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addition of c3d-p28 adjuvant to a rabies dna vaccine encoding the g5 linear epitope enhances the humoral immune response and confers protection.rabies dna vaccines based on full-length glycoprotein (g) induce virus neutralizing antibody (vna) responses and protect against the virus challenge. although conformational epitopes of g are the main target of vnas, some studies have shown that a polypeptide linear epitope g5 is also able to induce vnas. however, a g5 dna vaccine has not been explored. while multiple doses of dna vaccines are required in order to confer a protective immune response, this could be overcome by the inclusion of c3 ...201829191739
immunogenic response in obese patients undergoing rabies post-exposure prophylaxis with combined equine rabies immunoglobulin and rabies vaccination.obesity is a risk factor for increased morbidity and mortality associated with many vaccine preventable infectious diseases such as influenza. moreover, higher volume of passive rabies immunoglobulin (rig) due to weight based dosing might suppress vaccine-induced immune responses in obese patients. this study aimed to evaluate the effect of obesity on humoral immune responses to combined equine rig and rabies vaccine treatment among patients with who category iii exposure to a rabies suspected a ...201829191737
the lyssavirus host-specificity conundrum-rabies virus-the exception not the rule.lyssaviruses are a diverse range of viruses which all cause the disease rabies. of the 16 recognized species, only rabies viruses (rabv) have multiple host reservoirs. although lyssaviruses are capable of infecting all mammals, onward transmission in a new host population requires adaptation of the virus, in a number of stages with both host and virus factors determining the outcome. due to an absence of recorded non-rabv host shifts, rabv data is extrapolated to draw conclusions for all lyssavi ...201729182939
a phase ii randomized study to determine the safety and immunogenicity of the novel pika rabies vaccine containing the pika adjuvant using an accelerated regimen.human rabies infection continues to be potentially fatal despite the availability of post-exposure prophylaxis with rabies vaccine. the pika rabies vaccine adjuvant is a tlr3 agonist and has been shown to be safe and immunogenic in clinical phase i studies.201729174316
the effect of selected molecules influencing the detrimental host immune response on a course of rabies virus infection in a murine model.rabies is invariably fatal, when post-exposure prophylaxis is administered after the onset of clinical symptoms. in many countries, rabies awareness is very low and the availability of post-exposure prophylaxis, as recommended by who guidelines, is very limited or non-existent, probably as a consequence of high cost. therefore, new concepts for rabies therapy are needed. innate immune mechanisms involving the production of pro-inflammatory cytokines and chemokines, activated after rabies infecti ...201729153584
vaccination of ferrets for rabies and distemper.companion ferrets need to be vaccinated against 2 viral diseases that cause neurologic illness: canine distemper and rabies. although not common in ferrets, both viruses are fatal in ferrets and rabies virus is also fatal in humans. in this article, we provide a basic review of the 2 diseases, highlighting key neurologic concerns. we also review and update current vaccine concerns from a practitioner's perspective, including available vaccines, vaccine schedule recommendations, vaccine reactions ...201829146026
structure and assembly of the ebola virus nucleocapsid.ebola and marburg viruses are filoviruses: filamentous, enveloped viruses that cause haemorrhagic fever. filoviruses are within the order mononegavirales, which also includes rabies virus, measles virus, and respiratory syncytial virus. mononegaviruses have non-segmented, single-stranded negative-sense rna genomes that are encapsidated by nucleoprotein and other viral proteins to form a helical nucleocapsid. the nucleocapsid acts as a scaffold for virus assembly and as a template for genome tran ...201729144446
an optimized hmgb1 expressed by recombinant rabies virus enhances immunogenicity through activation of dendritic cells in mice.rabies remains an important public health threat, killing approximately 59,000 people worldwide annually, most of which are from the developing countries of africa and asia where dog rabies are endemic. therefore, developing an affordable and efficacious vaccine for dog-mediated rabies control is needful in these countries. our previous studies indicated that over-expression of granulocyte-macrophage colony stimulating factor (gm-csf) or macrophage inflammatory protein-1 (mip-1α or ccl3) by reco ...201729137362
re-evaluating the effect of favipiravir treatment on rabies virus infection.there is no antiviral treatment available once clinical disease following rabies virus infection has initiated. considered a neglected tropical disease, >60,000 human rabies deaths are estimated each year despite the availability of pre- and post-exposure prophylaxis for pre-immunisation or administration following a potential exposure before the onset of clinical disease. such post-exposure treatments include administration of rabies immunoglobulin (rig) and vaccination at a distant site to pri ...201729132993
infection of neuroblastoma cells by rabies virus is modulated by the virus titer.rabies is a lethal viral infection that can affect almost all mammals, including humans. to better understand the replication of rabies lyssavirus, we investigated if the viral load in brains naturally infected with rabies influences viral internalization and viral growth kinetics in neuroblastoma cells, and if the viral load affects mortality in mice after intradermal infection. we noted that high initial viral loads in brains (group ii) were unfavourable for increasing viral titers during seri ...201829122670
development of molecular and cellular tools to decipher the type i ifn pathway of the common vampire bat.though the common vampire bat, desmodus rotundus, is known as the main rabies virus reservoir in latin america, no tools are available to investigate its antiviral innate immune system. to characterize the ifn-i pathway, we established an immortalized cell line from a d. rotundus fetal lung named fludero. then we molecularly characterized some of the toll-like receptors (tlr3, 7, 8 and 9), the three rig-i-like receptor members, as well as ifnα1 and ifnβ. challenging the fludero cell line with po ...201829122634
a translational study on looming-evoked defensive response and the underlying subcortical pathway in autism.rapidly approaching objects indicating threats can induce defensive response through activating a subcortical pathway comprising superior colliculus (sc), lateral posterior nucleus (lp), and basolateral amygdala (bla). abnormal defensive response has been reported in autism, and impaired synaptic connections could be the underlying mechanism. whether the sc-lp-bla pathway processes looming stimuli abnormally in autism is not clear. here, we found that looming-evoked defensive response is impaire ...201729116187
