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cross-border transport of rescue dogs may spread rabies in europe.harmonisation of regulations in the european union and the european economic area, as of january 1, 2012, has led to an increase in the number of rescue dogs imported to norway from eastern european countries, in particular romania. today the only requirements for dogs entering norway are rabies vaccination and prophylactic echinococcus multilocularis treatment. the aim of this study was to investigate the antibody levels to rabies virus in vaccinated rescue dogs and to examine if the dogs had s ...201526113337
host-rabies virus protein-protein interactions as druggable antiviral targets.we present an unconventional approach to antiviral drug discovery, which is used to identify potent small molecules against rabies virus. first, we conceptualized viral capsid assembly as occurring via a host-catalyzed biochemical pathway, in contrast to the classical view of capsid formation by self-assembly. this suggested opportunities for antiviral intervention by targeting previously unappreciated catalytic host proteins, which were pursued. second, we hypothesized these host proteins to be ...201323404707
assessment the efficiency of the constructed minigenome of rabies virus using pv strain as helper virus.rabies is an acute viral disease that causes encephalomyelitis in mammals and human. the only way to prevent this disease is through vaccination before or after exposure. the aim of this study is to evaluate the efficiency of the pasteur virus (pv) minigenome, using pv strain.201627179165
characterization of dendritic morphology and neurotransmitter phenotype of thoracic descending propriospinal neurons after complete spinal cord transection and gdnf treatment.after spinal cord injury (sci), poor regeneration of damaged axons of the central nervous system (cns) causes limited functional recovery. this limited spontaneous functional recovery has been attributed, to a large extent, to the plasticity of propriospinal neurons, especially the descending propriospinal neurons (dpsns). compared with the supraspinal counterparts, dpsns have displayed significantly greater regenerative capacity, which can be further enhanced by glial cell line-derived neurotro ...201626730519
oral immunization of mice with recombinant rabies vaccine strain (erag3g) induces complete protection.new rabies vaccine bait for both pets and raccoon dogs residing in korea is needed to eradicate rabies infection among animals. in this study, we constructed a recombinant rabies virus (rabv), the erag3g strain, using a reverse genetics system. then we investigated the efficacy of this strain in mice after oral administration and the safety of this strain in cats after intramuscular administration.201525648184
a single immunization with recombinant rabies virus (erag3g) confers complete protection against rabies in mice.new alternative bait rabies vaccines applicable to pet dogs and wild animals are needed to eradicate rabies in korea. in this study, recombinant rabies virus, erag3g strain was constructed using reverse genetic system and the safety, efficacy and immunogenicity of the erag3g strain was evaluated in mice and dogs.201425003091
health evaluation and survey of zoonotic pathogens in free-ranging capybaras (hydrochoerus hydrochaeris).capybaras (hydrochoerus hydrochaeris) are the world's largest rodents and play an epidemiologic role in the transmission of zoonotic pathogens, including the causative agents of brazilian spotted fever, leptospirosis, and others. we surveyed the health of 31 free-ranging capybaras at the alberto löfgren state park, são paulo, brazil using a variety of diagnostic methods. hematology and serum chemistry were consistent with mild malnutrition and parasitism but did not indicate severe physiologic i ...201424779462
innate antiviral signalling in the central nervous system.the innate immune system mediates protection against neurotropic viruses capable of infecting the central nervous system (cns). neurotropic viruses include herpes simplex virus (hsv), west nile virus (wnv), rabies virus, la crosse virus, and poliovirus. viral infection triggers activation of pattern recognition receptors (prrs) such as toll-like receptors (tlrs), retinoic acid-inducible gene 1 (rig-i) like receptors (rlrs), nucleotide-binding oligomerization domain (nod)-like receptors (nlrs), a ...201424316012
vascular mineralization in the brain of horses.vascular mineralization (siderocalcinosis) in the brain of horses has been usually assumed to be an incidental age-related finding with no clinic significance. in the present study, eight 15-32-year-old horses of different breeds with cerebral siderocalcinosis were studied. four of these horses had acute and severe central nervous system clinical signs of unknown etiology, 2 horses had neurological signs of known cause, and 2 horses did not have neurological signs. gross examination of the brain ...201222529137
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
purification and on-column refolding of a single-chain antibody fragment against rabies virus glycoprotein expressed in escherichia coli.an anti-rabies virus single-chain antibody fragment of an anti-glycoprotein with the vl-linker-vh orientation, designated scfv57rn, was successfully and conveniently prepared in this study. the scfv57rn protein was mainly expressed in inclusion bodies in escherichia coli. after washing and purification, the inclusion bodies were finally obtained with an on-column refolding procedure. further purification by gel exclusion chromatography was performed to remove inactive multimers. about 360 mg of ...201627157441
commentary: incorporation of membrane-anchored flagellin or escherichia coli heat-labile enterotoxin b subunit enhances the immunogenicity of rabies virus-like particles in mice and dogs. 201526483770
a novel variable antibody fragment dimerized by leucine zippers with enhanced neutralizing potency against rabies virus g protein compared to its corresponding single-chain variable antibody fragment.fatal rabies can be prevented effectively by post-exposure prophylactic (pep) with rabies immunoglobulin (rig). single-chain variable fragments (scfv), which are composed of a variable heavy chain (vh) and a variable light chain (vl) connected by a peptide linker, can potentially be used to replace rig. however, in our previous study, a scfv (scfv57s) specific for the rabies virus (rv) g protein showed a lower neutralizing potency than that of its parent igg due to lower stability and altered pe ...201526325475
