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predicted 3d model of the rabies virus glycoprotein trimer.the rabvg ectodomain is a homotrimer, and trimers are often called spikes. they are responsible for the attachment of the virus through the interaction with nicotinic acetylcholine receptors, neural cell adhesion molecule (ncam), and the p75 neurotrophin receptor (p75ntr). this makes them relevant in viral pathogenesis. the antigenic structure differs significantly between the trimers and monomers. surfaces rich in hydrophobic amino acids are important for trimer stabilization in which the c-ter ...201627294109
human rabies - wyoming and utah, 2015.in september 2015, a wyoming woman was admitted to a local hospital with a 5-day history of progressive weakness, ataxia, dysarthria, and dysphagia. because of respiratory failure, she was transferred to a referral hospital in utah, where she developed progressive encephalitis. on day 8 of hospitalization, the patient's family told clinicians they recalled that, 1 month before admission, the woman had found a bat on her neck upon waking, but had not sought medical care. the patient's husband sub ...201627253630
intracellular spread of rabies virus is reduced in the paralytic form of canine rabies compared to the furious form.studies of the furious and paralytic forms of canine rabies at the early stage of disease have shown a more rapid viral colonization of the cerebral hemispheres in the furious form, as measured by viral antigen within neuronal cell bodies and viral rna levels. measurement of cellular processes separate from neuronal cell body provides a visual record of the spread of rabies virus which occurs across synapses. in this study, the amount of rabies viral antigen within cell processes was quantitativ ...201627253394
the co-chaperone cdc37 regulates the rabies virus phosphoprotein stability by targeting to hsp90aa1 machinery.cdc37, as a kinase-specific co-chaperone of the chaperone hsp90aa1 (hsp90), actively aids with the maturation, stabilization and activation of the cellular or viral kinase/kinase-like targets. phosphoprotein (p) of rabies virus (rabv) is a multifunctional, non-kinase protein involved in interferon antagonism, viral transcription and replication. here, we demonstrated that the rabv non-kinase p is chaperoned by cdc37 and hsp90 during infection. we found that cdc37 and hsp90 affect the rabv life c ...201627251758
[creation of dna vaccine vector based on codon-optimized gene of rabies virus glycoprotein (g protein) with consensus amino acid sequence].an optimized design of the rabies virus glycoprotein (g protein) for use within dna vaccines has been suggested. the design represents a territorially adapted antigen constructed taking into account glycoprotein amino acid sequences of the rabies viruses registered in the russian federation and the vaccine vnukovo-32 strain. based on the created consensus amino acid sequence, the nucleotide codon-optimized sequence of this modified glycoprotein was obtained and cloned into the pvax1 plasmid (a v ...201627239860
impact of recombinant drosophila s2 cell population enrichment on expression of rabies virus glycoprotein.recombinant drosophila s2 cells have been used for the expression of many proteins of medical interest. however, membrane-attached glycoproteins, which commonly exhibit lower expression levels compared to soluble proteins, may require special procedures in order to attain high levels of expression. in this study, two s2 cell population enrichment methods (antibiotic and immunomagnetic selection) were evaluated for their ability to enhance expression of the membrane-anchored rabies virus glycopro ...201627216014
the rabies virus l protein catalyzes mrna capping with gdp polyribonucleotidyltransferase activity.the large (l) protein of rabies virus (rabv) plays multiple enzymatic roles in viral rna synthesis and processing. however, none of its putative enzymatic activities have been directly demonstrated in vitro. in this study, we expressed and purified a recombinant form of the rabv l protein and verified its guanosine 5'-triphosphatase and gdp polyribonucleotidyltransferase (prntase) activities, which are essential for viral mrna cap formation by the unconventional mechanism. the rabv l protein cap ...201627213429
overwintering of rabies virus in silver haired bats (lasionycteris noctivagans).silver-haired bats, (lasionycteris noctivagans) are semi-colonial, migratory tree bats that have infrequent contact with humans. despite the species rarity, the l. noctivagans rabies variant is the most commonly reported rabies virus variant (rabv) in domestically acquired human rabies cases in the us. unlike big brown bats (eptesicus fuscus) and little brown bats (myotis lucifugus), l. noctivagans are not considered true hibernators. it is unknown if rabv can overwinter in hibernating l. noctiv ...201627195489
a novel rabies virus lipopeptide provides a better protection by improving the magnitude of dcs activation and t cell responses.besides rabies virus neutralizing antibody, non-neutralizing antibody to internal vital proteins, interferon, and possibly cell-mediated immunity also have a critical role in preventing the infection by rabies virus (rv). we identified novel ctl and th epitopes which could induce lymphocyte proliferation and ifn-γ, il-4 production, and designed linear and branched lipopeptides with these selected ctl and th epitopes. compared to linear construct, branched lipopeptides, especially lipo c, stimula ...201627182006
mxa mediates sumo-induced resistance to vesicular stomatitis virus.multiple cellular pathways are regulated by small ubiquitin-like modifier (sumo) modification, including ubiquitin-mediated proteolysis, signal transduction, innate immunity, and antiviral defense. in the study described in this report, we investigated the effects of sumo on the replication of two members of the rhabdoviridae family, vesicular stomatitis virus (vsv) and rabies virus (rabv). we show that stable expression of sumo in human cells confers resistance to vsv infection in an interferon ...201627170750
shared and distinct retinal input to the mouse superior colliculus and dorsal lateral geniculate nucleus.the mammalian retina conveys the vast majority of information about visual stimuli to two brain regions: the dorsal lateral geniculate nucleus (dlgn) and the superior colliculus (sc). the degree to which retinal ganglion cells (rgcs) send similar or distinct information to the two areas remains unclear despite the important constraints that different patterns of rgc input place on downstream visual processing. to resolve this ambiguity, we injected a glycoprotein-deficient rabies virus coding fo ...201627169509
evaluation of elisa for the detection of rabies virus antibodies from the thoracic liquid and muscle extract samples in the monitoring of fox oral vaccination campaigns.the main goal of oral vaccination of foxes is eradication of rabies in the red fox population as rabies reservoirs. to evaluate the success of vaccination a serological testing is conducted as a part of monitoring program. two different methods are used regarding rabies serology: virus neutralisation test and elisa.201627164987