development and evaluation of a rt-qpcr assay for fast and sensitive rabies diagnosis.rabies virus is endemic to russia, among other countries. it is therefore critical to develop a high-quality and high-precision diagnostic procedure for the control and prevention of infection. the main objective of the research presented here was to develop a reliable rt-qpcr assay for rabies diagnostics. for this purpose, a rabv strains from various biological and geographical origins were used. in addition, rabies-positive and rabies-negative samples, as well as nucleic acids from other virus ...201829108902
terrestrial animal-derived rabies virus in a juvenile indian flying fox in sri lanka. 201729093322
regulation of nf-κb by the p105-abin2-tpl2 complex and relap43 during rabies virus infection.at the crossroad between the nf-κb and the mapk pathways, the ternary complex composed of p105, abin2 and tpl2 is essential for the host cell response to pathogens. the matrix protein (m) of field isolates of rabies virus was previously shown to disturb the signaling induced by relap43, a nf-κb protein close to rela/p65. here, we investigated how the m protein disturbs the nf-κb pathway in a relap43-dependant manner and the potential involvement of the ternary complex in this mechanism. using a ...201729084252
molecular characterization and phylogenetic relatedness of dog-derived rabies viruses circulating in cameroon between 2010 and 2016.rabies is enzootic among dog populations in some parts of cameroon and the risk of human rabies is thought to be steadily high in these regions. however, the molecular epidemiology of circulating rabies virus (rabv) has been hardly considered in cameroon as well as in most neighboring central african countries. to address this fundamental gap, 76 nucleoprotein (n) gene sequences of dog-derived rabv were obtained from 100 brain specimens sampled in cameroon from 2010 to 2016. studied sequences we ...201729084223
neuronal lrp4 regulates synapse formation in the developing cns.the low-density lipoprotein receptor-related protein 4 (lrp4) is essential in muscle fibers for the establishment of the neuromuscular junction. here, we show that lrp4 is also expressed by embryonic cortical and hippocampal neurons, and that downregulation of lrp4 in these neurons causes a reduction in density of synapses and number of primary dendrites. accordingly, overexpression of lrp4 in cultured neurons had the opposite effect inducing more but shorter primary dendrites with an increased ...201729061639
inhibition of rabies virus replication by interferon-stimulated gene 15 and its activating enzyme uba7.it was reported that isg15 and its activating enzyme uba7 have antiviral functions. however, there is no study to demonstrate whether isg15 and uba7 have anti-rabies virus function. in the current study, in vivo and in vitro anti-rabies virus function of isg15 and uba7 were investigated using rnai technology. the results showed that shrna knock-down of expression of isg15 and uba7 increased the titers of rabv in neuroblastoma cell line na and microglial cell line bv-2 cells and shrna knockdown o ...201729056542
evaluation of immune responses in dogs to oral rabies vaccine under field conditions.during the 20th century parenteral vaccination of dogs at central-point locations was the foundation of successful canine rabies elimination programs in numerous countries. however, countries that remain enzootic for canine rabies have lower infrastructural development compared to countries that have achieved elimination, which may make traditional vaccination methods less successful. alternative vaccination methods for dogs must be considered, such as oral rabies vaccine (orv). in 2016, a tradi ...201729054727
development and characterization of novel chimeric monoclonal antibodies for broad spectrum neutralization of rabies virus.current post-exposure prophylaxis for rabies virus infection has several limitations in terms of supply, cost, safety, and efficacy. attempts to replace human or equine rabies immune globulins (hrig or erig) have been made by several companies and institutes. we developed potent monoclonal antibodies to neutralize a broad spectrum of rabies viruses by screening hybridomas received from the u.s. centers for disease control and prevention (cdc). two kinds of chimeric human antibodies (chimeric #7 ...201729045436
efficacy of the oral rabies virus vaccine strain spbn gasgas in foxes and raccoon dogs.to test the immunogenicity and efficacy of a new oral rabies virus vaccine strain spbn gasgas in wildlife target species, one group of foxes and two groups of raccoon dogs were offered a bait containing 1.7 ml of the vaccine (106.6 ffu/ml; 106.8 ffu/dose) and subsequently challenged approximately 180 days later with a fox rabies virus isolate. one group of raccoon dogs (n=30) received the same challenge dose (100.7 micld50/ml) as the red foxes (n=29). the other group with raccoon dogs (n=28) tog ...201729042202
census and vaccination coverage of owned dog populations in four resource-limited rural communities, mpumalanga province, south africa.dogs (canis familiaris) are often free-roaming in sub-saharan african countries. rabies virus circulates in many of these populations and presents a public health issue. mass vaccination of dog populations is the recommended method to decrease the number of dog and human rabies cases. we describe and compare four populations of dogs and their vaccination coverage in four different villages (hluvukani, athol, utah and dixie) in bushbuckridge municipality, mpumalanga province, south africa. cross- ...201729041786
near-infrared fluorescent protein irfp720 is optimal for in vivo fluorescence imaging of rabies virus infection.in vivo imaging is a noninvasive method that enables real-time monitoring of viral infection dynamics in a small animal, which allows a better understanding of viral pathogenesis. in vivo bioluminescence imaging of virus infection is widely used but, despite its advantage over bioluminescence that no substrate administration is required, fluorescence imaging is not used because of severe autofluorescence. recently, several far-red and near-infrared (nir) fluorescent proteins (fps) have been deve ...201729039733
comparison of a novel human rabies monoclonal antibody to human rabies immunoglobulin for postexposure prophylaxis: a phase 2/3, randomized, single-blind, noninferiority, controlled study.lack of access to rabies immunoglobulin (rig) contributes to high rabies mortality. a recombinant human monoclonal antibody (sii rmab) was tested in a postexposure prophylaxis (pep) regimen in comparison with a human rig (hrig)-containing pep regimen.201829020321
rabies virus modifies host behaviour through a snake-toxin like region of its glycoprotein that inhibits neurotransmitter receptors in the cns.rabies virus induces drastic behaviour modifications in infected hosts. the mechanisms used to achieve these changes in the host are not known. the main finding of this study is that a region in the rabies virus glycoprotein, with homologies to snake toxins, has the ability to alter behaviour in animals through inhibition of nicotinic acetylcholine receptors present in the central nervous system. this finding provides a novel aspect to virus receptor interaction and host manipulation by pathogen ...201728993633