incorporation of membrane-anchored flagellin or escherichia coli heat-labile enterotoxin b subunit enhances the immunogenicity of rabies virus-like particles in mice and dogs.rabies remains an important worldwide public health threat, so safe, effective, and affordable vaccines are still being sought. virus-like particle-based vaccines targeting various viral pathogens have been successfully produced, licensed, and commercialized. here, we designed and constructed two chimeric rabies virus-like particles (crvlps) containing rabies virus (rabv) glycoprotein (g), matrix (m) protein, and membrane-anchored flagellin (evlp-f) or escherichia coli heat-labile enterotoxin b ...201525784906
production and characterization of a fusion peptide derived from the rabies virus glycoprotein (rvg29).gene therapy targeting the brain holds great promise in curing nervous system degenerative diseases in clinical applications. with this in mind, in a previous study a 29 amino-acid peptide derived from the rabies virus glycoprotein (rvg29) with a nonamer stretch of arginine residues (rvg29-9r) at its carboxy-terminus was exploited as a ligand for brain-targeting gene delivery. importantly, the report demonstrated that the rvg29-9r vector was able to cross the blood-brain barrier. rvg29-9r is cur ...201425218147
a novel disulfide-stabilized single-chain variable antibody fragment against rabies virus g protein with enhanced in vivo neutralizing potency.rabies is a fatal infectious disease requiring efficient protection provided by post-exposure prophylaxis (pep) with rabies immunoglobulin (rig). the single-chain fv fragment (scfv) is a small engineered antigen binding protein derived from antibody variable heavy (v(h)) and light (v(l)) chains. this novel antibody format may potentially replace the current application of rig to detect and neutralize rabies virus (rv). however, the broad use of scfvs is confined by their generally low stability. ...201222484084
molecular double-check strategy for the identification and characterization of european lyssaviruses.the "gold standard" for post-mortem rabies diagnosis is the direct fluorescent antibody test (fat). however, in the case of ante-mortem non-neural sample material or decomposed tissues, the fat reaches its limit, and the use of molecular techniques can be advantageous. in this study, we developed and validated a reverse transcription pcr cascade protocol feasible for the classification of samples, even those for which there is no epidemiological background knowledge. this study emphasises on the ...201424681051
favourable outcome in a patient bitten by a rabid bat infected with the european bat lyssavirus-1.the classic rabies virus (genotype 1) has been eliminated in western europe, but related lyssaviruses still circulate in local bats. in august 2010, a belgian photographer was bitten upon provocation of a disoriented eptesicus serotinus bat in spain. the bat was infected with european bat lyssavirus-1 (genotype 5). the isolate proved highly neurovirulent in mice. the patient had received preventive rabies immunisations years before the incident and received two boosters with the hdcv rabies vacc ...201623627196
a step forward in molecular diagnostics of lyssaviruses--results of a ring trial among european laboratories.rabies is a lethal and notifiable zoonotic disease for which diagnostics have to meet the highest standards. in recent years, an evolution was especially seen in molecular diagnostics with a wide variety of different detection methods published. therefore, a first international ring trial specifically designed on the use of reverse transcription polymerase chain reaction (rt-pcr) for detection of lyssavirus genomic rna was organized. the trial focussed on assessment and comparison of the perform ...201323520505
membrane and inclusion body targeting of lyssavirus matrix proteins.lyssavirus matrix proteins (m) support virus budding and have accessory functions that may contribute to host cell manipulation and adaptation to specific hosts. here, we show that rabies virus (rabv) and european bat lyssavirus type 1 (eblv-1) m proteins differ in targeting and accumulation at cellular membranes. in contrast to rabv m, eblv-1 m expressed from authentic eblv-1 or chimeric rabv accumulated at the golgi apparatus. chimeric m proteins revealed that golgi association depends on the ...201323046288
antibody response to vaccines for rhinotracheitis, caliciviral disease, panleukopenia, feline leukemia, and rabies in tigers (panthera tigris) and lions (panthera leo).this article presents the results of a study of captive tigers (panthera tigris) and lions (panthera leo) vaccinated with a recombinant vaccine against feline leukemia virus; an inactivated adjuvanted vaccine against rabies virus; and a multivalent modified live vaccine against feline herpesvirus, calicivirus, and panleukopenia virus. the aim of the study was to assess the immune response and safety of the vaccines and to compare the effects of the administration of single (1 ml) and double (2 m ...201222779227
tail vaccination in cats: a pilot study.feline injection site sarcomas affect 1-10 cats per every 10,000 vaccinated and are associated with high mortality. radical resection may be curative, but is often associated with prolonged recovery, disfigurement and loss of function when tumors occur at currently recommended injection sites. the objective of this study was to assess alternatives to currently recommended vaccination sites in terms of preference by oncology practitioners, ease of injection and serological responses. surgical, ra ...201424108201
rhabdovirus-based vaccine platforms against henipaviruses.the emerging zoonotic pathogens hendra virus (hev) and nipah virus (niv) are in the genus henipavirus in the family paramyxoviridae. hev and niv infections can be highly fatal to humans and livestock. the goal of this study was to develop candidate vaccines against henipaviruses utilizing two well-established rhabdoviral vaccine vector platforms, recombinant rabies virus (rabv) and recombinant vesicular stomatitis virus (vsv), expressing either the codon-optimized or the wild-type (wt) hev glyco ...201525320306