quantitative proteome profiling of street rabies virus-infected mouse hippocampal synaptosomes.it is well established now that neuronal dysfunction rather than structural damage may be responsible for the development of rabies. in order to explore the underlying mechanisms in rabies virus (rabv) and synaptic dysfunctions, a quantitative proteome profiling was carried out on synaptosome samples from mice hippocampus. synaptosome samples from mice hippocampus were isolated and confirmed by western blot and transmission electron microscopy. synaptosome protein content changes were quantitati ...201627155843
calbindin d28k distribution in neurons and reactive gliosis in cerebellar cortex of natural rabies virus-infected cattle.rabies has been an enigmatic disease because microscopic findings in central nervous system tissues do not always correlate well with the severity of the clinical illness. immunohistochemical staining of the calcium-binding protein calbindin (specifically cbd28k) seems to be the technique most used to identify purkinje neurons under normal and pathological conditions. in the present work, we evaluated cbd28k immunoreactivity in the cerebellar cortex of normal and natural rabies virus (rabv)-infe ...201627154319
development and validation of a quantitative competitive elisa for potency testing of equine anti rabies sera with other potential use.in case of a bite by a rabies infected animal, the world health organisation recommends a prophylactic treatment including the administration of human rabies immunoglobulins (hrigs) or highly purified f(ab')2 fragments produced from equine rabies immunoglobulin (f(ab')2 - erigs). according to international regulation, quality control of f(ab')2 - erigs lots requires potency testing by the in vivo mouse neutralisation test (mnt) prior marketing. however, the strategy of the 3rs (reduce, refine, r ...201627151880
improved monosynaptic neural circuit tracing using engineered rabies virus glycoproteins.monosynaptic rabies virus tracing is a unique and powerful tool used to identify neurons making direct presynaptic connections onto neurons of interest across the entire nervous system. current methods utilize complementation of glycoprotein gene-deleted rabies of the sad b19 strain with its glycoprotein, b19g, to mediate retrograde transsynaptic spread across a single synaptic step. in most conditions, this method labels only a fraction of input neurons and would thus benefit from improved effi ...201627149846
notes from the field: assessment of health facilities for control of canine rabies - gondar city, amhara region, ethiopia, 2015.rabies is an encephalitic disease that is nearly always fatal after onset of illness. worldwide, rabies kills an estimated 59,000 humans each year (95% confidence interval [ci] = 25,000-159,000); the majority of the deaths are caused by the rabies virus variant that circulates in dogs (1,2). canine rabies is endemic in ethiopia, with an estimated 2,771 human deaths annually (ci = 1,116-12,660) (1-3). annual rabies-associated livestock losses are estimated at >$50 million (usd), making rabies imp ...201627149318
characterization of epitopes on the rabies virus glycoprotein by selection and analysis of escape mutants.the glycoprotein (g) is the only surface protein of the lyssavirus particle and the only viral product known to be capable of eliciting the production of neutralizing antibodies. in this study, the isolation of escape mutants resistant to monoclonal antibody (mab) neutralization was attempted by a selection strategy employing four distinct rabies virus strains: the extensively passaged evelyn rokitnicki abelseth (era) strain and three field isolates representing two bat-associated variants and t ...201627132040
bayesian spatiotemporal pattern and eco-climatological drivers of striped skunk rabies in the north central plains.striped skunks are one of the most important terrestrial reservoirs of rabies virus in north america, and yet the prevalence of rabies among this host is only passively monitored and the disease among this host remains largely unmanaged. oral vaccination campaigns have not efficiently targeted striped skunks, while periodic spillovers of striped skunk variant viruses to other animals, including some domestic animals, are routinely recorded. in this study we evaluated the spatial and spatio-tempo ...201627127994
disinfection protocols for necropsy equipment in rabies laboratories: safety of personnel and diagnostic outcome.in the last decades, molecular techniques have gradually been adopted for the rapid confirmation of results obtained through gold standard methods. however, international organisations discourage their use in routine laboratory investigations for rabies post-mortem diagnosis, as they may lead to false positive results due to cross-contamination. cleaning and disinfection are essential to prevent cross-contamination of samples in the laboratory environment. the present study evaluated the efficac ...201627091100
molecular characterization of canine rabies virus, mali, 2006-2013.we genetically characterized 32 canine rabies viruses isolated in mali during 2006-2013 and identified 3 subgroups that belonged to the africa 2 lineage. we also detected subgroup f rabies virus. this information should be useful for development of mass vaccination campaigns for dogs and eventual large-scale control programs in this country.201627089307
development of rabies virus-like particles for vaccine applications: production, characterization, and protection studies.rabies is a viral infection of the central nervous system for which vaccination is the only treatment possible. besides preexposure, vaccination is highly recommended for people living in endemic areas, veterinarians, and laboratory workers. our group has developed rabies virus-like particles (rv-vlps) with immunogenic features expressed in mammalian cells for vaccine applications. in this chapter the methods to obtain and characterize a stable hek293 cell line expressing rv-vlps are detailed. f ...201627076129
immunogenicity of multi-epitope-based vaccine candidates administered with the adjuvant gp96 against rabies.rabies, a zoonotic disease, causes > 55,000 human deaths globally and results in at least 500 million dollars in losses every year. the currently available rabies vaccines are mainly inactivated and attenuated vaccines, which have been linked with clinical diseases in animals. thus, a rabies vaccine with high safety and efficacy is urgently needed. peptide vaccines are known for their low cost, simple production procedures and high safety. therefore, in this study, we examined the efficacy of mu ...201627068655
revealing the micro-scale signature of endemic zoonotic disease transmission in an african urban setting.the development of novel approaches that combine epidemiological and genomic data provides new opportunities to reveal the spatiotemporal dynamics of infectious diseases and determine the processes responsible for their spread and maintenance. taking advantage of detailed epidemiological time series and viral sequence data from more than 20 years reported by the national reference centre for rabies of bangui, the capital city of central african republic, we used a combination of mathematical mod ...201627058957
