimental infection of artibeus intermedius with a vampire bat rabies virus.experimental infection of artibeus intermedius, the great fruit-eating bat, was performed with vampire bat rabies isolates. bats (n=35) were captured in the wild and quarantined prior to experimental infection. no rabies antibodies were detected by rapid fluorescent focus inhibition test (rffit) prior to infection. three doses of rabies virus (rv) and three different routes of infection were used. one out of 35 bats died without showing any clinical signs at day 14 and was positive for rabies. n ...201728673461
multivariate analysis of the immune response to a vaccine as an alternative to the repetition of animal challenge studies for vaccines with demonstrated efficacy.the assessment of vaccine combinations, or the evaluation of the impact of minor modifications of one component in well-established vaccines, requires animal challenges in the absence of previously validated correlates of protection. as an alternative, we propose conducting a multivariate analysis of the specific immune response to the vaccine. this approach is consistent with the principles of the 3rs (refinement, reduction and replacement) and avoids repeating efficacy studies based on infecti ...201728669388
monosynaptic retrograde tracing of neurons expressing the g-protein coupled receptor gpr151 in the mouse brain.gpr151 is a g-protein coupled receptor for which the endogenous ligand remains unknown. in the nervous system of vertebrates, its expression is enriched in specific diencephalic structures, where the highest levels are observed in the habenular area. the habenula has been implicated in a range of different functions including behavioral flexibility, decision making, inhibitory control, and pain processing, which makes it a promising target for treating psychiatric and neurological disease. this ...201728657115
using viral gene sequences to compare and explain the heterogeneous spatial dynamics of virus epidemics.rabies is an important zoonotic disease distributed worldwide. a key question in rabies epidemiology is the identification of factors that impact virus dispersion. here we apply new analytical methods, based on phylogeographic reconstructions of viral lineage movement, to undertake a comparative evolutionary-epidemiological study of the spatial dynamics of rabies virus (rabv) epidemics in different hosts and habitats. we have compiled rabv data sets from skunk, raccoon, bat and domestic dog popu ...201728651357
comparison of the protective efficacy between single and combination of recombinant adenoviruses expressing complete and truncated glycoprotein, and nucleoprotein of the pathogenic street rabies virus in mice.rabies is an important viral zoonosis that causes acute encephalitis and death in mammals. to date, several recombinant vaccines have been developed based on g protein, which is considered to be the main antigen, and these vaccines are used for rabies control in many countries. most recombinant viruses expressing rabv g protein retain the g gene from attenuated rabv. not enough is currently known about the protective effect against rabv of a combination of recombinant adenoviruses expressing the ...201728646885
asn194lys mutation in rvg29 peptide increases gfp transgene delivery by endocytosis to neuroblastoma and astrocyte cells.a cell-penetrating peptide-based delivery system could target specific types of cells for therapeutic genes delivery. to increase the gene delivery efficiency into neuronal phenotype cells, we introduced an asn194lys mutation to rvg29 peptide derived from rabies virus glycoprotein and added a nuclear localization signal to enhance its nuclear import.201728643952
rabies - epidemiology, pathogenesis, public health concerns and advances in diagnosis and control: a comprehensive review.rabies is a zoonotic, fatal and progressive neurological infection caused by rabies virus of the genus lyssavirus and family rhabdoviridae. it affects all warm-blooded animals and the disease is prevalent throughout the world and endemic in many countries except in islands like australia and antarctica. over 60,000 peoples die every year due to rabies, while approximately 15 million people receive rabies post-exposure prophylaxis (pep) annually. bite of rabid animals and saliva of infected host ...201728643547
oral vaccination of wildlife against rabies: differences among host species in vaccine uptake efficiency.oral vaccination using attenuated and recombinant rabies vaccines has been proven a powerful tool to combat rabies in wildlife. however, clear differences have been observed in vaccine titers needed to induce a protective immune response against rabies after oral vaccination in different reservoir species. the mechanisms contributing to the observed resistance against oral rabies vaccination in some species are not completely understood. hence, the immunogenicity of the vaccine virus strain, spb ...201728641888