european bats as carriers of viruses with zoonotic potential.bats are being increasingly recognized as reservoir hosts of highly pathogenic and zoonotic emerging viruses (marburg virus, nipah virus, hendra virus, rabies virus, and coronaviruses). while numerous studies have focused on the mentioned highly human-pathogenic bat viruses in tropical regions, little is known on similar human-pathogenic viruses that may be present in european bats. although novel viruses are being detected, their zoonotic potential remains unclear unless further studies are con ...201425123684
public health ethics and more-than-human solidarity.this article contributes to the literature on one health and public health ethics by expanding the principle of solidarity. we conceptualise solidarity to encompass not only practices intended to assist other people, but also practices intended to assist non-human others, including animals, plants, or places. to illustrate how manifestations of humanist and more-than-human solidarity may selectively complement one another, or collide, recent responses to hendra virus in australia and rabies viru ...201524919648
biochemical and structural studies of the oligomerization domain of the nipah virus phosphoprotein: evidence for an elongated coiled-coil homotrimer.nipah virus (niv) is a recently emerged severe human pathogen that belongs to the henipavirus genus within the paramyxoviridae family. the niv genome is encapsidated by the nucleoprotein (n) within a helical nucleocapsid that is the substrate used by the polymerase for transcription and replication. the polymerase is recruited onto the nucleocapsid via its cofactor, the phosphoprotein (p). the niv p protein has a modular organization, with alternating disordered and ordered domains. among these ...201324074578
transmission of viral disease to the recipient through the donor liver.morbidity and mortality after liver transplantation continue to be significantly influenced by infectious complications. a particular concern is transmission of pathogens through the graft, which may cause significant disease in the recipient.200727711010
hierarchically self-organized monolithic nanoporous membrane for excellent virus enrichment.enrichment of viruses is essential for making high dose viral stocks for vaccines and virus-related research. since the widely used ultracentrifugation for concentrating viral stock requires ultra-high speed rotation, it easily destroys the activity of some viruses, for instance, hepatitis c virus (hcv), which has a fragile structure and low virus titer. we introduce a novel method to concentrate hcv virus in stock by using a hierarchically self-organized monolithic nanoporous membrane made by s ...201424354273
aptamer-based therapeutics: new approaches to combat human viral diseases.viruses replicate inside the cells of an organism and continuously evolve to contend with an ever-changing environment. many life-threatening diseases, such as aids, sars, hepatitis and some cancers, are caused by viruses. because viruses have small genome sizes and high mutability, there is currently a lack of and an urgent need for effective treatment for many viral pathogens. one approach that has recently received much attention is aptamer-based therapeutics. aptamer technology has high targ ...201324287493
application of recombinant adenoviruses expressing glycoprotein or nucleoprotein of rabies virus to korean raccoon dogs.a new rabies vaccine for animals, including raccoon dogs, in korea is needed to eradicate rabies infection. in this study, we constructed two recombinant adenoviruses expressing the glycoprotein or nucleoprotein of the rabies virus (rabv). we then investigated the safety and immunogenicity of these strains in raccoon dogs, depending on inoculation route.201526273578
glycoprotein from street rabies virus bd06 induces early and robust immune responses when expressed from a non-replicative adenovirus recombinant.the rabies virus (rabv) glycoprotein (g) is responsible for inducing neutralizing antibodies against rabies virus. development of recombinant vaccines using the g genes from attenuated strains rather than street viruses is a regular practice. in contrast to this scenario, we generated three human adenovirus type 5 recombinants using the g genes from the vaccine strains srv9 and flury-lep, and the street rabv strain bd06 (nrad5-srv9-g, nrad5-flury-lep-g, and nrad5-bd06-g). these recombinants were ...201526143474
human contacts with oral rabies vaccine baits distributed for wildlife rabies management--ohio, 2012.baits laden with oral rabies vaccines are important for the management of wildlife rabies in the united states. in august 2012, the wildlife services program of the u.s. department of agriculture's animal and plant health inspection service began a field trial involving limited distribution of a new oral rabies vaccine bait in five states, including ohio. the vaccine consisted of live recombinant human adenovirus type 5 vector, expressing rabies virus glycoprotein (adrg1.3) (onrab). a previously ...201323575240
[guidelines for antifungal prophylaxis, diagnosis and therapy in pediatric hematology and oncology - a review of literature and expert recommendations].problems with importing non-registered medicines for treating rare life-threatening infectious diseases led to establishment of the emergency anti-infective drug reserve (eaidr) for the czech republic.201425702289
viruses, apoptosis, and neuroinflammation--a double-edged sword.apoptosis, or programmed cell death, is a fundamental and widespread cell biological process that is distinct from cell necrosis and can be induced by a wide variety of stimuli including viral infections. apoptosis may occur via either the intrinsic or extrinsic pathways and confers several advantages to the virally infected host including the prevention of further viral propagation and the potential inhibition and resolution of inflammatory processes. several viruses have been shown to have the ...201525604493
