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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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
differentiated human sh-sy5y cells provide a reductionist model of herpes simplex virus 1 neurotropism.neuron-virus interactions that occur during herpes simplex virus (hsv) infection are not fully understood. neurons are the site of lifelong latency and are a crucial target for long-term suppressive therapy or viral clearance. a reproducible neuronal model of human origin would facilitate studies of hsv and other neurotropic viruses. current neuronal models in the herpesvirus field vary widely and have caveats, including incomplete differentiation, nonhuman origins, or the use of dividing cells ...201728956768
enhanced immune response to rabies viruses by the use of a liposome adjuvant in vaccines.essen regimen, the thai red cross two-site id regimen, zagreb schedule, and the eight-site id regimen are the standard rabies vaccines recommended by the world health organization (who). in this study, a liposomal rabies vaccine (liporv) was developed, which was found to facilitate the production of rabies virus neutralizing antibody (rvna) in balb/c mice. liposome solution was prepared with hydrogenated soya phosphatide and cholesterol. liporv composed of liposome solution and inactivated rabie ...201728953450
identification of two classes of somatosensory neurons that display resistance to retrograde infection by rabies virus.glycoprotein-deleted rabies virus-mediated monosynaptic tracing has become a standard method for neuronal circuit mapping, and is applied to virtually all parts of the rodent nervous system, including the spinal cord and primary sensory neurons. here we identified two classes of unmyelinated sensory neurons (nonpeptidergic and c-fiber low-threshold mechanoreceptor neurons) resistant to direct and trans-synaptic infection from the spinal cord with rabies viruses that carry glycoproteins in their ...201728951448
inhibition of mek-erk1/2-map kinase signalling pathway reduces rabies virus induced pathologies in mouse model.the extracellular signal-regulated kinase (erk) pathway has been shown to regulate pathogenesis of many viral infections, but its role during rabies virus (rv) infection in vivo is not clear. in the present study, we investigated the potential role of mek-erk1/2 signalling pathway in the pathogenesis of rabies in mouse model and its regulatory effects on pro-inflammatory cytokines and other mediators of immunity, and kinetics of immune cells. mice were infected with 25 ld50 of challenge virus st ...201728939254
oral vaccination of wildlife using a vaccinia-rabies-glycoprotein recombinant virus vaccine (raboral v-rg®): a global review.raboral v-rg® is an oral rabies vaccine bait that contains an attenuated ("modified-live") recombinant vaccinia virus vector vaccine expressing the rabies virus glycoprotein gene (v-rg). approximately 250 million doses have been distributed globally since 1987 without any reports of adverse reactions in wildlife or domestic animals since the first licensed recombinant oral rabies vaccine (orv) was released into the environment to immunize wildlife populations against rabies. v-rg is genetically ...201728938920
development of molecular confirmation tools for swift and easy rabies diagnostics.as rabies still represents a major public threat with tens of thousands of deaths per year, particularly in developing countries, adequate surveillance based on rapid and reliable rabies diagnosis for both humans and animals is essential. rabies diagnosis relies on highly sensitive and specific laboratory tests for detection of viral antigens. among those tests, at present the immunofluorescence antibody test is the "gold standard test" for rabies diagnosis, followed by virus isolation in either ...201728938887
single visit rabies pre-exposure priming induces a robust anamnestic antibody response after simulated post-exposure vaccination: results of a dose-finding study.the current standard 3-dose intramuscular rabies prep schedule suffers from a number of disadvantages that severely limit accessibility and availability. the cost of is often prohibitive, it requires 3 visits to the clinic, and there are regular vaccine shortages.201728931127
phosphoprotein gene contributes to the enhanced apoptosis induced by wild-type rabies virus gd-sh-01 in vitro.previous research demonstrated that the matrix protein (m) and glycoprotein (g) of attenuated rabies virus (rabv) strains are involved in the induction of host cell apoptosis. in this work, we show that wild-type (wt) rabv gd-sh-01 induces significantly greater apoptosis than the attenuated strain hep-flury. in order to identify the gene(s) accounting for this phenotype, five recombinant rabvs (rrabvs) were constructed by replacing each single gene of hep-flury with the corresponding gene of gd- ...201728928726
terrestrial animal-derived rabies virus in a juvenile indian flying fox in sri lanka. 201729093322
regulation of nf-κb by the p105-abin2-tpl2 complex and relap43 during rabies virus infection.at the crossroad between the nf-κb and the mapk pathways, the ternary complex composed of p105, abin2 and tpl2 is essential for the host cell response to pathogens. the matrix protein (m) of field isolates of rabies virus was previously shown to disturb the signaling induced by relap43, a nf-κb protein close to rela/p65. here, we investigated how the m protein disturbs the nf-κb pathway in a relap43-dependant manner and the potential involvement of the ternary complex in this mechanism. using a ...201729084252