ifit2 is a restriction factor in rabies virus pathogenicity.understanding the interactions between rabies virus (rabv) and individual host cell proteins is critical for the development of targeted therapies. here we report that interferon-induced protein with tetratricopeptide repeats 2 (ifit2), an interferon-stimulated gene (isg) with possible rna-binding capacity, is an important restriction factor for rabies virus. when ifit2 was depleted, rabv grew more quickly in mouse neuroblastoma cells in vitro this effect was replicated in vivo, where ifit2 knoc ...201728637751
serology and protein electrophoresis for evidence of exposure to 12 mink pathogens in free-ranging american mink (neovison vison) in argentina.basic pathologic characteristics for farmed minks were previously reported worldwide. however, its status in the wild has not been studied in detail.201728635524
rabies virus co-localizes with early (rab5) and late (rab7) endosomal proteins in neuronal and sh-sy5y cells.rabies virus (rabv) is a highly neurotropic virus that follows clathrin-mediated endocytosis and ph-dependent pathway for trafficking and invasion into endothelial cells. early (rab5, eea1) and late (rab7, lamp1) endosomal proteins play critical roles in endosomal sorting, maturity and targeting various molecular cargoes, but their precise functions in the early stage of rabv neuronal infection remain elusive. in this study, the relationship between enigmatic entry of rabv with these endosomal p ...201728634871
comparison of g protein sequences of south african street rabies viruses showing distinct progression of the disease in a mouse model of experimental rabies.rabies is a fatal zoonotic disease and infections generally lead to a fatal encephalomyelitis in both humans and animals. in south africa, domestic (dogs) and the wildlife (yellow mongoose) host species maintain the canid and mongoose rabies variants respectively. in this study, pathogenicity differences of south african canid and mongoose rabies viruses were investigated in a murine model, by assessing the progression of clinical signs and survivorship. comparison of glycoprotein gene sequences ...201728627433
exosome mediated delivery of mir-124 promotes neurogenesis after ischemia.the intrinsic ability of neurogenesis after stroke has been proven weak, which results in insufficient repair of injury in the nerve system. recent studies suggest multiple micrornas (mirnas) are involved in the neuroremodeling process. targeted mirnas delivery for amplification of neurogenesis is promising in promoting the prognosis after ischemia. here, we showed that modified exosomes, with rabies virus glycoprotein (rvg) fused to exosomal protein lysosome-associated membrane glycoprotein 2b ...201728624203
april:taci axis is dispensable for the immune response to rabies vaccination.there is significant need to develop a single-dose rabies vaccine to replace the current multi-dose rabies vaccine regimen and eliminate the requirement for rabies immune globulin in post-exposure settings. to accomplish this goal, rabies virus (rabv)-based vaccines must rapidly activate b cells to secrete antibodies which neutralize pathogenic rabv before it enters the cns. increased understanding of how b cells effectively respond to rabv-based vaccines may improve efforts to simplify post-exp ...201728619678
rational design of rabies vaccine formulation for enhanced stability.vaccines are often lyophilized in order to retain their stability and efficacy for a longer period of time. however, the same lyophilization process may also cause a major degradation of the vaccine, especially during early phases of manufacturing, leading to a loss of potency of the product. many viral diseases, such as rabies, are acute and fatal unless the vaccine is administered prior to exposure or the onset of symptoms in the case of postexposure treatment.201728618756
investigation of rabies virus glycoprotein carboxyl terminus as an in vitro predictive tool of neurovirulence. a 3r approach.in the field of live viral vaccines production, there is an unmet need for in vitro tests complying a 3r approach (refine, replace and reduce the use of animal experimentation) to replace the post-licensing safety tests currently assayed in animals. here, we performed a pilot study evaluating whether virulence of rabies virus, rabv, can be forecast by an in vitro test of neurite outgrowth. the rationale to use neurite outgrowth as a read-out for this test is based on the salient property of the ...201728602914