[emergency reserve of life-saving anti-infective drugs].problems with importing non-registered medicines for treating rare life-threatening infectious diseases led to establishment of the emergency anti-infective drug reserve (eaidr) for the czech republic.201425135139
[viral superantigens].superantigens (sags) are microbial proteins produced by various microorganisms that elicit excessive and strong stimulation of t cells via an unconventional mechanism. they cause polyclonal activation of t cells in a non-specific manner, by binding to a particular variable-beta (vβ) chain of t-cell receptor (tcr) and mhc class ii molecule, in unprocessed form and outside of peptide-binding cleft, forming a bridge between the antigen presenting cell and the t cell. sags are classified into three ...201627525406
a bivalent, chimeric rabies virus expressing simian immunodeficiency virus envelope induces multifunctional antibody responses.we previously showed that a matrix (m) gene-deleted rabies virus (rabv)-based vaccine (rabv-δm) is highly immunogenic and induces potent b cell responses in the context of rabv infection. we speculated that rabv-δm expressing hiv proteins would also induce potent b cell responses against hiv antigens. as a prerequisite to future studies in nonhuman primates, we completed immunogenicity studies in mice to confirm the ability of rabv-δm to induce polyfunctional b cell responses in the context of h ...201525848984
biochemical features and antiviral activity of a monomeric catalytic antibody light-chain 23d4 against influenza a virus.catalytic antibodies have exhibited interesting functions against some infectious viruses such as hiv, rabies virus, and influenza virus in vitro as well as in vivo. in some cases, a catalytic antibody light chain takes on several structures from the standpoint of molecular size (monomer, dimer, etc.) and/or isoelectronic point. in this study, we prepared a monomeric 23d4 light chain by mutating the c-terminal cys to ala of the wild-type. the mutated 23d4 molecule took a simple monomeric form, w ...201525713031
improved transduction efficiency of a lentiviral vector for neuron-specific retrograde gene transfer by optimizing the junction of fusion envelope glycoprotein.the vector for neuron-specific retrograde gene transfer (neuret) is a pseudotype of human immunodeficiency virus type 1 (hiv-1)-based vector with fusion glycoprotein type c (fug-c), which consists of the n-terminal region of the extracellular domain of rabies virus glycoprotein (rvg) and the membrane-proximal region of the extracellular domain and the transmembrane/cytoplasmic domains of vesicular stomatitis virus glycoprotein (vsvg). the neuret vector shows a high efficiency of gene transfer th ...201424613797
highly efficient retrograde gene transfer into motor neurons by a lentiviral vector pseudotyped with fusion glycoprotein.the development of gene therapy techniques to introduce transgenes that promote neuronal survival and protection provides effective therapeutic approaches for neurological and neurodegenerative diseases. intramuscular injection of adenoviral and adeno-associated viral vectors, as well as lentiviral vectors pseudotyped with rabies virus glycoprotein (rv-g), permits gene delivery into motor neurons in animal models for motor neuron diseases. recently, we developed a vector with highly efficient re ...201324086660
comparison of heterologous prime-boost strategies against human immunodeficiency virus type 1 gag using negative stranded rna viruses.this study analyzed a heterologous prime-boost vaccine approach against hiv-1 using three different antigenically unrelated negative-stranded viruses (nsv) expressing hiv-1 gag as vaccine vectors: rabies virus (rabv), vesicular stomatitis virus (vsv) and newcastle disease virus (ndv). we hypothesized that this approach would result in more robust cellular immune responses than those achieved with the use of any of the vaccines alone in a homologous prime-boost regimen. to this end, we primed bal ...201323840600
antiretroviral therapy interruptions result in loss of protective humoral immunity to neoantigens in hiv-infected individuals.sustained antiretroviral therapy (art)-mediated viral suppression restores responses to vaccination in hiv-1-infected individuals. as art interruption occur frequently in resource-constrained settings, we studied their effects on the ability to mount humoral immune responses against a neoantigen.201222516873
a role for granulocyte-macrophage colony-stimulating factor in the regulation of cd8(+) t cell responses to rabies virus.inflammatory cytokines have a significant role in altering the innate and adaptive arms of immune responses. here, we analyzed the effect of gm-csf on a rabv-vaccine vector co-expressing hiv-1 gag. to this end, we immunized mice with rabv expressing hiv-1 gag and gm-csf and analyzed the primary and recall cd8(+) t cell responses. we observed a statistically significant increase in antigen presenting cells (apcs) in the spleen and draining lymph nodes in response to gm-csf. despite the increase i ...201222341782
rabies and rabies virus in wildlife in mainland china, 1990-2013.the number of wildlife rabies and wildlife-associated human and livestock rabies cases has increased in recent years, particularly in the southeast and northeast regions of mainland china. to better understand wildlife rabies and its role in human and livestock rabies, we reviewed what is known about wildlife rabies from the 1990s to 2013 in mainland china. in addition, the genetic diversity and phylogeny of available wildlife-originated rabies viruses (rabvs) were analyzed. several wildlife spe ...201424911887
early diagnosis of irkut virus infection using magnetic bead-based serum peptide profiling by maldi-tof ms in a mouse model.early diagnosis is important for the prompt post-exposure prophylaxis of lyssavirus infections. to diagnose irkut virus (irkv) infection during incubation in mice, a novel method using magnetic bead-based serum peptide profiling by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (maldi-tof ms) has been established. for this test, serum peptides were concentrated by adsorption to and elution from the magnetic bead-based weak cation ion exchanger. mass spectrograms obt ...201424670473