safety, efficacy and immunogenicity evaluation of the sag2 oral rabies vaccine in formosan ferret badgers.since 2013, rabies cases have been reported among formosan ferret badgers in taiwan, and they have been shown to be the major reservoirs for taiwanese enzootics. to control and eradicate rabies, the authorities plan to implement a vaccination programme. before distributing live vaccines in the field, this study assessed the safety, efficacy, and immunogenicity of sag2 vaccine on ferret badgers by direct oral instillation. after application of 109 tcid50/dose, no virus was excreted into the oral ...201728977009
recombinant newcastle disease virus rl-rvg enhances the apoptosis and inhibits the migration of a549 lung adenocarcinoma cells via regulating alpha 7 nicotinic acetylcholine receptors in vitro.the aim of this study were to investigate the possible pro-apoptotic mechanisms of the recombinant newcastle disease virus (ndv) strain rl-rvg, which expresses the rabies virus glycoprotein, in a549 lung adenocarcinoma cells via the regulation of alpha 7 nicotinic acetylcholine receptors (α7 nachrs) and to analyze the relationships between α7 nachr expression in lung cancer and the clinical pathological features.201728974241
direct conversion of human fibroblasts to functional excitatory cortical neurons integrating into human neural networks.human fibroblasts can be directly converted to several subtypes of neurons, but cortical projection neurons have not been generated.201728962665
3d reconstruction and standardization of the rat facial nucleus for precise mapping of vibrissal motor networks.the rodent facial nucleus (fn) comprises motoneurons (mns) that control the facial musculature. in the lateral part of the fn, populations of vibrissal motoneurons (vmns) innervate two groups of muscles that generate movements of the whiskers. vibrissal mns thus represent the terminal point of the neuronal networks that generate rhythmic whisking during exploratory behaviors and that modify whisker movements based on sensory-motor feedback during tactile-based perception. here, we combined retro ...201828958919
differentiated human sh-sy5y cells provide a reductionist model of herpes simplex virus 1 neurotropism.neuron-virus interactions that occur during herpes simplex virus (hsv) infection are not fully understood. neurons are the site of lifelong latency and are a crucial target for long-term suppressive therapy or viral clearance. a reproducible neuronal model of human origin would facilitate studies of hsv and other neurotropic viruses. current neuronal models in the herpesvirus field vary widely and have caveats, including incomplete differentiation, nonhuman origins, or the use of dividing cells ...201728956768
enhanced immune response to rabies viruses by the use of a liposome adjuvant in vaccines.essen regimen, the thai red cross two-site id regimen, zagreb schedule, and the eight-site id regimen are the standard rabies vaccines recommended by the world health organization (who). in this study, a liposomal rabies vaccine (liporv) was developed, which was found to facilitate the production of rabies virus neutralizing antibody (rvna) in balb/c mice. liposome solution was prepared with hydrogenated soya phosphatide and cholesterol. liporv composed of liposome solution and inactivated rabie ...201728953450
identification of two classes of somatosensory neurons that display resistance to retrograde infection by rabies virus.glycoprotein-deleted rabies virus-mediated monosynaptic tracing has become a standard method for neuronal circuit mapping, and is applied to virtually all parts of the rodent nervous system, including the spinal cord and primary sensory neurons. here we identified two classes of unmyelinated sensory neurons (nonpeptidergic and c-fiber low-threshold mechanoreceptor neurons) resistant to direct and trans-synaptic infection from the spinal cord with rabies viruses that carry glycoproteins in their ...201728951448
inhibition of mek-erk1/2-map kinase signalling pathway reduces rabies virus induced pathologies in mouse model.the extracellular signal-regulated kinase (erk) pathway has been shown to regulate pathogenesis of many viral infections, but its role during rabies virus (rv) infection in vivo is not clear. in the present study, we investigated the potential role of mek-erk1/2 signalling pathway in the pathogenesis of rabies in mouse model and its regulatory effects on pro-inflammatory cytokines and other mediators of immunity, and kinetics of immune cells. mice were infected with 25 ld50 of challenge virus st ...201728939254
oral vaccination of wildlife using a vaccinia-rabies-glycoprotein recombinant virus vaccine (raboral v-rg®): a global review.raboral v-rg® is an oral rabies vaccine bait that contains an attenuated ("modified-live") recombinant vaccinia virus vector vaccine expressing the rabies virus glycoprotein gene (v-rg). approximately 250 million doses have been distributed globally since 1987 without any reports of adverse reactions in wildlife or domestic animals since the first licensed recombinant oral rabies vaccine (orv) was released into the environment to immunize wildlife populations against rabies. v-rg is genetically ...201728938920
development of molecular confirmation tools for swift and easy rabies diagnostics.as rabies still represents a major public threat with tens of thousands of deaths per year, particularly in developing countries, adequate surveillance based on rapid and reliable rabies diagnosis for both humans and animals is essential. rabies diagnosis relies on highly sensitive and specific laboratory tests for detection of viral antigens. among those tests, at present the immunofluorescence antibody test is the "gold standard test" for rabies diagnosis, followed by virus isolation in either ...201728938887
single visit rabies pre-exposure priming induces a robust anamnestic antibody response after simulated post-exposure vaccination: results of a dose-finding study.the current standard 3-dose intramuscular rabies prep schedule suffers from a number of disadvantages that severely limit accessibility and availability. the cost of is often prohibitive, it requires 3 visits to the clinic, and there are regular vaccine shortages.201728931127
phosphoprotein gene contributes to the enhanced apoptosis induced by wild-type rabies virus gd-sh-01 in vitro.previous research demonstrated that the matrix protein (m) and glycoprotein (g) of attenuated rabies virus (rabv) strains are involved in the induction of host cell apoptosis. in this work, we show that wild-type (wt) rabv gd-sh-01 induces significantly greater apoptosis than the attenuated strain hep-flury. in order to identify the gene(s) accounting for this phenotype, five recombinant rabvs (rrabvs) were constructed by replacing each single gene of hep-flury with the corresponding gene of gd- ...201728928726
