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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
development of in vitro and in vivo rabies virus neutralization assays based on a high-titer pseudovirus system.pseudoviruses are useful virological tools because of their safety and versatility; however the low titer of these viruses substantially limits their wider applications. we developed a highly efficient pseudovirus production system capable of yielding 100 times more rabies pseudovirus than the traditional method. employing the high-titer pseudoviruses, we have developed robust in vitro and in vivo neutralization assays for the evaluation of rabies vaccine, which traditionally relies on live-viru ...201728218278
phenotypic consequences in vivo and in vitro of rearranging the p gene of rabv hep-flury.phosphoprotein (p) of the rabies virus (rabv) is critically required for viral replication and pathogenicity. here we manipulated infectious cdna clones of the rabv hep-flury to translocate the p gene from its wild-type position 2 to 1, 3, or 4 in gene order, using an approach which left the viral nucleotide sequence unaltered. the recovered viruses were evaluated for the levels of gene expression, growth kinetics in cell culture, lethality in suckling mice and protection of mice. the results sh ...201728217116
g-protein based elisa as a potency test for rabies vaccines.the nih test is currently used to assess the potency of rabies vaccine, a key criterion for vaccine release. this test is based on mice immunization followed by intracerebral viral challenge. as part of global efforts to reduce animal experimentation and in the framework of the development of sanofi pasteur next generation, highly-purified vaccine, produced without any material of human or animal origin, we developed an elisa as an alternative to the nih test. this elisa is based on monoclonal a ...201728214171
an effective and simplified do-stat control strategy for production of rabies glycoprotein in pichia pastoris.the glycoprotein (g-protein) of rabies virus is responsible for viral attachment to the host cell surface and induces virus neutralization antibodies. in the present study, the g-protein gene of rabies virus cvs strain was cloned, sequenced and expressed in the yeast, pichia pastoris, as a secreted protein, using a simplified do-stat control feeding strategy. this strategy involves the addition of methanol when the dissolved oxygen (do) level rises above the setpoint avoiding methanol accumulati ...201728189633
modeling the transmission dynamics and control of rabies in china.human rabies was first recorded in ancient china in about 556 bc and is still one of the major public-health problems in china. from 1950 to 2015, 130,494 human rabies cases were reported in mainland china with an average of 1977 cases per year. it is estimated that 95% of these human rabies cases are due to dog bites. the purpose of this article is to provide a review about the models, results, and simulations that we have obtained recently on studying the transmission of rabies in china. we fi ...201728188732
role of systemic injection of rabies immunoglobulin in rabies vaccination.to determine the role of systemic injection of rabies immunoglobulin (rig) in rabies vaccination, we analyzed the level of antibody against rabies virus in the serum of mice that received various doses of rig combined with rabies vaccine. our results indicate that systemic injection of rig does not contribute detectably to passive or adaptive immunization, suggesting that the main function of rig in individuals with category iii exposure is to neutralize rabies virus via immediate local infiltra ...201728188373
autophagy is highly targeted among host comparative proteomes during infection with different virulent rabv strains.rabies virus (rabv) is a neurotropic virus that causes serious disease in humans and animals worldwide. it has been reported that different rabv strains can result in divergent prognoses in animal model. to identify host factors that affect different infection processes, a kinetic analysis of host proteome alterations in mouse brains infected with different virulent rabv strains was performed using isobaric tags for a relative and absolute quantification (itraq)-liquid chromatography-tandem mass ...201728186992
inactivation of rabies virus.rabies virus is a notifiable pathogen that must be handled in high containment facilities where national and international guidelines apply. for the effective inactivation of rabies virus, a number of reagents were tested. virkon s (1%) solution caused more than 4log reduction of rabies virus in culture medium supplemented with 10% foetal calf serum within 1min. isopropyl alcohol (70%) treatment resulted in >3log reduction of rabies virus within 20s when applied at a ratio of 19:1, making it a s ...201728174074