evaluation of rabies biologics against irkut virus isolated in china.an irkut virus (irkv) was recently isolated from a bat in china. the protective ability of rabies biologics available in the chinese market and experimental biologics against the rabies virus (rabv) and irkv were assessed in a hamster model via preexposure prophylaxis (prep) and postexposure prophylaxis (pep) experiments. the results demonstrated that a single dose of rabies vaccine did not induce adequate protection against irkv infection. however, routine prep with three doses of vaccine induc ...201323946522
isolation of irkut virus from a murina leucogaster bat in china.bats are recognized as a major reservoir of lyssaviruses; however, no bat lyssavirus has been isolated in asia except for aravan and khujand virus in central asia. all chinese lyssavirus isolates in previous reports have been of species rabies virus, mainly from dogs. following at least two recent bat-associated human rabies-like cases in northeast china, we have initiated a study of the prevalence of lyssaviruses in bats in jilin province and their public health implications. a bat lyssavirus h ...201323505588
the yin and yang of antiviral innate immunity in central nervous system.the innate immune system provides protection against invading neurotropic viruses. it acts as the first line of defense against invading viruses and plays an elementary role in their pathogenesis. the list of viruses capable of infecting human central nervous system (cns) is quite long, most important of them are japanese encephalitis virus (jev), rabies virus, west nile virus (wnv), herpes simplex virus (hsv), st. louis encephalitis virus (slev), la crosse virus, tick borne encephalitis virus ( ...201626635264
endemic lagos bat virus infection in eidolon helvum.phylogenetic analyses suggest lyssaviruses, including rabies virus, originated from bats. however, the role of bats in the maintenance, transmission and evolution of lyssaviruses is poorly understood. a number of genetically diverse lyssaviruses are present in africa, including lagos bat virus (lbv). a high seroprevalence of antibodies against lbv was detected in eidolon helvum bats. longitudinal seroprevalence and age-specific seroprevalence data were analysed and capture-mark-recapture (cmr) a ...201222370126
raccoonpoxvirus safety in immunocompromised and pregnant mouse models.numerous poxviruses infect humans and animal hosts, and a poxvirus vaccine with an improved safety profile is needed as the current vaccinia virus vaccine is contraindicated in individuals that have a history of eczema or heart disease, or are immunocompromised or pregnant. in addition, poxviruses make excellent vaccine vectors for other infectious diseases and cancer. raccoonpoxvirus is a naturally occurring attenuated north american poxvirus, and thus it is of interest as a vaccine vector plat ...201424837508
[investigation of adenovirus isolation frequency from the stool samples of patients suspected with acute flaccid paralysis].although adenoviruses (advs) generally cause upper respiratory tract infections, conjunctivitis/epidemic keratoconjunctivitis, gastroenteritis and pneumonia, they can lead to the involvement of central nervous system. acute flaccid paralysis (afp) is a type of seizure, characterized by rapid and sudden onset of extreme weakness in hands and feet, including (less frequently) weakness of respiratory and swallowing, representing with decreased muscle tone, especially in children below 15-year-old. ...201627175501
chimeric rabies glycoprotein with a transmembrane domain and cytoplasmic tail from newcastle disease virus fusion protein incorporates into the newcastle disease virion at reduced levels.rabies is still an important world-wide health problem. newcastle disease virus (ndv) has been developed as a vaccine vector in animals using a reverse genetics system. previously, our group generated a recombinant ndv (lasota strain) expressing the complete rabies g protein (rvg), named rl-rvg. in this study, we constructed a variant, rl-rvgtm, which expresses a chimeric rabies g protein rvgtm containing the ectodomain of rvg and the transmembrane domain(tm) and cytoplasmic tail (ct) from the n ...201627515260
recombinant newcastle disease virus (rl-rvg) triggers autophagy and apoptosis in gastric carcinoma cells by inducing er stress.we have reported that the recombinant avirulent newcastle disease virus (ndv) lasota strain expressing the rabies virus glycoprotein (rl-rvg) could induce autophagy and apoptosis in gastric carcinoma cells. in the present study, we explored the upstream regulators, endoplasmic reticulum (er) stress that induce autophagy and apoptosis and the relationships among them. for this purpose, sgc-7901 and hgc cells were infected with rl-rvg. ndv lasota strain and phosphate-buffered saline (pbs) were tre ...201627293989
autophagy is involved in recombinant newcastle disease virus (rl-rvg)-induced cell death of stomach adenocarcinoma cells in vitro.oncolytic viruses can kill malignant cells while sparing normal cells. multiple pathways are involved in this action. the antitumor effects of viral infection on sgc-7901 and ags cells were investigated. we measured endoplasmic reticulum stress and autophagy caused by the recombinant avirulent newcastle disease virus (ndv) lasota strain expressing the rabies virus glycoprotein (rl-rvg) and the ndv wild-type strain. the dose-response curves were analyzed using the mtt assay. the expression of rvg ...201526058483
apoptotic induction of lung adenocarcinoma a549 cells infected by recombinant rvg newcastle disease virus (rl-rvg) in vitro.newcastle disease virus (ndv) is a member of the genus avulavirus in the paramyxoviridae family and its antitumor properties depend on its ability to kill malignant cells while not affecting normal cells. the present study investigated a recombinant avirulent ndv lasota strain (wild-type ndv strain) expressing the rabies virus glycoprotein (rl-rvg), examined its oncolytic effect on the lung adenocarcinoma a549 cell line and evaluated its potential to serve as a vaccine against lung cancer. a549 ...201525322856