production of recombinant rabies virus glycoprotein by insect cells in a single-use fixed-bed bioreactor.a single-use fixed-bed bioreactor (icellis nano) can be used for cultivating non adherent insect cells, which can be then recovered for scaling up or for harvesting a membrane-associated viral glycoprotein with high quality in terms of preserved protein structure and biological function. here, we describe the procedures for establishing genetically modified drosophila melanogaster schneider 2 (s2) cell cultures in the icellis nano bioreactor and for quantifying by elisa the recombinant rabies vi ...201828921430
changes in innervation of lumbar motoneurons and organization of premotor network following training of transected adult rats.rats with complete spinal cord transection (sct) can recover hindlimb locomotor function under strategies combining exercise training and 5-ht agonist treatment. this recovery is expected to result from structural and functional re-organization within the spinal cord below the lesion. to begin to understand the nature of this reorganization, we examined synaptic changes to identified gastrocnemius (gs) or tibialis anterior (ta) motoneurons (mns) in sct rats after a schedule of early exercise tra ...201828917641
re-emergence of rabies virus maintained by canid populations in paraguay.paraguay has registered no human cases of rabies since 2004, and the last case in dogs, reported in 2009, was due to a variant maintained in the common vampire bat "desmodus rotundus". in 2014, a dog was diagnosed as positive for rabies with aggression towards a boy and all required measures of control were successfully adopted. epidemiological investigation revealed that the dog was not vaccinated and had been attacked by a crab-eating fox, "zorro" (cerdocyon thous). the sample was diagnosed by ...201828913904
rabies screen reveals gpe control of cocaine-triggered plasticity.identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. cocaine increased rabies-labelled inputs from the ...201728902833
a novel approach to a rabies vaccine based on a recombinant single-cycle flavivirus vector.the replivax® vaccine (rv) platform is based on flavivirus genomes that are rationally attenuated by deletion. these single-cycle rv vaccine candidates targeting flavivirus pathogens have been demonstrated to be safe, highly immunogenic, and efficacious in animal models, including non-human primates. here we show utility of the technology for delivery of a non-flavivirus immunogen by engineering several west nile-based rv vectors to express full-length rabies virus g protein. the rabies virus g ...201728899628
immunogenicity of orfv-based vectors expressing the rabies virus glycoprotein in livestock species.the parapoxvirus orf virus (orfv) encodes several immunomodulatory proteins (imps) that modulate host-innate and pro-inflammatory responses and has been proposed as a vaccine delivery vector for use in animal species. here we describe the construction and characterization of two recombinant orfv vectors expressing the rabies virus (rabv) glycoprotein (g). the rabv-g gene was inserted in the orfv024 or orfv121 gene loci, which encode for imps that are unique to parapoxviruses and inhibit activati ...201728898730
a self-killing rabies virus that leaves a trace on the dna.although modified rabies viruses have emerged as a powerful tool for tracing the inputs to genetically defined populations of neurons, the toxicity of the virus has limited its utility. a recent study employed a self-inactivating rabies (sir) virus that enables recording or manipulation of targeted neurons for months.201728890212
generation of a novel live rabies vaccine strain with a high level of safety by introducing attenuating mutations in the nucleoprotein and glycoprotein.the current live rabies vaccine sag2 is attenuated by only one mutation (arg-to-glu) at position 333 in the glycoprotein (g333). this fact generates a potential risk of the emergence of a pathogenic revertant by a back mutation at this position during viral propagation in the body. to circumvent this risk, it is desirable to generate a live vaccine strain highly and stably attenuated by multiple mutations. however, the information on attenuating mutations other than that at g333 is very limited. ...201728882441
vaccines against botulism.botulinum neurotoxins (bont) cause the flaccid paralysis of botulism by inhibiting the release of acetylcholine from motor neurons. there are seven serotypes of bont (a-g), with limited therapies, and no fda approved vaccine for botulism. an investigational formalin-inactivated penta-serotype-bont/a-e toxoid vaccine was used to vaccinate people who are at high risk of contracting botulism. however, this formalin-inactivated penta-serotype-bont/a-e toxoid vaccine was losing potency and was discon ...201728869493
a data platform to improve rabies prevention, sri lanka.in sri lanka, rabies prevention initiatives are hindered by fragmented and delayed information-sharing that limits clinicians' ability to follow patients and impedes public health surveillance.201728867845
recombinant rabies virus expressing il-15 enhances immunogenicity through promoting the activation of dendritic cells in mice.rabies remains a public health threat that kills approximately 59,000 people worldwide each year, most of which are from the developing countries of africa and asia where dog rabies are endemic. therefore, developing an affordable and efficacious vaccine is crucial for rabies control in these countries. interleukin (il)-15, an immunoregulatory cytokine, is a pluripotent molecule with therapeutic potential, which targets many cell types and links the innate and adaptive immune system. in this stu ...201728861771
glycoprotein-g-gene-based molecular and phylogenetic analysis of rabies viruses associated with a large outbreak of bovine rabies in southern brazil.a large outbreak of hematophagous-bat-associated bovine rabies has been occurring in rio grande do sul (rs), the southernmost brazilian state, since 2011, with official estimates exceeding 50,000 cattle deaths. the present article describes a genetic characterization of rabies virus (rabv) recovered from 59 affected cattle and two sheep, from 56 herds in 16 municipalities (2012-2016). molecular analysis was performed using the nucleotide (nt) and predicted amino acid (aa) sequences of rabv glyco ...201728856449
incidence of human rabies and characterization of rabies virus nucleoprotein gene in dogs in fujian province, southeast china, 2002-2012.rabies is a global fatal infectious viral disease that is characterized by a high mortality after onset of clinical symptoms. recently, there has been an increase in the incidence of rabies in china. the aim of this study was to investigate the incidence of human rabies and characterize the rabies virus nucleoprotein gene in dogs sampled from fujian province, southeast china from 2002 to 2012.201728854892
plant-made vaccines and reagents for the one health initiative.the one health initiative is increasingly becoming a prominent discussion topic in animal and human health, with its focus on prevention of spread of zoonotic diseases, both in animals, and from animals to humans. an important part of one health is that diagnostics and vaccines for diseases may be the same thing - and be used for both humans and animals. one potential problem standing in the way of wider adoption of one health principles, though, is that use of conventional cell fermentation sys ...201728846485