cloning and expression of fragment of the rabies virus nucleoprotein gene in escherichia coli and evaluation of antigenicity of the expression product.rabies virus nucleoprotein (n protein) encapsidates genomic rna of the virus and forms the viral ribonucleoprotein complex. these n proteins represent highly organized structures which activate proliferation of b cells and production antibodies against the n protein. in addition to the b cell, the rabies virus n protein has been shown to induce potent t helper cell responses resulting in a long-lasting and strong humoral immune response. rabies virus n protein is a molecular target of choice for ...201728588631
nicotinic acetylcholine receptor alpha 1(nachrα1) subunit peptides as potential antiviral agents against rabies virus.rabies virus (rabv) is neurotropic and infects all warm-blooded animals. the binding of the virus with host cell receptor components is critical for infection. the present study reports the interaction of nicotinic acetylcholine receptor alpha 1 (nachrα1) peptides with the rabies virus glycoprotein (rabvg) to design potential anti-rabies agents. the nachrα1peptide sequences from different species (bovine, human and electric fish/torpedo) were synthesized and their secondary structures were chara ...201728587964
cross-border spread, lineage displacement and evolutionary rate estimation of rabies virus in yunnan province, china.rabies is an important but underestimated threat to public health, with most cases reported in asia. since 2000, a new epidemic wave of rabies has emerged in yunnan province, southwestern china, which borders three countries in southeast asia.201728578663
a facile way of modifying layered double hydroxide nanoparticles with targeting ligand-conjugated albumin for enhanced delivery to brain tumour cells.active targeting of nanoparticles (nps) for cancer treatment has attracted increasing interest in the past decades. various ligand modification strategies have been used to enhance the targeting of nps to the tumor site. however, how to reproducibly fabricate diverse targeting nps with narrowly changeable biophysiochemical properties remains as a major challenge. in this study, layered double hydroxide (ldh) nps were modified as a target delivery system. two brain tumor targeting ligands, i.e., ...201728574700
flagellin fljb as an adjuvant to the recombinant adenovirus rabies glycoprotein vaccine increases immune responses against rabies in mice.rabies virus (rabv) causes an acute progressive viral encephalitis. although currently licensed vaccines have an excellent safety and efficacy record, the development of a safer and more cost-effective vaccine is still being sought. an e1-deleted, replication-defective human adenovirus type 5 (had5) vector expressing rabv glycoprotein (had5-g) is thought to be a promising candidate vaccine for immune prophylaxis against rabies. salmonella enterica serovar typhimurium (s. typhimurium) flagellin i ...201728550434
the phylogeography of myotis bat-associated rabies viruses across canada.as rabies in carnivores is increasingly controlled throughout much of the americas, bats are emerging as a significant source of rabies virus infection of humans and domestic animals. knowledge of the bat species that maintain rabies is a crucial first step in reducing this public health problem. in north america, several bat species are known to be rabies virus reservoirs but the role of bats of the myotis genus has been unclear due to the scarcity of laboratory confirmed cases and the challeng ...201728542160
assessment of the immunogenicity of rabies vaccine preserved by vaporization and delivered to the duodenal mucosa of gray foxes (urocyon cinereoargenteus).objective to assess the immunogenicity of thermostable live-attenuated rabies virus (rabv) preserved by vaporization (pbv) and delivered to the duodenal mucosa of a wildlife species targeted for an oral vaccination program. animals 8 gray foxes (urocyon cinereoargenteus). procedures endoscopy was used to place rabv pbv (n = 3 foxes), alginate-encapsulated rabv pbv (3 foxes), or nonpreserved rabv (2 foxes) vaccine into the duodenum of foxes. blood samples were collected weekly to monitor the immu ...201728541146
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
investigating the effect of carbon source on rabies virus glycoprotein production in pichia pastoris by a transcriptomic approach.several factors affect protein expression in pichia pastoris, one among them is the carbon source. in this work, we studied the effect of this factor on the expression level of rabies virus glycoprotein (rabv-g) in two recombinant clones harboring seven copies of the gene of interest. the expression was driven either by the constitutive glyceraldehyde-3-phosphate dehydrogenase (gap) promoter or the inducible alcohol oxidase1 (aox1) promoter. clones were compared in terms of cell physiology and c ...201728523730
sero-prevalence of virus neutralizing antibodies for rabies in different groups of dogs following vaccination.mass vaccination of dogs is considered fundamental for national rabies control programmes in sri lanka, as dog is the main reservoir and transmitter of the disease.201728521804