[rl-rvg inhibits proliferation and promotes apoptosis of lung cancer cells in vitro].to infect lung adenocarcinoma a549 cells with recombinant lasota strain newcastle disease virus (ndv) vaccine expressing the rabies virus glycoprotein (rl-rvg), and explore the effect of rl-rvg on proliferation and apoptosis of lung cancer cells.201424796735
roles of nuclear trafficking in infection by cytoplasmic negative-strand rna viruses: paramyxoviruses and beyond.genome replication and virion production by most negative-sense rna viruses (nsvs) occurs exclusively in the cytoplasm, but many nsv-expressed proteins undergo active nucleocytoplasmic trafficking via signals that exploit cellular nuclear transport pathways. nuclear trafficking has been reported both for nsv accessory proteins (including isoforms of the rabies virus phosphoprotein, and v, w and c proteins of paramyxoviruses) and for structural proteins. trafficking of the former is thought to en ...201627498841
immunology of bats and their viruses: challenges and opportunities.bats are reservoir hosts of several high-impact viruses that cause significant human diseases, including nipah virus, marburg virus and rabies virus. they also harbor many other viruses that are thought to have caused disease in humans after spillover into intermediate hosts, including sars and mers coronaviruses. as is usual with reservoir hosts, these viruses apparently cause little or no pathology in bats. despite the importance of bats as reservoir hosts of zoonotic and potentially zoonotic ...201425494448
[not available].important preventive measures carried out in the herds of domestic animals have found improving the health status of farms, particularly for contagious diseases subject to mandatory declaration and accompanying drastic but necessary eradication measures in infected flocks. however it is more difficult to apply these same biosecurity measures on wildlife that may have been contaminated or not by domestic animals. the growing number of emerging infectious diseases of wildlife may reflect increased ...201427120911
parainfluenza virus 5 expressing the g protein of rabies virus protects mice after rabies virus infection.rabies remains a major public health threat around the world. once symptoms appear, there is no effective treatment to prevent death. in this work, we tested a recombinant parainfluenza virus 5 (piv5) strain expressing the glycoprotein (g) of rabies (piv5-g) as a therapy for rabies virus infection: we have found that piv5-g protected mice as late as 6 days after rabies virus infection. piv5-g is a promising vaccine for prevention and treatment of rabies virus infection.201525552723
pseudo-typed semliki forest virus delivers egfp into neurons.semliki forest virus (sfv), a neurotropic virus, has been used to deliver heterologous genes into cells in vitro and in vivo. in this study, we constructed a reporter sfv4-fl-egfp and found that it can deliver egfp into neurons located at the injection site without disseminating throughout the brain. lacking of the capsid gene of sfv4-fl-egfp does not block its life cycle, while forming replication-competent virus-like particles (vlps). these vlps hold subviral genome by using the packaging sequ ...201727739033
rabies virus glycoprotein and immune response pattern using recombinant protein or recombinant rna viral vectors.the present study shows the humoral and cellular aspects of immune response generated by a recombinant rabies virus glycoprotein (rrvgp) as compared to those generated by viral vector carrying the rna coding for this protein (rvgp-rna). the rrvgp was synthesized by stably transfected drosophila melanogaster schneider 2 (s2) cells and the rvgp-rna was carried by a recombinant semiliki forest virus (sfv-rvgp). the data show that protein as well as the rna vaccine was capable of inducing reasonably ...201424598721
quantitative rt-pcr for titration of replication-defective recombinant semliki forest virus.virus titration may constitute a drawback in the development and use of replication-defective viral vectors like semliki forest virus (sfv). the standardization and validation of a reverse transcription quantitative pcr (qrt-pcr) method for sfv titration is presented here. the qrt-pcr target is located within the nsp1 gene of the non-structural polyprotein sfv region (sfv rna), which allows the strategy to be used for several different recombinant sfv constructs. titer determinations were carrie ...201323933080
rabies viruses leader rna interacts with host hsc70 and inhibits virus replication.viruses have been shown to be equipped with regulatory rnas to evade host defense system. it has long been known that rabies virus (rabv) transcribes a small regulatory rna, leader rna (lerna), which mediates the transition from viral rna transcription to replication. however, the detailed molecular mechanism remains enigmatic. in the present study, we determined the genetic architecture of rabv lerna and demonstrated its inhibitory effect on replication of wild-type rabies, drv-ah08. the rna im ...201728388579
successful strategies implemented towards the elimination of canine rabies in the western hemisphere.almost all cases of human rabies result from dog bites, making the elimination of canine rabies a global priority. during recent decades, many countries in the western hemisphere have carried out large-scale dog vaccination campaigns, controlled their free-ranging dog populations and enforced legislation for responsible pet ownership. this article reviews progress in eliminating canine rabies from the western hemisphere. after briefly summarizing the history of control efforts and describing the ...201728385500
the history of rabies in the western hemisphere.before the introduction of control programs in the 20th century, rabies in domestic dogs occurred throughout the western hemisphere. however, historical records and phylogenetic analysis of multiple virus isolates indicate that, before the arrival of the first european colonizers, rabies virus was likely present only in bats and skunks. canine rabies was either rare or absent among domestic dogs of native americans, and first arrived when many new dog breeds were imported during the period of eu ...201728365457
status of laboratory biosafety and biosecurity in veterinary research facilities in nigeria.this study determined current status of laboratory biosafety in nigerian veterinary research facilities.201728344841