comparison of a micro-neutralization test with the rapid fluorescent focus inhibition test for measuring rabies virus neutralizing antibodies.the rapid fluorescent focus inhibition test (rffit) is routinely used in the united states to measure rabies virus neutralizing antibodies (rvna). rffit has a long history of reproducible and reliable results. the test has been modified over the years to use smaller volumes of reagents and samples, but requires a 50 μl minimum volume of test serum. to conduct pathogenesis studies, small laboratory animals such as mice are regularly tested for rvna, but the minimum volume for a standard rffit may ...201728845465
rabies virus transmission in solid organ transplantation, china, 2015-2016.we report rabies virus transmission among solid organ transplantation recipients in changsha, china, in 2016. two recipients were confirmed to have rabies and died. our findings suggest that more attention should be paid to the possibility of rabies virus transmission through organ transplantation for clinical and public health reasons.201728820377
molecular characterization of atypical antigenic variants of canine rabies virus reveals its reintroduction by wildlife vectors in southeastern mexico.rabies is an infectious viral disease that is practically always fatal following the onset of clinical signs. in mexico, the last case of human rabies transmitted by dogs was reported in 2006 and canine rabies has declined significantly due to vaccination campaigns implemented in the country. here we report on the molecular characterization of six rabies virus strains found in yucatan and chiapas, remarkably, four of them showed an atypical reaction pattern when antigenic characterization with a ...201728819692
codon usage bias in the n gene of rabies virus.since its emergence, rabies virus (rabv) has been a major worldwide concern especially in developing countries. the nucleoprotein (n) of rabv is highly conserved and key for genetic typing, thus a better understanding of the n gene evolutionary trajectory can assist the development of control measures. we found that the n gene of rabv has a low codon usage bias with a mean effective number of codons (enc) value of 56.33 influenced by both mutation pressure and natural selection. however, neutral ...201728818621
enhancing immune responses to cancer vaccines using multi-site injections.for a vaccine to be effective it must induce a sufficiently robust and specific immune response. multi-site injection protocols can increase the titers of rabies virus-neutralizing antibodies. hypothetically, spreading a vaccine dose across multiple lymphatic drainage regions could also potentiate t cell responses. we used a replication-deficient adenovirus serotype 5-vectored cancer vaccine targeting the melanoma-associated antigen dopachrome tautomerase. clinically, high numbers of tumor-infil ...201728814733
a time-resolved fluoroimmunoassay to assay the rabies virus glycoprotein: application for estimation of human rabies vaccine potency.replacement of the in vivo rabies vaccine potency test (nih test) by in vitro methods had been discussed by several researcher including who expert working groups. in this paper, a time-resolved fluoroimmunoassay (trfia) for the assay of rabies virus glycoprotein in rabies vaccine was first established to estimate the rabies vaccine potency by using specific monoclonal antibody that only recognized the native, trimeric and immunogenic form of rabies virus glycoprotein. potency of the rabies viru ...201728779162
a genetically modified rabies vaccine (erags) induces protective immunity in dogs and cattle.the current live attenuated rabies vaccine must be replaced with a safer vaccine based on the erags strain to prevent rabies in south korea. we evaluated the safety and immunogenicity of a new strain in dogs and cattle.201728775977
molecular function analysis of rabies virus rna polymerase l protein by using an l gene-deficient virus.while the rna-dependent rna polymerase l protein of rabies virus (rabv), a member of the genus lyssavirus of the family rhabdoviridae, has potential to be a therapeutic target for rabies, the molecular functions of this protein have remained largely unknown. in this study, to obtain a novel experimental tool for molecular function analysis of the rabv l protein, we established by using a reverse genetics approach an l gene-deficient rabv (nishi-δl/nluc), which infects, propagates, and correspond ...201728768857
hippocampal tert regulates spatial memory formation through modulation of neural development.the molecular mechanism of memory formation remains a mystery. here, we show that tert, the catalytic subunit of telomerase, gene knockout (tert-/-) causes extremely poor ability in spatial memory formation. knockdown of tert in the dentate gyrus of adult hippocampus impairs spatial memory processes, while overexpression facilitates it. we find that tert plays a critical role in neural development including dendritic development and neuritogenesis of hippocampal newborn neurons. a monosynaptic p ...201728757168
safety and immunogenicity of a mrna rabies vaccine in healthy adults: an open-label, non-randomised, prospective, first-in-human phase 1 clinical trial.vaccines based on mrna coding for antigens have been shown to be safe and immunogenic in preclinical models. we aimed to report results of the first-in-human proof-of-concept clinical trial in healthy adults of a prophylactic mrna-based vaccine encoding rabies virus glycoprotein (cv7201).201728754494
immunological aspects of rabies: a literature review.rabies is a lethal disease caused by the neurotropic virus rabies virus (rabv), and it remains an important public health problem globally. it is known that the host immune response is important for control of viral infection and promoting viral clearance. in this context, it is well documented that, in addition to rabv neutralizing antibody, interferons and cell-mediated immunity also have an important role in preventing the establishment of disease. on the other hand, rabv suppresses host immu ...201728726129
[c-terminal lysosome targeting domain of cd63 modifies cellular localization of rabies virus glycoprotein].the glycoprotein of rabies virus is the central antigen elicited the immune response to infection; therefore, the majority of developing anti-rabies vaccines are based on this protein. in order to increase the efficacy of dna immunogen encoding rabies virus glycoprotein, the construction of chimeric protein with the cd63 domain has been proposed. the cd63 is a transmembrane protein localized on the cell surface and in lysosomes. the lysosome targeting motif gyevm is located at its c-terminus. we ...201728707662
increased transgene expression level of rabies virus vector for transsynaptic tracing.viral vectors that can infect neurons transsynaptically and can strongly express foreign genes are useful for investigating the organization of neural circuits. we previously developed a propagation-competent rabies virus (rv) vector based on a highly attenuated hep-flury strain (rhep5.0-cvsg), which selectively infects neurons and propagates between synaptically connected neurons in a retrograde direction. its relatively low level of transgene expression, however, makes immunostaining necessary ...201728700657