targeting the central nervous system (cns): a review of rabies virus-targeting strategies.the transport of drugs across the blood-brain barrier is challenging. the use of peptide sequences derived from viruses with a central nervous system (cns) tropism is one elegant option. a prominent example is the rabies virus glycopeptide-29 (rvg-29), which is said to enable a targeted brain delivery. although the entry mechanism of the rabies virus into the cns is very well characterized, it is unknown whether rvg-29-functionalized drug delivery systems (ddss) follow this pathway. rvg-29-funct ...201728514853
rapid reverse genetics systems for rhabdoviruses: from forward to reverse and back again.methods to recover recombinant negative strand rna viruses (rnsvs) from cloned cdnas have been significantly improved in more than two decades of nsv reverse genetics . in particular, for non-segmented negative strand rna viruses (nnsvs ) like rhabdoviruses , time-consuming generation of reverse genetics systems by stitching pcr subfragments of genomic rhabdovirus cdnas using ligase-based conventional cloning approaches limited the number of available recombinant virus cdna clones. as genetic va ...201728508221
susceptibility of neuroblastoma cells to rabies virus may be affected by passage number.maintaining a healthy, continuous immortalized cell line is essential for rabies laboratories that perform virus isolation assays and test for the presence of viral neutralizing antibodies. individuals who routinely work with rabies virus, such as rabies laboratory employees, or those who may have a high potential for exposure to rabies virus, including veterinarians, should be tested for the presence of anti-rabies viral neutralizing antibodies (vna) every 6-24 months, depending on potential ex ...201728506631
resurgence of rabies in hungary during 2013-2014: an attempt to track the origin of identified strains.in 2013-2014, accumulation of rabies episodes raised concerns regarding ongoing elimination programme in hungary. nearly four dozen cases were identified over a 13-month period in the central region of the country far behind the immunization zones. although the outbreak was successfully controlled, the origin of disease remained unknown. in this study, we sequenced the partial n and g genes from 47 hungarian rabies virus (rv) strains isolated from the 2013-2014 outbreak. sequencing and phylogene ...201728497505
indigenous wildlife rabies in taiwan: ferret badgers, a long term terrestrial reservoir.the emerging disease of rabies was confirmed in taiwan ferret badgers (fbs) and reported to the world organization for animal health (oie) on july 17, 2013. the spread of wildlife rabies can be related to neighborhood countries in asia. the phylogenetic analysis was conducted by maximum likelihood (ml) methods and the bayesian coalescent approach based on the glycoprotein (g) and nucleoprotein (n) genes. the phylogeographic and spatial temporal dynamics of viral transmission were determined by u ...201728497055
rabies virus infection induces microtubule depolymerization to facilitate viral rna synthesis by upregulating hdac6.rabies virus (rabv) is the cause of rabies, and is associated with severe neurological symptoms, high mortality rate, and a serious threat to human health. although cellular tubulin has recently been identified to be incorporated into rabv particles, the effects of rabv infection on the microtubule cytoskeleton remain poorly understood. in this study, we show that rabv infection induces microtubule depolymerization as observed by confocal microscopy, which is closely associated with the formatio ...201728491824
evolution and antiviral specificities of interferon-induced mx proteins of bats against ebola, influenza, and other rna viruses.bats serve as a reservoir for various, often zoonotic viruses, including significant human pathogens such as ebola and influenza viruses. however, for unknown reasons, viral infections rarely cause clinical symptoms in bats. a tight control of viral replication by the host innate immune defense might contribute to this phenomenon. transcriptomic studies revealed the presence of the interferon-induced antiviral myxovirus resistance (mx) proteins in bats, but detailed functional aspects have not b ...201728490593
predictors and immunological correlates of sublethal mercury exposure in vampire bats.mercury (hg) is a pervasive heavy metal that often enters the environment from anthropogenic sources such as gold mining and agriculture. chronic exposure to hg can impair immune function, reducing the ability of animals to resist or recover from infections. how hg influences immunity and susceptibility remains unknown for bats, which appear immunologically distinct from other mammals and are reservoir hosts of many pathogens of importance to human and animal health. we here quantify total hg (t ...201728484633