a dna logic gate automaton for detection of rabies and other lyssaviruses.immediate activation of biosensors is not always desirable, particularly if activation is due to non-specific interactions. here we demonstrate the use of deoxyribozyme-based logic gate networks arranged into visual displays to precisely control activation of biosensors, and demonstrate a prototype molecular automaton able to discriminate between seven different genotypes of lyssaviruses, including rabies virus. the device uses novel mixed-base logic gates to enable detection of the large divers ...201728342196
a permanent host shift of rabies virus from chiroptera to carnivora associated with recombination.bat virus host shifts can result in the spread of diseases with significant effects. the rabies virus (rabv) is able to infect almost all mammals and is therefore a useful model for the study of host shift mechanisms. carnivore rabvs originated from two historical host shifts from bat viruses. to reveal the genetic pathways by which bat rabvs changed their host tropism from bats to carnivores, we investigated the second permanent bat-to-carnivore shift resulting in two carnivore variants, known ...201728325933
ecological niche modeling of rabies in the changing arctic of alaska.rabies is a disease of global significance including in the circumpolar arctic. in alaska enzootic rabies persist in northern and western coastal areas. only sporadic cases have occurred in areas outside of the regions considered enzootic for the virus, such as the interior of the state and urbanized regions.201728320440
engineering a growth sensor to select intracellular antibodies in the cytosol of mammalian cells.intracellular antibodies (intrabodies) are expected to function as therapeutics as well as tools for elucidating in vivo function of proteins. in this study, we propose a novel intrabody selection method in the cytosol of mammalian cells by utilizing a growth signal, induced by the interaction of the target antigen and an scfv-c-kit growth sensor. here, we challenge this method to select specific intrabodies against rabies virus nucleoprotein (rv-n) for the first time. as a result, we successful ...201728319021
barriers to innovation in human rabies prophylaxis and treatment: a causal analysis of insights from key opinion leaders and literature.rabies is an essentially 100% fatal, zoonotic disease, caused by lyssaviruses. currently, the disease is vaccine-preventable with pre- and post-exposure prophylaxis (prep and pep). still, rabies virus is estimated to cause up to 60,000 human deaths annually, of which the vast majority occurs in rural asia and africa, due to the inaccessibility of prophylaxis and non-existence of treatment. despite these unmet clinical needs, rabies control mainly focuses on the sylvatic reservoir and drug innova ...201728318148
safety, tolerability and efficacy of intradermal rabies immunization with debioject™.in a single-center study, 66 healthy volunteers aged between 18 and 50years were randomized to be immunized against rabies with three different injection routes: intradermal with debioject™ (idj), standard intradermal with classical needle (ids), also called mantoux method, and intramuscular with classical needle (im). "vaccin rabique pasteur®" and saline solution (nacl 0.9%) were administered at d0, d7 and d28. antigen doses for both intradermal routes were 1/5 of the dose for im. tolerability, ...201728317660
correction to: huey, rachel, hawthorne, susan, the potential use of rabies virus glycoprotein-derived peptides to facilitate drug delivery into the central nervous system: a mini review. 201728316247
barriers to dog rabies vaccination during an urban rabies outbreak: qualitative findings from arequipa, peru.canine rabies was reintroduced to the city of arequipa, peru in march 2015. the ministry of health has conducted a series of mass dog vaccination campaigns to contain the outbreak, but canine rabies virus transmission continues in arequipa's complex urban environment, putting the city's 1 million inhabitants at risk of infection. the proximate driver of canine rabies in arequipa is low dog vaccination coverage. our objectives were to qualitatively assess barriers to and facilitators of rabies va ...201728306717
management and modeling approaches for controlling raccoon rabies: the road to elimination.rabies is an ancient viral disease that significantly impacts human and animal health throughout the world. in the developing parts of the world, dog bites represent the highest risk of rabies infection to people, livestock, and other animals. however, in north america, where several rabies virus variants currently circulate in wildlife, human contact with the raccoon rabies variant leads to the highest per capita population administration of post-exposure prophylaxis (pep) annually. previous ra ...201728301480
lyssaviruses and rabies: current conundrums, concerns, contradictions and controversies.lyssaviruses are bullet-shaped, single-stranded, negative-sense rna viruses and the causative agents of the ancient zoonosis rabies. africa is the likely home to the ancestors of taxa residing within the genus lyssavirus, family rhabdoviridae. diverse lyssaviruses are envisioned as co-evolving with bats, as the ultimate reservoirs, over seemingly millions of years. in terms of relative distribution, overt abundance, and resulting progeny, rabies virus is the most successful lyssavirus species to ...201728299201
disynaptic subthalamic input to the posterior cerebellum in rat.in the last decade, the interplay between basal ganglia and cerebellar functions has been increasingly advocated to explain their joint operation in both normal and pathological conditions. yet, insight into the neuroanatomical basis of this interplay between both subcortical structures remains sparse and is mainly derived from work in primates. here, in rodents, we have studied the existence of a potential disynaptic connection between the subthalamic nucleus (stn) and the cerebellar cortex as ...201728293179