life-long genetic and functional access to neural circuits using self-inactivating rabies virus.neural networks are emerging as the fundamental computational unit of the brain and it is becoming progressively clearer that network dysfunction is at the core of a number of psychiatric and neurodegenerative disorders. yet, our ability to target specific networks for functional or genetic manipulations remains limited. monosynaptically restricted rabies virus facilitates the anatomical investigation of neural circuits. however, the inherent cytotoxicity of the rabies largely prevents its imple ...201728689641
a single center, open label study of intradermal administration of an inactivated purified chick embryo cell culture rabies virus vaccine in adults.in the usa, rabies vaccines (rvs) are licensed for intramuscular (im) use only, although rvs are licensed for use by the intradermal (id) route in many other countries. recent limitations in supplies of rv in the usa reopened discussions on the more efficient use of available biologics, including utilization of more stringent risk assessments, and potential id rv administration. a clinical trial was designed to compare the immunogenic and adverse effects of a purified chicken embryo cell (pcec) ...201728688782
first complete genomic sequence of a rabies virus from the republic of tajikistan obtained directly from a flinders technology associates card.a brain homogenate derived from a rabid dog in the district of tojikobod, republic of tajikistan, was applied to a flinders technology associates (fta) card. a full-genome sequence of rabies virus (rabv) was generated from the fta card directly without extraction, demonstrating the utility of these cards for readily obtaining genetic data.201728684566
lyssavirus phosphoproteins increase mitochondrial complex i activity and levels of reactive oxygen species.we have previously demonstrated that serine residues at positions 162 and 166 of the rabies virus (rabv) phosphoprotein (p) are critical for oxidative stress induced by cvs in cultured cells. we have now evaluated the p of two street rabv variants and mokola (mok) virus. the p of these viruses, like cvs, induces an increase in complex i activities and reactive oxygen species levels in transfected cells. although the sequence homology of p is only 45% with mok (higher for street viruses) and cvs, ...201728681345
negri bodies are viral factories with properties of liquid organelles.replication of mononegavirales occurs in viral factories which form inclusions in the host-cell cytoplasm. for rabies virus, those inclusions are called negri bodies (nbs). we report that nbs have characteristics similar to those of liquid organelles: they are spherical, they fuse to form larger structures, and they disappear upon hypotonic shock. their liquid phase is confirmed by frap experiments. live-cell imaging indicates that viral nucleocapsids are ejected from nbs and transported along m ...201728680096
striatal cholinergic interneurons and parkinson's disease.giant, aspiny cholinergic interneurons (chis) have long been known to be key nodes in the striatal circuitry controlling goal-directed actions and habits. in recent years, new experimental approaches, like optogenetics and monosynaptic rabies virus mapping, have expanded our understanding of how chis contribute to the striatal activity underlying action selection and the interplay of dopaminergic and cholinergic signaling. these approaches also have begun to reveal how chi function is distorted ...201728677242
defect of rabies virus phosphoprotein in its interferon-antagonist activity negatively affects viral replication in muscle cells.attenuated derivative rabies virus ni-ce replicates in muscle cells less efficiently than does the parental pathogenic strain nishigahara. to examine the mechanism underlying the less efficient replication of ni-ce, we compared the activities of ni-ce and nishigahara phosphoproteins, viral interferon (ifn) antagonists, to suppress ifn-β promoter activity in muscle cells and we demonstrated a defect of ni-ce phosphoprotein in this ability. treatment with an ifn-β-neutralizing antibody improved th ...201728674326
multivariate analysis of the immune response to a vaccine as an alternative to the repetition of animal challenge studies for vaccines with demonstrated efficacy.the assessment of vaccine combinations, or the evaluation of the impact of minor modifications of one component in well-established vaccines, requires animal challenges in the absence of previously validated correlates of protection. as an alternative, we propose conducting a multivariate analysis of the specific immune response to the vaccine. this approach is consistent with the principles of the 3rs (refinement, reduction and replacement) and avoids repeating efficacy studies based on infecti ...201728669388
monosynaptic retrograde tracing of neurons expressing the g-protein coupled receptor gpr151 in the mouse brain.gpr151 is a g-protein coupled receptor for which the endogenous ligand remains unknown. in the nervous system of vertebrates, its expression is enriched in specific diencephalic structures, where the highest levels are observed in the habenular area. the habenula has been implicated in a range of different functions including behavioral flexibility, decision making, inhibitory control, and pain processing, which makes it a promising target for treating psychiatric and neurological disease. this ...201728657115
comparison of the protective efficacy between single and combination of recombinant adenoviruses expressing complete and truncated glycoprotein, and nucleoprotein of the pathogenic street rabies virus in mice.rabies is an important viral zoonosis that causes acute encephalitis and death in mammals. to date, several recombinant vaccines have been developed based on g protein, which is considered to be the main antigen, and these vaccines are used for rabies control in many countries. most recombinant viruses expressing rabv g protein retain the g gene from attenuated rabv. not enough is currently known about the protective effect against rabv of a combination of recombinant adenoviruses expressing the ...201728646885
asn194lys mutation in rvg29 peptide increases gfp transgene delivery by endocytosis to neuroblastoma and astrocyte cells.a cell-penetrating peptide-based delivery system could target specific types of cells for therapeutic genes delivery. to increase the gene delivery efficiency into neuronal phenotype cells, we introduced an asn194lys mutation to rvg29 peptide derived from rabies virus glycoprotein and added a nuclear localization signal to enhance its nuclear import.201728643952