complete genome sequence of a vampire bat rabies virus from french guiana.a rabies virus was detected in a common vampire bat (desmodus rotundus) in french guiana. its genomic sequence was obtained and found to be closely related to other hematophagous bat-related viruses that widely circulate in the northern amazon region. this virus is named at6.201627056216
brain-wide maps of synaptic input to cortical interneurons.cortical inhibition is mediated by diverse inhibitory neuron types that can each play distinct roles in information processing by virtue of differences in their input sources, intrinsic properties, and innervation targets. previous studies in brain slices have demonstrated considerable cell-type specificity in laminar sources of local inputs. in contrast, little is known about possible differences in distant inputs to different cortical interneuron types. we used the monosynaptic rabies virus sy ...201627053207
virological and serological diagnosis of rabies in bats from an urban area in the brazilian amazon.the outbreaks of rabies in humans transmitted by desmodus rotundus in 2004 and 2005, in the northeast of the brazilian state of para, eastern amazon basin, made this a priority area for studies on this zoonosis. given this, the present study provides data on this phenomenon in an urban context, in order to assess the possible circulation of the classic rabies virus (rabv) among bat species in capanema, a town in the amazon basin. bats were collected, in 2011, with mist nets during the wet and dr ...201527049703
co-culture: a quick approach for isolation of street rabies virus in murine neuroblastoma cells.laboratory detection of rabies in most cases is based on detection of the antigen by fluorescent antibody test, however, in weak positive cases confirmative laboratory diagnosis depends on widely accepted mouse inoculation test. cell lines like neuroblastoma have been used to isolate the virus with greater success not only to target for diagnosis, but also for molecular studies that determine the epidemiology of the circulating street rabies strains and in studies that look at the efficiency of ...201527047148
reverse genetics in high throughput: rapid generation of complete negative strand rna virus cdna clones and recombinant viruses thereof.reverse genetics approaches are indispensable tools for proof of concepts in virus replication and pathogenesis. for negative strand rna viruses (nsvs) the limited number of infectious cdna clones represents a bottleneck as clones are often generated from cell culture adapted or attenuated viruses, with limited potential for pathogenesis research. we developed a system in which cdna copies of complete nsv genomes were directly cloned into reverse genetics vectors by linear-to-linear rede/t recom ...201627046474
survival of a newborn from a pregnant woman with rabies infection.rabies is very common in people's republic of china. each year thousands of people die because of this disease, but rabies diagnosed in pregnancy is very rare.201627042172
the importance of immune evasion in the pathogenesis of rabies virus.rabies is a zoonotic disease caused by the lyssavirus rabies virus (rabv) that can infect most mammals, including humans, where it has a case-fatality rate of almost 100%. although preventable by vaccination, rabies causes c. 59,000 human fatalities every year worldwide. thus, there exists an urgent need to establish an effective therapy and/or improve dissemination of vaccines for humans and animals. these outcomes require greater understanding of the mechanisms of rabv pathogenesis to identify ...201627041139
laboratory diagnostics in dog-mediated rabies: an overview of performance and a proposed strategy for various settings.the diagnosis of dog-mediated rabies in humans and animals has greatly benefited from technical advances in the laboratory setting. approaches to diagnosis now include the detection of rabies virus (rabv), rabv rna, or rabv antigens. these assays are important tools in the current efforts aimed at the global elimination of dog-mediated rabies. the assays available for use in laboratories are reviewed herein, as well as their strengths and weaknesses, which vary with the types of sample analyzed. ...201627005282
a case of fatal serotonin syndrome-like human rabies caused by tricolored bat-associated rabies virus.human rabies is a fatal disease, transmitted by saliva of infected animals, and the diagnosis requires a high index of suspicion. very few cases are reported annually in the united states. we present a case of human rabies without a clear exposure history that masqueraded as serotonin syndrome.201627001756
spatial temporal dynamics and molecular evolution of re-emerging rabies virus in taiwan.taiwan has been recognized by the world organization for animal health as rabies-free since 1961. surprisingly, rabies virus (rabv) was identified in a dead formosan ferret badger in july 2013. later, more infected ferret badgers were reported from different geographic regions of taiwan. in order to know its evolutionary history and spatial temporal dynamics of this virus, phylogeny was reconstructed by maximum likelihood and bayesian methods based on the full-length of glycoprotein (g), matrix ...201626999115
retrospective diagnosis of two rabies cases in humans by high throughput sequencing.rabies is prevalent in 150 countries and is definitely found in russian federation. the average registered incidence of rabies infection among animals in russia is 3000 cases per year. at least 500,000 cases of animal bites and scratches are registered in the russia every year, but only 2-4 cases of rabies infection in humans are reported per year. this relatively low incidence of rabies infection among humans is the result of a well-organized program of rabies surveillance and control as well a ...201626998568
one-year immunogenicity kinetics and safety of a purified chick embryo cell rabies vaccine and an inactivated vero cell-derived japanese encephalitis vaccine administered concomitantly according to a new, 1-week, accelerated primary series.conventional rabies pre-exposure prophylaxis (prep) and japanese encephalitis (je) primary series vaccination regimens each require up to 4 weeks to complete and, thus, may not be feasible for individuals who need these immunizations on short notice. this phase 3b, randomized, controlled, observer-blind study evaluated the immunogenicity and safety of concomitant administration of a purified chick embryo cell culture rabies vaccine and an inactivated, adsorbed je vaccine according to an accelera ...201626994987
development of broad-spectrum human monoclonal antibodies for rabies post-exposure prophylaxis.currently available rabies post-exposure prophylaxis (pep) for use in humans includes equine or human rabies immunoglobulins (rig). the replacement of rig with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing rig. in this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to rig in rabies pep. memory b cells from four selected vaccinated donors wer ...201626992832