development and validation of sensitive real-time rt-pcr assay for broad detection of rabies virus.rabies virus (rabv) remains one of the most important global zoonotic pathogens. rabv causes rabies, an acute encephalomyelitis associated with a high rate of mortality in humans and animals and affecting different parts of the world, particularly in asia and africa. confirmation of rabies diagnosis relies on laboratory diagnosis, in which molecular techniques such as detection of viral rna by reverse transcription polymerase chain reaction (rt-pcr) are increasingly being used. in this study, tw ...201728174073
the ectodomain of rabies virus glycoprotein determines dendritic cell activation.the immune evasion of wild-type (wt) rabies virus (rabv) has been attributed to its glycoprotein (g), particularly to their inefficiency to bind/enter into dendritic cells (dcs). however, the domain responsible for g-mediated dc activation is not clear. in the present study, attempts were made to map the domain(s) on the g involved in differential dc activation using laboratory-adapted and wt viruses. recombinant rabvs with exchange in each of the structural domains such as signal peptide (sp), ...201728161580
targeting vaccine-induced extrafollicular pathway of b cell differentiation improves rabies postexposure prophylaxis.vaccine-induced b cells differentiate along two pathways. the follicular pathway gives rise to germinal centers (gcs) that can take weeks to fully develop. the extrafollicular pathway gives rise to short-lived plasma cells (pcs) that can rapidly secrete protective antibodies within days of vaccination. rabies virus (rabv) postexposure prophylaxis (pep) requires rapid vaccine-induced humoral immunity for protection. therefore, we hypothesized that targeting extrafollicular b cell responses for ac ...201728148792
rabies virus-inspired silica-coated gold nanorods as a photothermal therapeutic platform for treating brain tumors.rabies virus-inspired silica-coated gold nanorods are fabricated by mimicking size, shape, surface glycoprotein property and in vivo behavior of the rabies virus. these nanorods not only resemble the appearance of the actual rabies virus but also travel into the brain through the neuronal pathway bypassing the blood-brain barrier, and moreover respond to near-infrared laser (808 nm) irradiation, emit heat, and effectively suppress brain tumors.201728134459
becn1-dependent casp2 incomplete autophagy induction by binding to rabies virus phosphoprotein.autophagy is an essential component of host immunity and used by viruses for survival. however, the autophagy signaling pathways involved in virus replication are poorly documented. here, we observed that rabies virus (rabv) infection triggered intracellular autophagosome accumulation and results in incomplete autophagy by inhibiting autophagy flux. subsequently, we found that rabv infection induced the reduction of casp2/caspase 2 and the activation of amp-activated protein kinase (ampk)-akt-mt ...201728129024
nose-to-brain delivery of bace1 sirna loaded in solid lipid nanoparticles for alzheimer's therapy.we designed a delivery system to obtain an efficient and optimal nose-to-brain transport of bace1 sirna, potentially useful in the treatment of alzheimer's disease. we selected a cell-penetrating peptide, the short peptide derived from rabies virus glycoprotein known as rvg-9r, to increase the transcellular pathway in neuronal cells. the optimal molar ratio between rvg-9r and bace1 sirna was elucidated. the complex between the two was then encapsulated. we propose chitosan-coated and uncoated so ...201728126681
immunogenicity, safety and antibody persistence of a purified vero cell cultured rabies vaccine (speeda) administered by the zagreb regimen or essen regimen in post-exposure subjects.to compare the safety, immunogenicity and long-term effect of a purified vero cell cultured rabies vaccine in post-exposure subjects following 2 intramuscular regimens, zagreb or essen regimen.201728121231
an accelerated rabies vaccine schedule based on toll-like receptor 3 (tlr3) agonist pika adjuvant augments rabies virus specific antibody and t cell response in healthy adult volunteers.rabies is a fatal disease where post-exposure prophylaxis (pep) is crucial in preventing infection. however, deaths even after appropriate pep, have been reported. the pika rabies vaccine adjuvant is a tlr3 agonist that activates b and t cells leading to a robust immune response.201728118938