molecular characterization and phylogenetic relatedness of dog-derived rabies viruses circulating in cameroon between 2010 and 2016.rabies is enzootic among dog populations in some parts of cameroon and the risk of human rabies is thought to be steadily high in these regions. however, the molecular epidemiology of circulating rabies virus (rabv) has been hardly considered in cameroon as well as in most neighboring central african countries. to address this fundamental gap, 76 nucleoprotein (n) gene sequences of dog-derived rabv were obtained from 100 brain specimens sampled in cameroon from 2010 to 2016. studied sequences we ...201729084223
neuronal lrp4 regulates synapse formation in the developing cns.the low-density lipoprotein receptor-related protein 4 (lrp4) is essential in muscle fibers for the establishment of the neuromuscular junction. here, we show that lrp4 is also expressed by embryonic cortical and hippocampal neurons, and that downregulation of lrp4 in these neurons causes a reduction in density of synapses and number of primary dendrites. accordingly, overexpression of lrp4 in cultured neurons had the opposite effect inducing more but shorter primary dendrites with an increased ...201729061639
inhibition of rabies virus replication by interferon-stimulated gene 15 and its activating enzyme uba7.it was reported that isg15 and its activating enzyme uba7 have antiviral functions. however, there is no study to demonstrate whether isg15 and uba7 have anti-rabies virus function. in the current study, in vivo and in vitro anti-rabies virus function of isg15 and uba7 were investigated using rnai technology. the results showed that shrna knock-down of expression of isg15 and uba7 increased the titers of rabv in neuroblastoma cell line na and microglial cell line bv-2 cells and shrna knockdown o ...201729056542
evaluation of immune responses in dogs to oral rabies vaccine under field conditions.during the 20th century parenteral vaccination of dogs at central-point locations was the foundation of successful canine rabies elimination programs in numerous countries. however, countries that remain enzootic for canine rabies have lower infrastructural development compared to countries that have achieved elimination, which may make traditional vaccination methods less successful. alternative vaccination methods for dogs must be considered, such as oral rabies vaccine (orv). in 2016, a tradi ...201729054727
development and characterization of novel chimeric monoclonal antibodies for broad spectrum neutralization of rabies virus.current post-exposure prophylaxis for rabies virus infection has several limitations in terms of supply, cost, safety, and efficacy. attempts to replace human or equine rabies immune globulins (hrig or erig) have been made by several companies and institutes. we developed potent monoclonal antibodies to neutralize a broad spectrum of rabies viruses by screening hybridomas received from the u.s. centers for disease control and prevention (cdc). two kinds of chimeric human antibodies (chimeric #7 ...201729045436
efficacy of the oral rabies virus vaccine strain spbn gasgas in foxes and raccoon dogs.to test the immunogenicity and efficacy of a new oral rabies virus vaccine strain spbn gasgas in wildlife target species, one group of foxes and two groups of raccoon dogs were offered a bait containing 1.7 ml of the vaccine (106.6 ffu/ml; 106.8 ffu/dose) and subsequently challenged approximately 180 days later with a fox rabies virus isolate. one group of raccoon dogs (n=30) received the same challenge dose (100.7 micld50/ml) as the red foxes (n=29). the other group with raccoon dogs (n=28) tog ...201729042202
census and vaccination coverage of owned dog populations in four resource-limited rural communities, mpumalanga province, south africa.dogs (canis familiaris) are often free-roaming in sub-saharan african countries. rabies virus circulates in many of these populations and presents a public health issue. mass vaccination of dog populations is the recommended method to decrease the number of dog and human rabies cases. we describe and compare four populations of dogs and their vaccination coverage in four different villages (hluvukani, athol, utah and dixie) in bushbuckridge municipality, mpumalanga province, south africa. cross- ...201729041786
near-infrared fluorescent protein irfp720 is optimal for in vivo fluorescence imaging of rabies virus infection.in vivo imaging is a noninvasive method that enables real-time monitoring of viral infection dynamics in a small animal, which allows a better understanding of viral pathogenesis. in vivo bioluminescence imaging of virus infection is widely used but, despite its advantage over bioluminescence that no substrate administration is required, fluorescence imaging is not used because of severe autofluorescence. recently, several far-red and near-infrared (nir) fluorescent proteins (fps) have been deve ...201729039733
rabies virus modifies host behaviour through a snake-toxin like region of its glycoprotein that inhibits neurotransmitter receptors in the cns.rabies virus induces drastic behaviour modifications in infected hosts. the mechanisms used to achieve these changes in the host are not known. the main finding of this study is that a region in the rabies virus glycoprotein, with homologies to snake toxins, has the ability to alter behaviour in animals through inhibition of nicotinic acetylcholine receptors present in the central nervous system. this finding provides a novel aspect to virus receptor interaction and host manipulation by pathogen ...201728993633