human rabies - missouri, 2014.on september 18, 2014, the missouri department of health and senior services (mdhss) was notified of a suspected rabies case in a missouri resident. the patient, a man aged 52 years, lived in a rural, deeply wooded area, and bat sightings in and around his home were anecdotally reported. exposure to bats poses a risk for rabies. after two emergency department visits for severe neck pain, paresthesia in the left arm, upper body tremors, and anxiety, he was hospitalized on september 13 for encepha ...201626985578
rabies in costa rica: documentation of the surveillance program and the endemic situation from 1985 to 2014.this is the first comprehensive epidemiological analysis of rabies in costa rica. we characterized the occurrence of the disease and demonstrated its endemic nature in this country. in costa rica, as in other countries in latin america, hematophagous vampire bats are the primary wildlife vectors transmitting the rabies virus to cattle herds. between 1985 and 2014, a total of 78 outbreaks of bovine rabies was reported in costa rica, with documented cases of 723 dead cattle. of cattle outbreaks, 8 ...201626982168
toxoplasmosis may lead to road kills of persian leopards ( panthera pardus saxicolor) in golestan national park, iran.three persian leopards ( panthera pardus saxicolor) that died from car accidents in golestan national park, iran, were tested for toxoplasma gondii and rabies virus infection. acute t. gondii infection was diagnosed in two persian leopards; no rabies virus was detected. acute toxoplasmosis may be a factor in persian leopard road kills.201626981691
everything you always wanted to know about rabies virus (but were afraid to ask).the cultural impact of rabies, the fatal neurological disease caused by infection with rabies virus, registers throughout recorded history. although rabies has been the subject of large-scale public health interventions, chiefly through vaccination efforts, the disease continues to take the lives of about 40,000-70,000 people per year, roughly 40% of whom are children. most of these deaths occur in resource-poor countries, where lack of infrastructure prevents timely reporting and postexposure p ...201526958924
a recombinant rabies virus carrying gfp between n and p affects viral transcription in vitro.several studies have demonstrated the rabies virus to be a perfect potential vaccine vector to insert foreign genes into the target genome. for this study, a green fluorescent protein (gfp) gene was cloned into the rabies virus (rabv) genome between the n and p gene. ct dinucleotide was inserted as intergenic region. the recombinant high egg passage flury strain (hep-flury) of rabv, carrying gfp (rhep-np-gfp), was generated in bhk-21 cells using reverse genetics. according to the viral growth ki ...201626957093
rabies transmission risks during peripartum--two cases and a review of the literature.we report two cases of probable rabies in near-term/at-term pregnant women in sub-saharan africa and asia. one baby was delivered by caesarean section and the other one vaginally. both received post-exposure prophylaxis (pep), including rig and vaccine and both are alive and healthy, at 9 and 24 months, respectively. we found 14 other published cases of infants born from rabid mothers. one confirmed case of rabies transmission occurred. the other children born from rabid mothers, with or without ...201626947499
synonymous codon usage pattern in glycoprotein gene of rabies virus.rabies virus (rabv) is the causative agent of a fatal nervous system ailment. the disease is zoonotic and prevalent in many developing countries. the glycoprotein (g) of rabv is the major antigenic determinant of the virus and plays a pivotal role in its neurovirulence. various aspects of 'g' protein biology have been explored, but the factors affecting the nucleotide choice and synonymous codon usage have never been reported. in the present study, we have analyzed the relative synonymous codon ...201626945626
nuclear trafficking of the rabies virus interferon antagonist p-protein is regulated by an importin-binding nuclear localization sequence in the c-terminal domain.rabies virus p-protein is expressed as five isoforms (p1-p5) which undergo nucleocytoplasmic trafficking important to roles in immune evasion. although nuclear import of p3 is known to be mediated by an importin (imp)-recognised nuclear localization sequence in the n-terminal region (n-nls), the mechanisms underlying nuclear import of other p isoforms in which the n-nls is inactive or has been deleted have remained unresolved. based on the previous observation that mutation of basic residues k21 ...201626939125
interferon-inducible gtpase: a novel viral response protein involved in rabies virus infection.rabies virus infection is a major public health concern because of its wide host-interference spectrum and nearly 100 % lethality. however, the interactions between host and virus remain unclear. to decipher the authentic response in the central nervous system after rabies virus infection, a dynamic analysis of brain proteome alteration was performed. in this study, 104 significantly differentially expressed proteins were identified, and intermediate filament, interferon-inducible gtpases, and l ...201626906695
rabies post-exposure prophylaxis for a child with severe allergic reaction to rabies vaccine.most adverse events (aes) during the immunization of rabies vaccine were slight, there was little information about the allergic reaction induced by rabies vaccines and had to stop or change the immunization program. here, we reported a case that a 4-year-old boy had category ii exposure to rabies and showed severe allergic reaction after being immunized with lyophilized purified vero cell rabies vaccine (pvrv). after the anti-allergy therapy with hormone, allergy testing indicated medium allerg ...201626900624
molecular genetic characterization of rabies virus glycoprotein gene sequences from rabid dogs in bangkok and neighboring provinces in thailand, 2013-2014.because of its association with dogs, rabies virus (rabv) is still endemic in thailand, where it is a serious public health problem. the genetic characterization of rabv in thailand is limited. therefore, in this study, we investigated the molecular epidemiology and genetic diversity of rabv in the endemic area. viral rna from 48 brain specimens from rabid dogs, collected in bangkok and seven neighboring provinces in 2013-2014, was extracted and sequenced. the complete rabies glycoprotein (g) ge ...201626887972
molecular optimization of rabies virus glycoprotein expression in pichia pastoris.in this work, different approaches were investigated to enhance the expression rabies virus glycoprotein (rabv-g) in the yeast pichia pastoris; this membrane protein is responsible for the synthesis of rabies neutralizing antibodies. first, the impact of synonymous codon usage bias was examined and an optimized rabv-g gene was synthesized. nevertheless, data showed that the secretion of the optimized rabv-g gene was not tremendously increased as compared with the non-optimized one. in addition, ...201626880068
isatis indigotica root polysaccharides as adjuvants for an inactivated rabies virus vaccine.adjuvants can enhance vaccine immunogenicity and induce long-term enhancement of immune responses. thus, adjuvants are important for vaccine research. polysaccharides isolated from select chinese herbs have been demonstrated to possess various beneficial functions and excellent adjuvant abilities. in the present study, the polysaccharides iip-a-1 and iip-2 were isolated from isatis indigotica root and compared with the common vaccine adjuvant aluminum hydroxide via intramuscular co-administratio ...201626875535