synaptic inputs from stroke-injured brain to grafted human stem cell-derived neurons activated by sensory stimuli.transplanted neurons derived from stem cells have been proposed to improve function in animal models of human disease by various mechanisms such as neuronal replacement. however, whether the grafted neurons receive functional synaptic inputs from the recipient's brain and integrate into host neural circuitry is unknown. here we studied the synaptic inputs from the host brain to grafted cortical neurons derived from human induced pluripotent stem cells after transplantation into stroke-injured ra ...201728115364
re-emerging of rabies in shaanxi province, china, 2009 to 2015.to explore the epidemiological, phylogeographic and migration characteristics of human rabies in shaanxi province, china from 2009 to 2015.201728112421
antigenic and genotypic characterization of rabies virus isolated from bats (mammalia: chiroptera) from municipalities in são paulo state, southeastern brazil.bats have aroused growing attention in the public health sphere because they are considered the main reservoir of rabies virus (rabv) in the americas, in places where canine rabies is under control. antigenic and genetic studies of rabv isolates have been used to describe the epidemiological profile of rabies and to identify possible hosts/reservoirs for different epidemiological cycles. this study describes the antigenic and genotypic characterization of 19 rabv isolates from central nervous sy ...201728108804
whole-brain 3d mapping of human neural transplant innervation.while transplantation represents a key tool for assessing in vivo functionality of neural stem cells and their suitability for neural repair, little is known about the integration of grafted neurons into the host brain circuitry. rabies virus-based retrograde tracing has developed into a powerful approach for visualizing synaptically connected neurons. here, we combine this technique with light sheet fluorescence microscopy (lsfm) to visualize transplanted cells and connected host neurons in who ...201728102196
overexpression of interleukin-7 extends the humoral immune response induced by rabies vaccination.rabies continues to present a public health threat in most countries of the world. the most efficient way to prevent and control rabies is to implement vaccination programs for domestic animals. however, traditional inactivated vaccines used in animals are costly and have relatively low efficiency, which impedes their extensive use in developing countries. there is, therefore, an urgent need to develop single-dose and long-lasting rabies vaccines. however, little information is available regardi ...201728100620
ecological potential for rabies virus transmission via scavenging of dead bats by mesocarnivores.multiple species of bats are reservoirs of rabies virus in the americas and are occasionally the source of spillover infections into mesocarnivore species. although rabies transmission generally is assumed to occur via bite, laboratory studies have demonstrated the potential for rabies transmission via ingestion of rabid animals. we investigated the ecological potential for this mode of transmission by assessing mesocarnivore scavenging behavior of dead bats in suburban habitats of flagstaff, ar ...201728094609
rabies virus vaccine as an immune adjuvant against cancers and glioblastoma: new studies may resurrect a neglected potential.to review the literature about the use of rabies virus-vaccine (rv-v) as an anticancer immunotherapeutic modality in the light of recent findings. the literature search in relevant databases with the following key words: rabies virus, cancer, remission. remissions occured following rv-v injections in patients with cervical cancer and melanoma. pilot clinical studies showed that rv-v injections enhanced survival in glioblastoma patients, which is supported by findings in gl261 mouse glioma model. ...201728093702
expression of interleukin-6 by a recombinant rabies virus enhances its immunogenicity as a potential vaccine.several studies have confirmed that interleukin-6 (il6) mediates multiple biological effects that enhance immune responses when used as an adjuvant. in the present study, recombinant rabies virus (rabv) expressing canine il6 (rhep-cail6) was rescued and its pathogenicity and immunogenicity were investigated in mice. we demonstrated that mice received a single intramuscular immunization with rhep-cail6 showed an earlier increase and higher maximum titres of virus-neutralizing antibody (vna) as we ...201728089546
a pan-lyssavirus taqman real-time rt-pcr assay for the detection of highly variable rabies virus and other lyssaviruses.rabies, resulting from infection by rabies virus (rabv) and related lyssaviruses, is one of the most deadly zoonotic diseases and is responsible for up to 70,000 estimated human deaths worldwide each year. rapid and accurate laboratory diagnosis of rabies is essential for timely administration of post-exposure prophylaxis in humans and control of the disease in animals. currently, only the direct fluorescent antibody (dfa) test is recommended for routine rabies diagnosis. reverse-transcription p ...201728081126