safety, efficacy and immunogenicity evaluation of the sag2 oral rabies vaccine in formosan ferret badgers.since 2013, rabies cases have been reported among formosan ferret badgers in taiwan, and they have been shown to be the major reservoirs for taiwanese enzootics. to control and eradicate rabies, the authorities plan to implement a vaccination programme. before distributing live vaccines in the field, this study assessed the safety, efficacy, and immunogenicity of sag2 vaccine on ferret badgers by direct oral instillation. after application of 109 tcid50/dose, no virus was excreted into the oral ...201728977009
recombinant newcastle disease virus rl-rvg enhances the apoptosis and inhibits the migration of a549 lung adenocarcinoma cells via regulating alpha 7 nicotinic acetylcholine receptors in vitro.the aim of this study were to investigate the possible pro-apoptotic mechanisms of the recombinant newcastle disease virus (ndv) strain rl-rvg, which expresses the rabies virus glycoprotein, in a549 lung adenocarcinoma cells via the regulation of alpha 7 nicotinic acetylcholine receptors (α7 nachrs) and to analyze the relationships between α7 nachr expression in lung cancer and the clinical pathological features.201728974241
direct conversion of human fibroblasts to functional excitatory cortical neurons integrating into human neural networks.human fibroblasts can be directly converted to several subtypes of neurons, but cortical projection neurons have not been generated.201728962665
a translational study on looming-evoked defensive response and the underlying subcortical pathway in autism.rapidly approaching objects indicating threats can induce defensive response through activating a subcortical pathway comprising superior colliculus (sc), lateral posterior nucleus (lp), and basolateral amygdala (bla). abnormal defensive response has been reported in autism, and impaired synaptic connections could be the underlying mechanism. whether the sc-lp-bla pathway processes looming stimuli abnormally in autism is not clear. here, we found that looming-evoked defensive response is impaire ...201729116187
beyond rabies: are free-ranging skunks (mephitis mephitis) in british columbia reservoirs of emerging infection?wild animal reservoirs are an important source of emerging and zoonotic infection. skunks (mephitis mephitis) are a reservoir of skunk strain rabies virus in canada, with the exception of some areas including the province of british columbia (bc). beyond rabies, the reservoir status of skunks for emerging and zoonotic pathogens in bc is unknown. from march 2011 to february 2015, 50 free-ranging skunks were necropsied and tested for 4 pathogens: influenza a, aleutian disease virus (adv), leptospi ...201726392297
health survey of free-ranging raccoons (procyon lotor) in central park, new york, new york, usa: implications for human and domestic animal health.we conducted health assessments on 113 free-ranging raccoons ( procyon lotor ) in central park, new york city, us, in february 2010, september 2010, and november 2011 in conjunction with a trap-vaccinate-release program to control a raccoon rabies epizootic. five individuals were sampled at two time points for 118 raccoon examinations in total. we tested 13 of 13 and 8 of 13 euthanized raccoons for rabies and canine distemper virus (cdv), respectively, by antigen testing on brain tissue; all wer ...201728135131
inactivated recombinant rabies viruses displaying canine distemper virus glycoproteins induce protective immunity against both pathogens.the development of multivalent vaccines is an attractive methodology for the simultaneous prevention of several infectious diseases in vulnerable populations. both canine distemper virus (cdv) and rabies virus (rabv) cause lethal disease in wild and domestic carnivores. while rabv vaccines are inactivated, the live-attenuated cdv vaccines retain residual virulence for highly susceptible wildlife species. in this study, we developed recombinant bivalent vaccine candidates based on recombinant vac ...201728148801
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
one-health: a safe, efficient, dual-use vaccine for humans and animals against middle east respiratory syndrome coronavirus and rabies virus.middle east respiratory syndrome coronavirus (mers-cov) emerged in 2012 and is a highly pathogenic respiratory virus. there are no treatment options against mers-cov for humans or animals, and there are no large-scale clinical trials for therapies against mers-cov. to address this need, we developed an inactivated rabies virus (rabv) that contains the mers-cov spike (s) protein expressed on its surface. our initial recombinant vaccine, bnsp333-s, expresses a full-length wild-type mers-cov s prot ...201727807241
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
an in vitro rna synthesis assay for rabies virus defines ribonucleoprotein interactions critical for polymerase activity.we report an in vitro rna synthesis assay for the rna-dependent rna polymerase (rdrp) of rabies virus (rabv). we expressed rabv large polymerase protein (l) in insect cells from a recombinant baculovirus vector and the phosphoprotein cofactor (p) in escherichia coli and purified the resulting proteins by affinity and size exclusion chromatography. using chemically synthesized short rna corresponding to the first 19 nucleotides (nt) of the rabies virus genome, we demonstrate that l alone initiate ...201727795419
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
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
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
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