comprehensive monosynaptic rabies virus mapping of host connectivity with neural progenitor grafts after spinal cord injury.neural progenitor cells grafted to sites of spinal cord injury have supported electrophysiological and functional recovery in several studies. mechanisms associated with graft-related improvements in outcome appear dependent on functional synaptic integration of graft and host systems, although the extent and diversity of synaptic integration of grafts with hosts are unknown. using transgenic mouse spinal neural progenitor cell grafts expressing the tva and g-protein components of the modified r ...201728479302
emission transformation in cdse/zns quantum dots conjugated to biomolecules.the variation of photoluminescence (pl) spectra in cdse/zns quantum dots (qds) at the conjugation to antibodies (abs) has been investigated and discussed in this paper. two types of cdse/zns qds with different cdse core sizes (5.4 and 6.4nm) and emissions (605 and 655nm) were studied before and after the conjugation to anti-interleukin-10 (il-10) and anti-pseudo rabies virus (prv) abs. the pl high energy shift and asymmetric shape of pl bands have been detected in bioconjugated qds. note that th ...201728477576
organization of dopamine and serotonin system: anatomical and functional mapping of monosynaptic inputs using rabies virus.dopamine and serotonin play critical roles in flexible behaviors and are related to various psychiatric and motor disorders. this paper reviews the global organization of dopamine and serotonin systems through recent findings using a modified rabies virus. we first introduce methods for comprehensive mapping of monosynaptic inputs. we then describe quantitative comparisons across the data regarding monosynaptic inputs to dopamine neurons versus serotonin neurons. there is surprising similarity b ...201728476484
rabies tracing of birthdated dentate granule cells in rat temporal lobe epilepsy.to understand how monosynaptic inputs onto adult-born dentate granule cells (dgcs) are altered in experimental mesial temporal lobe epilepsy (mtle) and whether their integration differs from early-born dgcs that are mature at the time of epileptogenesis.201728470680
type 1 immune mechanisms driven by the response to infection with attenuated rabies virus result in changes in the immune bias of the tumor microenvironment and necrosis of mouse gl261 brain tumors.immunotherapeutic strategies for malignant glioma have to overcome the immunomodulatory activities of m2 monocytes that appear in the circulation and as tumor-associated macrophages (tams). m2 cell products contribute to the growth-promoting attributes of the tumor microenvironment (tme) and bias immunity toward type 2, away from the type 1 mechanisms with antitumor properties. to drive type 1 immunity in cns tissues, we infected gl261 tumor-bearing mice with attenuated rabies virus (rabv). thes ...201728461570
rescue of a wild-type rabies virus from cloned cdna and assessment of the proliferative capacity of recombinant viruses.reverse genetic systems (rgs) have been widely used for fixed rabies virus (rabv) strains. however, rgs, for wild-type (wt) strains, have been seldom reported despite the value of this approach in defining the biological characteristics of these strains. in this work, we developed a wt rgs using a swine-origin rabv strain (gd-sh-01) for the first time. in order to have a better understanding of the contribution and function of individual gene on viral proliferation for wt rabv isolates, we const ...201728447192
roles of multiple globus pallidus territories of monkeys and humans in motivation, cognition and action: an anatomical, physiological and pathophysiological review.the globus pallidus (gp) communicates with widespread cortical areas that support various functions, including motivation, cognition and action. anatomical tract-tracing studies revealed that the anteroventral gp communicates with the medial prefrontal and orbitofrontal cortices, which are involved in motivational control; the anterodorsal gp communicates with the lateral prefrontal cortex, which is involved in cognitive control; and the posterior gp communicates with the frontal motor cortex, w ...201728442999
pathological lesions in the central nervous system and peripheral tissues of ddy mice with street rabies virus (1088 strain).most studies on rabies virus pathogenesis in animal models have employed fixed rabies viruses, and the results of those employing street rabies viruses have been inconsistent. therefore, to clarify the pathogenesis of street rabies virus (1088 strain) in mice, 106 focus forming units were inoculated into the right hindlimb of ddy mice (6 weeks, female). at 3 days postinoculation (dpi), mild inflammation was observed in the hindlimb muscle. at 5 dpi, ganglion cells in the right lumbosacral spinal ...201728428485