large-scale reconstructions and independent, unbiased clustering based on morphological metrics to classify neurons in selective populations.this protocol outlines large-scale reconstructions of neurons combined with the use of independent and unbiased clustering analyses to create a comprehensive survey of the morphological characteristics observed among a selective neuronal population. combination of these techniques constitutes a novel approach for the collection and analysis of neuroanatomical data. together, these techniques enable large-scale, and therefore more comprehensive, sampling of selective neuronal populations and esta ...201728287546
impact of caspase-1/11, -3, -7, or il-1β/il-18 deficiency on rabies virus-induced macrophage cell death and onset of disease.rabies virus is a highly neurovirulent rna virus, which causes about 59000 deaths in humans each year. previously, we described macrophage cytotoxicity upon infection with rabies virus. here we examined the type of cell death and the role of specific caspases in cell death and disease development upon infection with two laboratory strains of rabies virus: challenge virus standard strain-11 (cvs-11) is highly neurotropic and lethal for mice, while the attenuated evelyn-rotnycki-abelseth (era) str ...201728280602
enhanced transport of plant-produced rabies single chain antibody-rvg peptide fusion protein across an in cellulo blood-brain barrier device.the biomedical applications of antibody engineering are developing rapidly and have been expanded to plant expression platforms. in the present study, we have generated a novel antibody molecule in planta for targeted delivery across the blood-brain barrier (bbb). rabies virus (rabv) is a neurotropic virus for which there is no effective treatment after entry into the central nervous system (cns). this study investigated the use of a rabv glycoprotein peptide sequence to assist delivery of a rab ...201728273388
alum adjuvanted rabies dna vaccine confers 80% protection against lethal 50 ld50 rabies challenge virus standard strain.rabies is a serious concern world-wide. despite availability of rabies vaccines for long; their efficacy, safety, availability and cost effectiveness has been a tremendous issue. this calls for improvement of rabies vaccination strategies. dna vaccination has immense potential in this regard. the dna vaccine pgp.lamp-1 conferred 60% protection to balb/c mice against 20 ld50 rabies challenge virus standard (cvs) strain challenge. upon supplementation with emulsigen-d, the vaccine formulation conf ...201728267643
elimination of dog-mediated human rabies deaths by 2030: needs assessment and alternatives for progress based on dog vaccination.rabies imposes a substantial burden to about half of the world population. the world health organization (who), world organization for animal health, and the food and agriculture organization have set the goal of eliminating dog-mediated human rabies deaths by 2030. this could be achieved largely by massive administration of post-exposure prophylaxis-in perpetuity-, through elimination of dog rabies, or combining both. here, we focused on the resources needed for the elimination of dog rabies vi ...201728239608
serological evidence of lyssavirus infection among bats in nagaland, a north-eastern state in india.bats are known to be reservoirs of several medically important viruses including lyssaviruses. however, no systematic surveillance for bat rabies has been carried out in india, a canine rabies endemic country with a high burden of human rabies. surveillance for rabies virus (rabv) infection in bats was therefore carried out in nagaland, a north-eastern state in india at sites with intense human-bat interfaces during traditional bat harvests. brain tissues and sera from bats were tested for evide ...201728228179
the control of eye movements by the cerebellar nuclei: polysynaptic projections from the fastigial, interpositus posterior and dentate nuclei to lateral rectus motoneurons in primates.premotor circuits driving extraocular motoneurons and downstream motor outputs of cerebellar nuclei are well known. however, there is, as yet, no unequivocal account of cerebellar output pathways controlling eye movements in primates. using retrograde transneuronal transfer of rabies virus from the lateral rectus (lr) eye muscle, we studied polysynaptic pathways to lr motoneurons in primates. injections were placed either into the central or distal muscle portion, to identify innervation differe ...201728226411
the phylodynamics of the rabies virus in the russian federation.near complete rabies virus n gene sequences (1,110 nt) were determined for 82 isolates obtained from different regions of russia between 2008 and 2016. these sequences were analyzed together with 108 representative genbank sequences from 1977-2016 using the bayesian coalescent approach. the timing of the major evolutionary events was estimated. most of the isolates represented the steppe rabies virus group c, which was found over a vast geographic region from central russia to mongolia and split ...201728225771
short interfering rnas targeting a vampire-bat related rabies virus phosphoprotein mrna.the aim of this study was to assess the in vitro and in vivo effects of short-interfering rnas (sirnas) against rabies virus phosphoprotein (p) mrna in a post-infection treatment for rabies as an extension of a previous report (braz j microbiol. 2013 nov 15;44(3):879-82). to this end, rabies virus strain rabv-4005 (related to the desmodus rotundus vampire bat) were used to inoculate bhk-21 cells and mice, and the transfection with each of the sirnas was made with lipofectamine-2000™. in vitro re ...201728223028
application of high-throughput sequencing to whole rabies viral genome characterisation and its use for phylogenetic re-evaluation of a raccoon strain incursion into the province of ontario.raccoon rabies remains a serious public health problem throughout much of the eastern seaboard of north america due to the urban nature of the reservoir host and the many challenges inherent in multi-jurisdictional efforts to administer co-ordinated and comprehensive wildlife rabies control programmes. better understanding of the mechanisms of spread of rabies virus can play a significant role in guiding such control efforts. to facilitate a detailed molecular epidemiological study of raccoon ra ...201728219746
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
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