v1 connections reveal a series of elongated higher visual areas in the california ground squirrel, otospermophilus beecheyi.for studies of visual cortex organization, mouse is becoming an increasingly more often used model. in addition to its genetic tractability, the relatively small area of cortical surface devoted to visual processing simplifies efforts in relating the structure of visual cortex to visual function. however, the nature of this compact organization can make some comparisons to the much larger non-human primate visual cortex difficult. the squirrel, as a highly visual rodent offers a useful means for ...201728078786
local circuits of v1 layer 4b neurons projecting to v2 thick stripes define distinct cell classes and avoid cytochrome oxidase blobs.decades of anatomical studies on the primate primary visual cortex (v1) have led to a detailed diagram of v1 intrinsic circuitry, but this diagram lacks information about the output targets of v1 cells. understanding how v1 local processing relates to downstream processing requires identification of neuronal populations defined by their output targets. in primates, v1 layers (l)2/3 and 4b send segregated projections to distinct cytochrome oxidase (co) stripes in area v2: neurons in co blob colum ...201728077720
fusion peptide improves stability and bioactivity of single chain antibody against rabies virus.the combination of rabies immunoglobulin (rig) with a vaccine is currently effective against rabies infections, but improvements are needed. genetic engineering antibody technology is an attractive approach for developing novel antibodies to replace rig. in our previous study, a single-chain variable fragment, scfv57r, against rabies virus glycoprotein (rvgp) was constructed. however, its inherent weak stability and short half-life compared with the parent rig may limit its diagnostic and therap ...201728068664
5'-phospho-rna acceptor specificity of gdp polyribonucleotidyltransferase of vesicular stomatitis virus in mrna capping.the gdp polyribonucleotidyltransferase (prntase) domain of the multifunctional l protein of rhabdoviruses, such as vesicular stomatitis virus (vsv) and rabies virus, catalyzes the transfer of 5'-phospho-rna (prna) from 5'-triphospho-rna (ppprna) to gdp via a covalent enzyme-prna intermediate to generate a 5'-cap structure (gpppa). here, using an improved oligo-rna capping assay with the vsv l protein, we showed that the michaelis constants for gdp and pppaacag (vsv mrna-start sequence) are 0.03 ...201728053102
reduction of animal suffering in rabies vaccine potency testing by introduction of humane endpoints.potency controls of inactivated rabies vaccines for human use are confirmed by the national institutes of health challenge test in which lethal infection with severe neurological symptoms should be observed in approximately half of the mice inoculated with the rabies virus. weight loss, decreased body temperature, and the presence of rabies-associated neurological signs have been proposed as humane endpoints. the potential for reduction of animal suffering by introducing humane endpoints in the ...201728040390
free-roaming dogs in nepal: demographics, health and public knowledge, attitudes and practices.in nepal, most dogs are free to roam and may transmit diseases to humans and animals. these dogs often suffer from malnutrition and lack basic health care. minimal information is available about their demographics and about public attitudes concerning dogs and diseases. we carried out a study in chitwan district (central nepal), to collect baseline data on free-roaming owned dog demographics, assess knowledge, attitudes and practices of dog owners concerning dogs and rabies, evaluate rabies vacc ...201727334892
the potential use of rabies virus glycoprotein-derived peptides to facilitate drug delivery into the central nervous system: a mini review.rabies virus glycoprotein (rvg), a 505 amino acid type-1 glycoprotein, is responsible for the neurotrophic nature of the rabies virus infection. despite varying reports in the literature as to which receptor is ultimately responsible for interaction of rvg with the nervous system, there is a strong argument for major nicotinic acetylcholine receptor (nachr) involvement. peptide derivatives of rvg, such as rabies virus-derived peptide (rdp) and rvg-29 are emerging as promising targeting ligands f ...201727581650
molecular characterization of nucleoprotein gene of rabies virus from maharashtra, india.rabies poses a serious public health concern in developing countries such as india.201726821566