geographical clusters and predictors of rabies in three southeastern states.the rabies virus causes progressive encephalomyelitis that is fatal in nearly 100% of untreated cases. in the united states, wildlife act as the primary reservoir for rabies; prevention, surveillance, and control costs remain high. the purpose of this study is to understand the current distribution of wildlife rabies in three southeastern states, with particular focus on raccoons as the primary eastern reservoir, as well as identify demographic and geographic factors which may affect the risk of ...201728418772
community-based survey during rabies outbreaks in rangjung town, trashigang, eastern bhutan, 2016.rabies is a highly fatal disease transmitted through the bite of a rabid animal. human deaths can be prevented by prompt administering of rabies vaccine and rabies immunoglobulin following the exposure. an assessment of community knowledge, awareness and practices on rabies is important during outbreak to understand their preparedness and target educational messages and response activities by the rapid response team.201728415972
targeted drug delivery system to neural cells utilizes the nicotinic acetylcholine receptor.drug delivery to the brain is still a major challenge in the field of therapeutics, especially for large and hydrophilic compounds. in order to achieve drug delivery of therapeutic concentration in the central nervous system, the problematic blood brain barrier (bbb) must be overcome. this work presents the formulation of a targeted nanoparticle-based drug delivery system using a specific neural cell targeting ligand, rabies virus derived peptide (rdp). characterization studies revealed that rdp ...201728412449
rabies acquired through kidney transplantation in a child: a case report.rabies is usually transmitted to humans through bites of infected animals; however, it can rarely be transmitted through deceased donor organs or tissues when not suspected. here, we report a case of rabies transmission in a child. the child was a 5-year-old girl who was admitted to the pediatric intensive care unit with encephalitis of unexplained cause 3.5 months after she received a kidney transplant from a deceased donor. the laboratory and imaging studies did not reveal any explanation for ...201728411355
rabies virus exposure of brazilian free-ranging wildlife from municipalities without clinical cases in humans or in terrestrial wildlife.rabies is a zoonosis that causes thousands of animal and human deaths worldwide. serological studies provide information concerning rabies virus circulation among animals and humans. we evaluated the circulation of the rabies virus in wildlife in nine municipalities of são paulo state, brazil. we took blood samples from 27 terrestrial animals of nine different mammalian species in locations without cases of rabies in human and wild terrestrial mammals. sera were tested with the use of the rapid ...201728406757
comparison of the immunogenicity and safety of the purified chick embryo cell rabies vaccine manufactured in india and germany: a randomized, single blind, multicentre, phase iv clinical study.this phase iv, single blind study assessed the immunogenicity and safety of india-manufactured purified chick embryo cell rabies vaccine (pcecv), compared with a german-manufactured batch obtained by the same production process. a total of 340 participants enrolled at 2 study sites in india were randomized (1:1:1:1) in 4 groups to receive a 5-dose essen regimen with either 1 of the 3 indian batches (pcecv-i) or the german batch (pcecv-g), administered on days (d) 0, 3, 7, 14 and 30. the lot-to-l ...201728406752
pathobiological investigation of naturally infected canine rabies cases from sri lanka.the recommended screening of rabies in 'suspect' animal cases involves testing fresh brain tissue. the preservation of fresh tissue however can be difficult under field conditions and formalin fixation provides a simple alternative that may allow a confirmatory diagnosis. the occurrence and location of histopathological changes and immunohistochemical (ihc) labelling for rabies in formalin fixed paraffin embedded (ffpe) canine brain is described in samples from 57 rabies suspect cases from sri-l ...201728403882
pathological findings in the red fox (vulpes vulpes), stone marten (martes foina) and raccoon dog (nyctereutes procyonoides), with special emphasis on infectious and zoonotic agents in northern germany.anthropogenic landscape changes contributed to the reduction of availability of habitats to wild animals. hence, the presence of wild terrestrial carnivores in urban and peri-urban sites has increased considerably over the years implying an increased risk of interspecies spillover of infectious diseases and the transmission of zoonoses. the present study provides a detailed characterisation of the health status of the red fox (vulpes vulpes), stone marten (martes foina) and raccoon dog (nyctereu ...201728399176