generation of recombinant rabies viruses encoding nanoluc luciferase for antiviral activity assays.rabies is an invariably fatal disease caused by rabies virus (rabv), a member of the family rhabdoviridae, genus lyssavirus. once central nervous infection occurs and symptoms develop, the case fatality rate approaches 100% despite availability of post-exposure prophylaxis. therefore, new antiviral therapies for rabies are urgently required. antivirals which can inhibit virus replication can be identified through screening of small compounds, however, as rabv infection does not generate easily d ...201626869397
molecular epidemiological tracing of a cattle rabies outbreak lasting less than a month in rio grande do sul in southern brazil.vampire bat-transmitted cattle rabies cases are typically encountered in areas where the disease is endemic. however, over the period of a month in 2009, an outbreak of cattle rabies occurred and then ended spontaneously in a small area of the rio grande do sul state in southern brazil. to investigate the epidemiological characteristics of this rabies outbreak in rio grande do sul, 26 nucleotide sequences of rabies virus (rabv) genomes that were collected in this area were analyzed phylogenetica ...201626868014
immunogenicity and efficacy of rabivac vaccine for animal rabies control in morocco.to fight animal rabies, moroccan veterinary authorities organize annual dog mass vaccination campaigns using rabivac vaccine, an inactivated adjuvanted cell culture veterinary rabies vaccine. two experiments were undertaken to assess the efficacy and immunogenicity of rabivac.201626866025
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
a three-year (2011-2013) surveillance on animal bites and victims vaccination in the south of khorasan-e-razavi province, iran.rabies is acute encephalitis caused by rabies virus and is transmissible between humans and warm blooded animals. the virus is belong to the family of rabdoviridae and, of lissavirus genus.201526816921
the importance of wild canids in the epidemiology of rabies in northeast brazil: a retrospective study.rabies is an endemic disease in brazil, where it is considered a serious public health problem. although the number of human and dog-transmitted cases has declined in recent decades, rabies in wildlife has emerged considerably. among the sylvatic animals, wild canids have been considered important hosts of the rabies virus. we performed a retrospective study of reported cases of rabies in wild canids and human victims in ceará state (northeast brazil) during 2003 to 2013. information was provide ...201626815766
silencing ccr2 in macrophages alleviates adipose tissue inflammation and the associated metabolic syndrome in dietary obese mice.adipose tissue macrophage (atm)-mediated inflammation is a key feature contributing to the adverse metabolic outcomes of dietary obesity. recruitment of macrophages to obese adipose tissues (at) can occur through the engagement of ccr2, the receptor for mcp-1 (monocyte chemoattractant protein-1), which is expressed on peripheral monocytes/macrophages. here, we show that i.p. administration of a rabies virus glycoprotein-derived acetylcholine receptor-binding peptide effectively delivers complexe ...201626812653
bioecological drivers of rabies virus circulation in a neotropical bat community.in addition to the commonly accepted importance of the vampire bat in the maintenance and transmission of the rabies virus (rabv) in south america, rabv infection of other species is widely evidenced, challenging their role in the viral cycle.201626808820
rabies virus cvs-n2c(δg) strain enhances retrograde synaptic transfer and neuronal viability.virally based transsynaptic tracing technologies are powerful experimental tools for neuronal circuit mapping. the glycoprotein-deletion variant of the sad-b19 vaccine strain rabies virus (rabv) has been the reagent of choice in monosynaptic tracing, since it permits the mapping of synaptic inputs to genetically marked neurons. since its introduction, new helper viruses and reagents that facilitate complementation have enhanced the efficiency of sad-b19(δg) transsynaptic transfer, but there has ...201626804990
a simple alternative to stereotactic injection for brain specific knockdown of mirna.micrornas (mirnas) are key regulators of gene expression. in the brain, vital processes like neurodevelopment and neuronal functions depend on the correct expression of micrornas. perturbation of micrornas in the brain can be used to model neurodegenerative diseases by modulating neuronal cell death. currently, stereotactic injection is used to deliver mirna knockdown agents to specific location in the brain. here, we discuss strategies to design antagomirs against mirna with locked nucleotide m ...201526779762
a novel rabies vaccine based-on toll-like receptor 3 (tlr3) agonist pika adjuvant exhibiting excellent safety and efficacy in animal studies.vaccination alone is not sufficiently effective to protect human from post-exposure rabies virus infection due to delayed generation of rabies virus neutralizing antibodies and weak cellular immunity. therefore, it is vital to develop safer and more efficacious vaccine against rabies. pika, a stabilized chemical analog of double-stranded rna that interacts with tlr3, was employed as adjuvant of rabies vaccine. the efficacy and safety of pika rabies vaccine were evaluated. the results showed that ...201626765968
intravenous administration of brain-targeted stable nucleic acid lipid particles alleviates machado-joseph disease neurological phenotype.others and we showed that rna interference holds great promise for the treatment of dominantly inherited neurodegenerative disorders such as machado-joseph disease (mjd), for which there is no available treatment. however, successful experiments involved intracranial administration of viral vectors and there is a need for a safer and less invasive procedure. in this work, we successfully generated stable nucleic acid lipid particles (snalps), incorporating a short peptide derived from rabies vir ...201626757259
theranostic gas-generating nanoparticles for targeted ultrasound imaging and treatment of neuroblastoma.the development of safe and efficient diagnostic/therapeutic agents for treating cancer in clinics remains challenging due to the potential toxicity of conventional agents. although the annual incidence of neuroblastoma is not that high, the disease mainly occurs in children, a population vulnerable to toxic contrast agents and therapeutics. we demonstrate here that cancer-targeting, gas-generating polymeric nanoparticles are useful as a theranostic tool for ultrasound (us) imaging and treating ...201626739549
[the infectious and pathogenic characteristics of rabies virus strain ctncec25].to investigate the phenotypic characteristics of the strain of the rabies virus ctncec25, the strain of the china rabies virus ctn-1 adapted to primary chicken embryo cells (cecs), vero cells, and mouse neuroblastoma n2a cells was inoculated with ctncec25 and parental ctn-1 strains to explore the cytopathic effect (cpe) and growth kinetics of ctncec25 on cultured cells. to determine the pathogenicity of ctncec25, suckling mice, adult mice, guinea pigs and rabbits were inoculated with ctncec25 vi ...201526738284