ifit2 is a restriction factor in rabies virus pathogenicity.understanding the interactions between rabies virus (rabv) and individual host cell proteins is critical for the development of targeted therapies. here we report that interferon-induced protein with tetratricopeptide repeats 2 (ifit2), an interferon-stimulated gene (isg) with possible rna-binding capacity, is an important restriction factor for rabies virus. when ifit2 was depleted, rabv grew more quickly in mouse neuroblastoma cells in vitro this effect was replicated in vivo, where ifit2 knoc ...201728637751
rabies virus co-localizes with early (rab5) and late (rab7) endosomal proteins in neuronal and sh-sy5y cells.rabies virus (rabv) is a highly neurotropic virus that follows clathrin-mediated endocytosis and ph-dependent pathway for trafficking and invasion into endothelial cells. early (rab5, eea1) and late (rab7, lamp1) endosomal proteins play critical roles in endosomal sorting, maturity and targeting various molecular cargoes, but their precise functions in the early stage of rabv neuronal infection remain elusive. in this study, the relationship between enigmatic entry of rabv with these endosomal p ...201728634871
exosome mediated delivery of mir-124 promotes neurogenesis after ischemia.the intrinsic ability of neurogenesis after stroke has been proven weak, which results in insufficient repair of injury in the nerve system. recent studies suggest multiple micrornas (mirnas) are involved in the neuroremodeling process. targeted mirnas delivery for amplification of neurogenesis is promising in promoting the prognosis after ischemia. here, we showed that modified exosomes, with rabies virus glycoprotein (rvg) fused to exosomal protein lysosome-associated membrane glycoprotein 2b ...201728624203
april:taci axis is dispensable for the immune response to rabies vaccination.there is significant need to develop a single-dose rabies vaccine to replace the current multi-dose rabies vaccine regimen and eliminate the requirement for rabies immune globulin in post-exposure settings. to accomplish this goal, rabies virus (rabv)-based vaccines must rapidly activate b cells to secrete antibodies which neutralize pathogenic rabv before it enters the cns. increased understanding of how b cells effectively respond to rabv-based vaccines may improve efforts to simplify post-exp ...201728619678
rational design of rabies vaccine formulation for enhanced stability.vaccines are often lyophilized in order to retain their stability and efficacy for a longer period of time. however, the same lyophilization process may also cause a major degradation of the vaccine, especially during early phases of manufacturing, leading to a loss of potency of the product. many viral diseases, such as rabies, are acute and fatal unless the vaccine is administered prior to exposure or the onset of symptoms in the case of postexposure treatment.201728618756
investigation of rabies virus glycoprotein carboxyl terminus as an in vitro predictive tool of neurovirulence. a 3r approach.in the field of live viral vaccines production, there is an unmet need for in vitro tests complying a 3r approach (refine, replace and reduce the use of animal experimentation) to replace the post-licensing safety tests currently assayed in animals. here, we performed a pilot study evaluating whether virulence of rabies virus, rabv, can be forecast by an in vitro test of neurite outgrowth. the rationale to use neurite outgrowth as a read-out for this test is based on the salient property of the ...201728602914
nicotinic acetylcholine receptor alpha 1(nachrα1) subunit peptides as potential antiviral agents against rabies virus.rabies virus (rabv) is neurotropic and infects all warm-blooded animals. the binding of the virus with host cell receptor components is critical for infection. the present study reports the interaction of nicotinic acetylcholine receptor alpha 1 (nachrα1) peptides with the rabies virus glycoprotein (rabvg) to design potential anti-rabies agents. the nachrα1peptide sequences from different species (bovine, human and electric fish/torpedo) were synthesized and their secondary structures were chara ...201728587964
cross-border spread, lineage displacement and evolutionary rate estimation of rabies virus in yunnan province, china.rabies is an important but underestimated threat to public health, with most cases reported in asia. since 2000, a new epidemic wave of rabies has emerged in yunnan province, southwestern china, which borders three countries in southeast asia.201728578663
a facile way of modifying layered double hydroxide nanoparticles with targeting ligand-conjugated albumin for enhanced delivery to brain tumour cells.active targeting of nanoparticles (nps) for cancer treatment has attracted increasing interest in the past decades. various ligand modification strategies have been used to enhance the targeting of nps to the tumor site. however, how to reproducibly fabricate diverse targeting nps with narrowly changeable biophysiochemical properties remains as a major challenge. in this study, layered double hydroxide (ldh) nps were modified as a target delivery system. two brain tumor targeting ligands, i.e., ...201728574700
investigating the effect of carbon source on rabies virus glycoprotein production in pichia pastoris by a transcriptomic approach.several factors affect protein expression in pichia pastoris, one among them is the carbon source. in this work, we studied the effect of this factor on the expression level of rabies virus glycoprotein (rabv-g) in two recombinant clones harboring seven copies of the gene of interest. the expression was driven either by the constitutive glyceraldehyde-3-phosphate dehydrogenase (gap) promoter or the inducible alcohol oxidase1 (aox1) promoter. clones were compared in terms of cell physiology and c ...201728523730
sero-prevalence of virus neutralizing antibodies for rabies in different groups of dogs following vaccination.mass vaccination of dogs is considered fundamental for national rabies control programmes in sri lanka, as dog is the main reservoir and transmitter of the disease.201728521804
targeting the central nervous system (cns): a review of rabies virus-targeting strategies.the transport of drugs across the blood-brain barrier is challenging. the use of peptide sequences derived from viruses with a central nervous system (cns) tropism is one elegant option. a prominent example is the rabies virus glycopeptide-29 (rvg-29), which is said to enable a targeted brain delivery. although the entry mechanism of the rabies virus into the cns is very well characterized, it is unknown whether rvg-29-functionalized drug delivery systems (ddss) follow this pathway. rvg-29-funct ...201728514853
rapid reverse genetics systems for rhabdoviruses: from forward to reverse and back again.methods to recover recombinant negative strand rna viruses (rnsvs) from cloned cdnas have been significantly improved in more than two decades of nsv reverse genetics . in particular, for non-segmented negative strand rna viruses (nnsvs ) like rhabdoviruses , time-consuming generation of reverse genetics systems by stitching pcr subfragments of genomic rhabdovirus cdnas using ligase-based conventional cloning approaches limited the number of available recombinant virus cdna clones. as genetic va ...201728508221