engineering of a novel zipfv using leucine zipper motif against rabies virus glycoprotein g with improved protection potency in vivo.rabies is an acute zoonotic infectious disease with a high fatality rate but is preventable with vaccination and rabies immunoglobulin (rig). the single-chain fv fragment (scfv), a small engineered antigen-binding protein derived from antibody variable heavy (vh) and light (vl) chains connected by a peptide linker, can potentially be used to replace rig. here, we produced two peptides vh-jun-his and vl-fos-ha separately in escherichia coli and assembled them to form zipfv successfully in vitro. ...201728389318
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 ...201728388579
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 ...201728385500
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 ...201728365457
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.201728344841
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 ...201728342196
[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 ...201728327849
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 ...201728325933
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.201728320440
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 ...201728319021
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 ...201728318148
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, ...201728317660
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. 201728316247
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 ...201728306717
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 ...201728301480
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 ...201728299201
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 ...201728293179
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 ...201728287546
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 ...201728280602
the final (oral ebola) vaccine trial on captive chimpanzees?could new oral vaccine technologies protect endangered wildlife against a rising tide of infectious disease? we used captive chimpanzees to test oral delivery of a rabies virus (rabv) vectored vaccine against ebola virus (ebov), a major threat to wild chimpanzees and gorillas. ebov gp and rabv gp-specific antibody titers increased exponentially during the trial, with rates of increase for six orally vaccinated chimpanzees very similar to four intramuscularly vaccinated controls. chimpanzee sera ...201728277549
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 ...201728273388
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 ...201728267643
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 ...201728239608
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 ...201728228179
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 ...201728226411
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 ...201728225771
short interfering rnas targeting a vampire-bat related rabies virus phosphoprotein mrna.the aim of this study was to assess the in vitro and in vivo effects of short-interfering rnas (sirnas) against rabies virus phosphoprotein (p) mrna in a post-infection treatment for rabies as an extension of a previous report (braz j microbiol. 2013 nov 15;44(3):879-82). to this end, rabies virus strain rabv-4005 (related to the desmodus rotundus vampire bat) were used to inoculate bhk-21 cells and mice, and the transfection with each of the sirnas was made with lipofectamine-2000™. in vitro re ...201728223028
application of high-throughput sequencing to whole rabies viral genome characterisation and its use for phylogenetic re-evaluation of a raccoon strain incursion into the province of ontario.raccoon rabies remains a serious public health problem throughout much of the eastern seaboard of north america due to the urban nature of the reservoir host and the many challenges inherent in multi-jurisdictional efforts to administer co-ordinated and comprehensive wildlife rabies control programmes. better understanding of the mechanisms of spread of rabies virus can play a significant role in guiding such control efforts. to facilitate a detailed molecular epidemiological study of raccoon ra ...201728219746
expression of rabies virus glycoprotein in the methylotrophic yeast pichia pastoris.rabies is a fatal disease that can be prevented by vaccination. different approaches were investigated to develop novel human rabies vaccines with improved features compared to the current available vaccines, among them is the use of heterologous gene expression technology. here, we describe the expression of the surface rabies virus glycoprotein (rabv-g), which is the major antigen responsible for the induction of protective immunity, in pichia pastoris. six transformants were selected accordin ...201728218973
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