inactivation of rabies virus by hydrogen peroxide.development of safe and protective vaccines against infectious pathogens remains a challenge. inactivation of rabies virus is a critical step in the production of vaccines and other research reagents. beta-propiolactone (βpl); the currently used inactivating agent for rabies virus is expensive and proved to be carcinogenic in animals. this study aimed to investigate the ability of hydrogen peroxide (h2o2) to irreversibly inactivate rabies virus without affecting its antigenicity and immunogenici ...201626731189
anterograde or retrograde transsynaptic circuit tracing in vertebrates with vesicular stomatitis virus vectors.viruses have been used as transsynaptic tracers, allowing one to map the inputs and outputs of neuronal populations, due to their ability to replicate in neurons and transmit in vivo only across synaptically connected cells. to date, their use has been largely restricted to mammals. in order to explore the use of such viruses in an expanded host range, we tested the transsynaptic tracing ability of recombinant vesicular stomatitis virus (rvsv) vectors in a variety of organisms. successful infect ...201626729030
early postnatal maturation in vestibulospinal pathways involved in neck and forelimb motor control.to assess the organization and functional development of vestibulospinal inputs to cervical motoneurons (mns), we have used electrophysiology (ventral root and electromyographic [emg] recording), calcium imaging, trans-synaptic rabies virus (rv) and conventional retrograde tracing and immunohistochemistry in the neonatal mouse. by stimulating the viiith nerve electrically while recording synaptically mediated calcium responses in mns, we characterized the inputs from the three vestibulospinal tr ...201626724676
[effect of free-roaming dogs culling on the control of canine rabies].in the peruvian city of arequipa, rabid dogs have been detected since march 2015, signaling the reintroduction of the rabies virus (rv) in this previously officially-declared rabies free zone. high dog density is considered one of the causes for the continuous transmission of the rv in the outbreak in the city of arequipa, which seemingly lends support to the culling of dogs as a public health measure. however, the effectiveness of culling free-roaming dogs to control urban rabies has not been e ...201728327849
profile of cytokines and chemokines triggered by wild-type strains of rabies virus in mice.rabies is a lethal infectious disease that causes 55,000 human deaths per year and is transmitted by various mammalian species, such as dogs and bats. the host immune response is essential for avoiding viral progression and promoting viral clearance. cytokines and chemokines are crucial in the development of an immediate antiviral response; the rabies virus (rabv) attempts to evade this immune response. the virus's capacity for evasion is correlated with its pathogenicity and the host's inflamma ...201626711511
evidence of two distinct phylogenetic lineages of dog rabies virus circulating in cambodia.this first extensive retrospective study of the molecular epidemiology of dog rabies in cambodia included 149 rabies virus (rabv) entire nucleoprotein sequences obtained from 1998-2011. the sequences were analyzed in conjunction with rabvs from other asian countries. phylogenetic reconstruction confirmed the south-east asian phylogenetic clade comprising viruses from cambodia, vietnam, thailand, laos and myanmar. the present study represents the first attempt to classify the phylogenetic lineage ...201626705238
factors associated with dog rabies immunisation status in bamako, mali.we conducted a cross-sectional survey in bamako, mali, to determine for the first time the seroprevalence of rabies virus antibodies in the dog population and people's knowledge, attitudes and practices (kap) towards the disease and its control. antibody detection was done with the fluorescent antibody virus neutralisation (favn) test, with a positivity threshold of 0.25iu/ml. we visited 2956 households in 2010 and 2011 and found 379 dogs in 279 households. data were collected on 279 dog-owning ...201726691990
correlation of inducible nitric oxide synthase (inos) inhibition with tnf-α, caspase-1, fasl and tlr-3 in pathogenesis of rabies in mouse model.the role of inflammatory cytokines such as interleukin-1α/β (il-1α/β), il-6, il-10, tumour necrosis factor-alpha (tnf-α), interferons, nitric oxide (no) and inducible nitric oxide synthase (inos) in pathogenesis of rabies is being actively pursued. presently, levels of certain immune molecules in pathogenesis of rabies in mice have been investigated. cvs strain of rabies infection resulted in early increase in inos, tnf-α, caspase-1, fas ligand (fasl) and toll-like receptor-3 (tlr-3) mrna levels ...201626690069
rabies in a dog imported from egypt with a falsified rabies vaccination certificate--virginia, 2015.canine rabies virus variant has been eliminated in the united states and multiple other countries. globally, however, dogs remain the principal source for human rabies infections. the world health organization recommends that when dogs cross international borders, national importing authorities should require an international veterinary certificate attesting that the animal did not show signs of rabies at the time of shipment, was permanently identified, vaccinated, or revaccinated, and had been ...201526678293
single- versus double-dose rabies vaccination in captive african wild dogs (lycaon pictus).the immune responses of 35 captive african wild dogs (lycaon pictus) to an inactivated rabies virus vaccine were evaluated. seventeen animals received one 1-ml dose of inactivated rabies vaccine administered intramuscularly, while 18 received two 1-ml doses given simultaneously but at different injection sites. sera were collected from all animals prior to vaccination and intermittently from a subset of animals between 3 and 49 mo postvaccination. rabies neutralizing serum antibody titers were m ...201526667524
[molecular genetic characteristics of the virus isolated from patients with human acute encephalomyelitis and multiple sclerosis].the study of the antigenic and molecular genetic structure of human acute encephalomyelitis virus (haev) showed a high similarity of the haev n gene with the homologous gene of the fixed rabies virus strain. the results of the nucleotide sequence analysis indicate that haev belongs to the lyssavirus genotype 1. the n gene sequence is the closest to those of the era-cb20-m and rv-97 strains of the rabies virus. the need for further research into the role of the human acute encephalomyelitis virus ...201526665429
population structure of two rabies hosts relative to the known distribution of rabies virus variants in alaska.for pathogens that infect multiple species, the distinction between reservoir hosts and spillover hosts is often difficult. in alaska, three variants of the arctic rabies virus exist with distinct spatial distributions. we tested the hypothesis that rabies virus variant distribution corresponds to the population structure of the primary rabies hosts in alaska, arctic foxes (vulpes lagopus) and red foxes (vulpes vulpes) to possibly distinguish reservoir and spillover hosts. we used mitochondrial ...201626661691