susceptibility of neuroblastoma cells to rabies virus may be affected by passage number.maintaining a healthy, continuous immortalized cell line is essential for rabies laboratories that perform virus isolation assays and test for the presence of viral neutralizing antibodies. individuals who routinely work with rabies virus, such as rabies laboratory employees, or those who may have a high potential for exposure to rabies virus, including veterinarians, should be tested for the presence of anti-rabies viral neutralizing antibodies (vna) every 6-24 months, depending on potential ex ...201728506631
rabies virus infection induces microtubule depolymerization to facilitate viral rna synthesis by upregulating hdac6.rabies virus (rabv) is the cause of rabies, and is associated with severe neurological symptoms, high mortality rate, and a serious threat to human health. although cellular tubulin has recently been identified to be incorporated into rabv particles, the effects of rabv infection on the microtubule cytoskeleton remain poorly understood. in this study, we show that rabv infection induces microtubule depolymerization as observed by confocal microscopy, which is closely associated with the formatio ...201728491824
comprehensive monosynaptic rabies virus mapping of host connectivity with neural progenitor grafts after spinal cord injury.neural progenitor cells grafted to sites of spinal cord injury have supported electrophysiological and functional recovery in several studies. mechanisms associated with graft-related improvements in outcome appear dependent on functional synaptic integration of graft and host systems, although the extent and diversity of synaptic integration of grafts with hosts are unknown. using transgenic mouse spinal neural progenitor cell grafts expressing the tva and g-protein components of the modified r ...201728479302
emission transformation in cdse/zns quantum dots conjugated to biomolecules.the variation of photoluminescence (pl) spectra in cdse/zns quantum dots (qds) at the conjugation to antibodies (abs) has been investigated and discussed in this paper. two types of cdse/zns qds with different cdse core sizes (5.4 and 6.4nm) and emissions (605 and 655nm) were studied before and after the conjugation to anti-interleukin-10 (il-10) and anti-pseudo rabies virus (prv) abs. the pl high energy shift and asymmetric shape of pl bands have been detected in bioconjugated qds. note that th ...201728477576
organization of dopamine and serotonin system: anatomical and functional mapping of monosynaptic inputs using rabies virus.dopamine and serotonin play critical roles in flexible behaviors and are related to various psychiatric and motor disorders. this paper reviews the global organization of dopamine and serotonin systems through recent findings using a modified rabies virus. we first introduce methods for comprehensive mapping of monosynaptic inputs. we then describe quantitative comparisons across the data regarding monosynaptic inputs to dopamine neurons versus serotonin neurons. there is surprising similarity b ...201728476484
rabies tracing of birthdated dentate granule cells in rat temporal lobe epilepsy.to understand how monosynaptic inputs onto adult-born dentate granule cells (dgcs) are altered in experimental mesial temporal lobe epilepsy (mtle) and whether their integration differs from early-born dgcs that are mature at the time of epileptogenesis.201728470680
type 1 immune mechanisms driven by the response to infection with attenuated rabies virus result in changes in the immune bias of the tumor microenvironment and necrosis of mouse gl261 brain tumors.immunotherapeutic strategies for malignant glioma have to overcome the immunomodulatory activities of m2 monocytes that appear in the circulation and as tumor-associated macrophages (tams). m2 cell products contribute to the growth-promoting attributes of the tumor microenvironment (tme) and bias immunity toward type 2, away from the type 1 mechanisms with antitumor properties. to drive type 1 immunity in cns tissues, we infected gl261 tumor-bearing mice with attenuated rabies virus (rabv). thes ...201728461570
rescue of a wild-type rabies virus from cloned cdna and assessment of the proliferative capacity of recombinant viruses.reverse genetic systems (rgs) have been widely used for fixed rabies virus (rabv) strains. however, rgs, for wild-type (wt) strains, have been seldom reported despite the value of this approach in defining the biological characteristics of these strains. in this work, we developed a wt rgs using a swine-origin rabv strain (gd-sh-01) for the first time. in order to have a better understanding of the contribution and function of individual gene on viral proliferation for wt rabv isolates, we const ...201728447192
roles of multiple globus pallidus territories of monkeys and humans in motivation, cognition and action: an anatomical, physiological and pathophysiological review.the globus pallidus (gp) communicates with widespread cortical areas that support various functions, including motivation, cognition and action. anatomical tract-tracing studies revealed that the anteroventral gp communicates with the medial prefrontal and orbitofrontal cortices, which are involved in motivational control; the anterodorsal gp communicates with the lateral prefrontal cortex, which is involved in cognitive control; and the posterior gp communicates with the frontal motor cortex, w ...201728442999
pathological lesions in the central nervous system and peripheral tissues of ddy mice with street rabies virus (1088 strain).most studies on rabies virus pathogenesis in animal models have employed fixed rabies viruses, and the results of those employing street rabies viruses have been inconsistent. therefore, to clarify the pathogenesis of street rabies virus (1088 strain) in mice, 106 focus forming units were inoculated into the right hindlimb of ddy mice (6 weeks, female). at 3 days postinoculation (dpi), mild inflammation was observed in the hindlimb muscle. at 5 dpi, ganglion cells in the right lumbosacral spinal ...201728428485
community-based survey during rabies outbreaks in rangjung town, trashigang, eastern bhutan, 2016.rabies is a highly fatal disease transmitted through the bite of a rabid animal. human deaths can be prevented by prompt administering of rabies vaccine and rabies immunoglobulin following the exposure. an assessment of community knowledge, awareness and practices on rabies is important during outbreak to understand their preparedness and target educational messages and response activities by the rapid response team.201728415972
targeted drug delivery system to neural cells utilizes the nicotinic acetylcholine receptor.drug delivery to the brain is still a major challenge in the field of therapeutics, especially for large and hydrophilic compounds. in order to achieve drug delivery of therapeutic concentration in the central nervous system, the problematic blood brain barrier (bbb) must be overcome. this work presents the formulation of a targeted nanoparticle-based drug delivery system using a specific neural cell targeting ligand, rabies virus derived peptide (rdp). characterization studies revealed that rdp ...201728412449
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