comparison of immune responses to attenuated rabies virus and street virus in mouse brain.rabies is a lethal neurological disease caused by the neurotropic rabies virus (rabv). to investigate the innate immune response in the brain during rabies infection, key gene transcripts indicative of innate immunity in a mouse model system were measured using real-time rt-pcr. mice were infected via the intracerebral or intramuscular route with either attenuated rabies virus (srv9) or pathogenic rabies virus (bd06). infection with srv9 resulted in the early detection of viral replication and t ...201727722994
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
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
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
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
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
rabies screen reveals gpe control of cocaine-triggered plasticity.identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. cocaine increased rabies-labelled inputs from the ...201728902833
a novel approach to a rabies vaccine based on a recombinant single-cycle flavivirus vector.the replivax® vaccine (rv) platform is based on flavivirus genomes that are rationally attenuated by deletion. these single-cycle rv vaccine candidates targeting flavivirus pathogens have been demonstrated to be safe, highly immunogenic, and efficacious in animal models, including non-human primates. here we show utility of the technology for delivery of a non-flavivirus immunogen by engineering several west nile-based rv vectors to express full-length rabies virus g protein. the rabies virus g ...201728899628
immunogenicity of orfv-based vectors expressing the rabies virus glycoprotein in livestock species.the parapoxvirus orf virus (orfv) encodes several immunomodulatory proteins (imps) that modulate host-innate and pro-inflammatory responses and has been proposed as a vaccine delivery vector for use in animal species. here we describe the construction and characterization of two recombinant orfv vectors expressing the rabies virus (rabv) glycoprotein (g). the rabv-g gene was inserted in the orfv024 or orfv121 gene loci, which encode for imps that are unique to parapoxviruses and inhibit activati ...201728898730
a self-killing rabies virus that leaves a trace on the dna.although modified rabies viruses have emerged as a powerful tool for tracing the inputs to genetically defined populations of neurons, the toxicity of the virus has limited its utility. a recent study employed a self-inactivating rabies (sir) virus that enables recording or manipulation of targeted neurons for months.201728890212
generation of a novel live rabies vaccine strain with a high level of safety by introducing attenuating mutations in the nucleoprotein and glycoprotein.the current live rabies vaccine sag2 is attenuated by only one mutation (arg-to-glu) at position 333 in the glycoprotein (g333). this fact generates a potential risk of the emergence of a pathogenic revertant by a back mutation at this position during viral propagation in the body. to circumvent this risk, it is desirable to generate a live vaccine strain highly and stably attenuated by multiple mutations. however, the information on attenuating mutations other than that at g333 is very limited. ...201728882441
vaccines against botulism.botulinum neurotoxins (bont) cause the flaccid paralysis of botulism by inhibiting the release of acetylcholine from motor neurons. there are seven serotypes of bont (a-g), with limited therapies, and no fda approved vaccine for botulism. an investigational formalin-inactivated penta-serotype-bont/a-e toxoid vaccine was used to vaccinate people who are at high risk of contracting botulism. however, this formalin-inactivated penta-serotype-bont/a-e toxoid vaccine was losing potency and was discon ...201728869493
a data platform to improve rabies prevention, sri lanka.in sri lanka, rabies prevention initiatives are hindered by fragmented and delayed information-sharing that limits clinicians' ability to follow patients and impedes public health surveillance.201728867845
recombinant rabies virus expressing il-15 enhances immunogenicity through promoting the activation of dendritic cells in mice.rabies remains a public health threat that kills approximately 59,000 people worldwide each year, most of which are from the developing countries of africa and asia where dog rabies are endemic. therefore, developing an affordable and efficacious vaccine is crucial for rabies control in these countries. interleukin (il)-15, an immunoregulatory cytokine, is a pluripotent molecule with therapeutic potential, which targets many cell types and links the innate and adaptive immune system. in this stu ...201728861771