effect of nicotinic acetylcholine receptor alpha 1 (nachrα1) peptides on rabies virus infection in neuronal cells.rabies virus (rabv) is neurotropic and causes acute progressive encephalitis. herein, we report the interaction of nachrα1-subunit peptides with rabv and the effect of these peptides on rabv infection in cultured neuronal cells. peptide sequences derived from torpedo, bovine, human and rats were synthesized and studied for their interactions with rabv using virus capture elisa and peptide immunofluorescence. the results showed specific binding of the nachrα1-subunit peptides to the rabv. in the ...201626656837
molecular and mathematical modeling analyses of inter-island transmission of rabies into a previously rabies-free island in the philippines.rabies is endemic in the philippines and dog bites are a major cause of rabies cases in humans. the rabies control program has not been successful in eliminating rabies because of low vaccination coverage among dogs. therefore, more effective and feasible strategies for rabies control are urgently required in the country. to control rabies, it is very important to know if inter-island transmission can occur because rabies can become endemic once the virus is introduced in areas that previously h ...201626656835
abortively infected astrocytes appear to represent the main source of interferon beta in the virus-infected brain.interferon beta (ifn-β) is a key component of cellular innate immunity in mammals, and it constitutes the first line of defense during viral infection. studies with cultured cells previously showed that almost all nucleated cells are able to produce ifn-β to various extents, but information about the in vivo sources of ifn-β remains incomplete. by applying immunohistochemistry and employing conditional-reporter mice that express firefly luciferase under the control of the ifn-β promoter in eithe ...201526656686
interspecific contact and competition may affect the strength and direction of disease-diversity relationships for directly transmitted microparasites.the frequency of opportunities for transmission is key to the severity of directly transmitted disease outbreaks in multihost communities. transmission opportunities for generalist microparasites often arise from competitive and trophic interactions. additionally, contact heterogeneities within and between species either hinder or promote transmission. general theory incorporating competition and contact heterogeneities for disease-diversity relationships is underdeveloped. here, we present a fo ...201526655572
rabies virus phosphoprotein interacts with ribosomal protein l9 and affects rabies virus replication.rabies virus is a highly neurotropic virus that can cause fatal infection of the central nervous system in warm-blooded animals. the rabv phosphoprotein (p), an essential cofactor of the virus rna-dependent rna polymerase, is required for virus replication. in this study, the ribosomal protein l9, which has functions in protein translation, is identified as p-interacting cellular factor using phage display analysis. direct binding between the l9 and p was confirmed by protein pull-down and co-im ...201626655239
immunoenhancement with flagellin as an adjuvant to whole-killed rabies vaccine in mice.vaccination is the most effective method for preventing rabies virus (rabv) infection in both humans and animals; however, no satisfactory vaccine has been developed for use worldwide. in the present study, we investigated the immunoadjuvant properties of salmonella typhimurium flagellin (fljb, flic, and fljb'-flic) to improve immune responses against the rabies vaccine (rv) and the protective efficacy of the whole-killed rabies vaccine (wkrv) with or without flagellins in balb/c mice. we also c ...201626650039
contribution of the interaction between the rabies virus p protein and i-kappa b kinase ϵ to the inhibition of type i ifn induction signalling.the p protein of rabies virus (rabv) is known to interfere with the phosphorylation of the host ifn regulatory factor 3 (irf-3) and to consequently inhibit type i ifn induction. previous studies, however, have only tested p proteins from laboratory-adapted fixed virus strains, and to the best of our knowledge there is no report about the effect of p proteins from street rabv strains or other lyssaviruses on the irf-3-mediated type i ifn induction system. in this study, we evaluated the inhibitor ...201626647356
growth signalobody selects functional intrabodies in the mammalian cytoplasm.a versatile strategy to inhibit protein functions in the cytoplasmic environment is eagerly anticipated for drug discovery. in this study, we demonstrate a novel system to directly select functional intrabodies from a library in the mammalian cytoplasm. in this system, a target homo-oligomeric antigen is expressed together with a single-chain fv (scfv) library that is linked to the cytoplasmic domain of a receptor tyrosine kinase (rtk) in the cytoplasm of murine interleukin-3 (il-3)-dependent ce ...201626647155
molecular and immunogenic characterization of bhk-21 cell line adapted cvs-11 strain of rabies virus and future prospect in vaccination strategy.development of a cost effective quality vaccine is a key issue in rabies control programme in developing countries. with this perspective, in the present study, challenge virus standard (cvs)-11 strain of rabies virus was adapted to grow in bhk-21 cells, characterized, compared with other viruses including global vaccine strains and field isolates from indian subcontinent and china at molecular level. this cell adapted virus was evaluated for the production of cost effective veterinary vaccine. ...201526645040
why has canine rabies remained endemic in the kilosa district of tanzania? lessons learnt and the way forward.domestic dogs are the main targets for rabies control as they are the principal reservoir for transmission of the rabies virus to humans and other domestic animals. the purpose of this study was to identify the factors that contribute to the rabies virus infecting the human population in a rural community of eastern tanzania.201526631275
recombinant fluorescent rabies virus vectors for tracing neurons and synaptic connections.recombinant rabies virus (rv) vectors expressing fluorescent proteins allow staining of neurons from many mammalian species and enable the study of neuron morphology. because viral spread occurs only between neurons that have synaptic connections, these vectors also permit transsynaptic tracing. a recently established system for restriction of transsynaptic tracing to a single transsynaptic jump, dubbed monosynaptic tracing, uses glycoprotein gene-defective, pseudotyped rv. this allows infection ...201526631133