glycoprotein-g-gene-based molecular and phylogenetic analysis of rabies viruses associated with a large outbreak of bovine rabies in southern brazil.a large outbreak of hematophagous-bat-associated bovine rabies has been occurring in rio grande do sul (rs), the southernmost brazilian state, since 2011, with official estimates exceeding 50,000 cattle deaths. the present article describes a genetic characterization of rabies virus (rabv) recovered from 59 affected cattle and two sheep, from 56 herds in 16 municipalities (2012-2016). molecular analysis was performed using the nucleotide (nt) and predicted amino acid (aa) sequences of rabv glyco ...201728856449
incidence of human rabies and characterization of rabies virus nucleoprotein gene in dogs in fujian province, southeast china, 2002-2012.rabies is a global fatal infectious viral disease that is characterized by a high mortality after onset of clinical symptoms. recently, there has been an increase in the incidence of rabies in china. the aim of this study was to investigate the incidence of human rabies and characterize the rabies virus nucleoprotein gene in dogs sampled from fujian province, southeast china from 2002 to 2012.201728854892
plant-made vaccines and reagents for the one health initiative.the one health initiative is increasingly becoming a prominent discussion topic in animal and human health, with its focus on prevention of spread of zoonotic diseases, both in animals, and from animals to humans. an important part of one health is that diagnostics and vaccines for diseases may be the same thing - and be used for both humans and animals. one potential problem standing in the way of wider adoption of one health principles, though, is that use of conventional cell fermentation sys ...201728846485
comparison of a micro-neutralization test with the rapid fluorescent focus inhibition test for measuring rabies virus neutralizing antibodies.the rapid fluorescent focus inhibition test (rffit) is routinely used in the united states to measure rabies virus neutralizing antibodies (rvna). rffit has a long history of reproducible and reliable results. the test has been modified over the years to use smaller volumes of reagents and samples, but requires a 50 μl minimum volume of test serum. to conduct pathogenesis studies, small laboratory animals such as mice are regularly tested for rvna, but the minimum volume for a standard rffit may ...201728845465
rabies virus transmission in solid organ transplantation, china, 2015-2016.we report rabies virus transmission among solid organ transplantation recipients in changsha, china, in 2016. two recipients were confirmed to have rabies and died. our findings suggest that more attention should be paid to the possibility of rabies virus transmission through organ transplantation for clinical and public health reasons.201728820377
molecular characterization of atypical antigenic variants of canine rabies virus reveals its reintroduction by wildlife vectors in southeastern mexico.rabies is an infectious viral disease that is practically always fatal following the onset of clinical signs. in mexico, the last case of human rabies transmitted by dogs was reported in 2006 and canine rabies has declined significantly due to vaccination campaigns implemented in the country. here we report on the molecular characterization of six rabies virus strains found in yucatan and chiapas, remarkably, four of them showed an atypical reaction pattern when antigenic characterization with a ...201728819692
codon usage bias in the n gene of rabies virus.since its emergence, rabies virus (rabv) has been a major worldwide concern especially in developing countries. the nucleoprotein (n) of rabv is highly conserved and key for genetic typing, thus a better understanding of the n gene evolutionary trajectory can assist the development of control measures. we found that the n gene of rabv has a low codon usage bias with a mean effective number of codons (enc) value of 56.33 influenced by both mutation pressure and natural selection. however, neutral ...201728818621
enhancing immune responses to cancer vaccines using multi-site injections.for a vaccine to be effective it must induce a sufficiently robust and specific immune response. multi-site injection protocols can increase the titers of rabies virus-neutralizing antibodies. hypothetically, spreading a vaccine dose across multiple lymphatic drainage regions could also potentiate t cell responses. we used a replication-deficient adenovirus serotype 5-vectored cancer vaccine targeting the melanoma-associated antigen dopachrome tautomerase. clinically, high numbers of tumor-infil ...201728814733
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
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
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