pseudotyping of g-gene-deficient rabies virus.g-deleted fluorescent rabies virus (rv) pseudotyped with rv g proteins, sad δg egfp (rv cvs-g), can be used as single-round vectors for efficient retrograde labeling of neurons. for these experiments, as well as for monosynaptic tracing, which involves pseudotyping in situ, the use of the cvs strain g is recommended because of its high tropism for neurons. pseudotype virus stocks generated by transfection of pcaggs-g (or in mg139-on cells) contain the g protein of the vaccine strain sad l16, whi ...201526631128
monoclonal antibodies for characterization of rabies virus isolated from non-hematophagous bats in brazil.in brazil, various isolates of rabies virus (rabv) show antigenic profiles distinct from those established by the reduced panel of eight monoclonal antibodies (mabs) determined by the centers for disease control and prevention (cdc), utilized for the antigenic characterization of rabv in the americas. the objective of this study was to produce mabs from rabv isolates from insectivorous bats with an antigenic profile incompatible with the pre-established one.201526623633
altering entry site preference of lentiviral vectors into neuronal cells by pseudotyping with envelope glycoproteins.a lentiviral vector system provides a powerful strategy for gene therapy trials against a variety of neurological and neurodegenerative disorders. pseudotyping of lentiviral vectors with different envelope glycoproteins not only confers the neurotropism to the vectors, but also alters the preference of sites of vector entry into neuronal cells. one major group of lentiviral vectors is a pseudotype with vesicular stomatitis virus glycoprotein (vsv-g) that enters preferentially cell body areas (so ...201626611586
running rewires the neuronal network of adult-born dentate granule cells.exercise improves cognition in humans and animals. running increases neurogenesis in the dentate gyrus of the hippocampus, a brain area important for learning and memory. it is unclear how running modifies the circuitry of new dentate gyrus neurons to support their role in memory function. here we combine retroviral labeling with rabies virus mediated trans-synaptic retrograde tracing to define and quantify new neuron afferent inputs in young adult male c57bl/6 mice, housed with or without a run ...201626589333
optical imaging and gene therapy with neuroblastoma-targeting polymeric nanoparticles for potential theranostic applications.recently, targeted delivery systems based on functionalized polymeric nanoparticles have attracted a great deal of attention in cancer diagnosis and therapy. specifically, as neuroblastoma occurs in infancy and childhood, targeted delivery may be critical to reduce the side effects that can occur with conventional approaches, as well as to achieve precise diagnosis and efficient therapy. thus, biocompatible poly(d,l-lactide-co-glycolide) (plg) nanoparticles containing an imaging probe and therap ...201626573885
immunostained plaque assay for detection and titration of rabies virus infectivity.the fluorescent antibody test (fat) is the most commonly used method for detection of the rabies virus (rv). the plaque assay can only be applied to fixed rvs, and cannot be used for street rvs. in this study, plaque formation allowing the determination of both fixed and street rvs was achieved using the immune plaque assay. the immune plaque assay carried out using both fixed and street rvs showed the formation of clear and countable plaques after immunostaining with anti-rv p monoclonal antibo ...201626569350
pathology and molecular detection of rabies virus in ferret badgers associated with a rabies outbreak in taiwan.until rabies virus (rabv) infection in taiwan ferret badgers (twfb; melogale moschata subaurantiaca) was diagnosed in mid-june 2013, taiwan had been considered rabies free for >50 yr. although rabies has also been reported in ferret badgers in china, the pathologic changes and distribution of viral antigens of ferret badger-associated rabies have not been described. we performed a comprehensive pathologic study and molecular detection of rabies virus in three necropsied rabid twfbs and evaluated ...201626560756
afferent and efferent connections of c1 cells with spinal cord or hypothalamic projections in mice.the axonal projections and synaptic input of the c1 adrenergic neurons of the rostral ventrolateral medulla (vlm) were examined using transgenic dopamine-beta hydroxylase cre mice and modified rabies virus. cre-dependent viral vectors expressing tva (receptor for envelopea) and rabies glycoprotein were injected into the left vlm. envelopea-pseudotyped rabies-egfp glycoprotein-deficient virus (rabies-egfp) was injected 4-6 weeks later in either thoracic spinal cord (sc) or hypothalamus. tva immun ...201626560463
origins of multisynaptic projections from the basal ganglia to the forelimb region of the ventral premotor cortex in macaque monkeys.the ventral premotor cortex (pmv), occupying the ventral aspect of area 6 in the frontal lobe, has been implicated in action planning and execution based on visual signals. although the pmv has been characterized by cortico-cortical connections with specific subregions of the parietal and prefrontal cortical areas, a topographical input/output organization between the pmv and the basal ganglia (bg) still remains elusive. in the present study, retrograde transneuronal labelling with the rabies vi ...201626547510
government response to the discovery of a rabies virus reservoir species on a previously designated rabies-free island, taiwan, 1999-2014.taiwan had been considered rabies free since 1961. in 2013, taiwan confirmed the detection of rabies virus in wild taiwan ferret-badgers. up to december 2014, there have been 423 rabies-confirmed ferret-badgers and three cases of spillover infection into non-reservoir hosts. genetic analysis indicates that tfbv is distinct from all other known rabies virus variants. to date, ferret-badger rabies is known to occur only in china and taiwan. the temporal dynamics of rabid ferret-badgers in taiwan s ...201626542085
a case report on indirect transmission of human rabies.at present, virus infection is still a common threat to public health in developing countries. human rabies remains a matter of great global concern with a case-fatality of almost 100%. the rabies virus belongs to the neurotropic type of virus of the lyssavirus genus, and the disease presents as a deteriorating encephalomyelitis and is endemic throughout much of the world, particularly in africa and asia. previous data have shown that, globally, approximately 59 000 human deaths are caused by ra ...201526537216
a vl-linker-vh orientation dependent single chain variable antibody fragment against rabies virus g protein with enhanced neutralizing potency in vivo.lethal rabies can be prevented effectively by post-exposure prophylactic (pep) with rabies immunoglobulin (rig). single-chain variable fragment (scfv), which is composed of a variable heavy chain (vh) and variable light chain (vl) connected by a peptide linker, may be developed as alternative to rig for neutralizing rabies virus (rv). however, our previously constructed scfv (fv57s) with the (nh2) vh-linker-vl (cooh) orientation showed a lower neutralizing potency than its parent rig. this orien ...201626497316
rabies epidemiology and control in ecuador.describe the epidemiology and the control effort for rabies in ecuador.201526493436
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