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rescue of a wild-type rabies virus from cloned cdna and assessment of the proliferative capacity of recombinant viruses.reverse genetic systems (rgs) have been widely used for fixed rabies virus (rabv) strains. however, rgs, for wild-type (wt) strains, have been seldom reported despite the value of this approach in defining the biological characteristics of these strains. in this work, we developed a wt rgs using a swine-origin rabv strain (gd-sh-01) for the first time. in order to have a better understanding of the contribution and function of individual gene on viral proliferation for wt rabv isolates, we const ...201728447192
roles of multiple globus pallidus territories of monkeys and humans in motivation, cognition and action: an anatomical, physiological and pathophysiological review.the globus pallidus (gp) communicates with widespread cortical areas that support various functions, including motivation, cognition and action. anatomical tract-tracing studies revealed that the anteroventral gp communicates with the medial prefrontal and orbitofrontal cortices, which are involved in motivational control; the anterodorsal gp communicates with the lateral prefrontal cortex, which is involved in cognitive control; and the posterior gp communicates with the frontal motor cortex, w ...201728442999
pathological lesions in the central nervous system and peripheral tissues of ddy mice with street rabies virus (1088 strain).most studies on rabies virus pathogenesis in animal models have employed fixed rabies viruses, and the results of those employing street rabies viruses have been inconsistent. therefore, to clarify the pathogenesis of street rabies virus (1088 strain) in mice, 106 focus forming units were inoculated into the right hindlimb of ddy mice (6 weeks, female). at 3 days postinoculation (dpi), mild inflammation was observed in the hindlimb muscle. at 5 dpi, ganglion cells in the right lumbosacral spinal ...201728428485
community-based survey during rabies outbreaks in rangjung town, trashigang, eastern bhutan, 2016.rabies is a highly fatal disease transmitted through the bite of a rabid animal. human deaths can be prevented by prompt administering of rabies vaccine and rabies immunoglobulin following the exposure. an assessment of community knowledge, awareness and practices on rabies is important during outbreak to understand their preparedness and target educational messages and response activities by the rapid response team.201728415972
targeted drug delivery system to neural cells utilizes the nicotinic acetylcholine receptor.drug delivery to the brain is still a major challenge in the field of therapeutics, especially for large and hydrophilic compounds. in order to achieve drug delivery of therapeutic concentration in the central nervous system, the problematic blood brain barrier (bbb) must be overcome. this work presents the formulation of a targeted nanoparticle-based drug delivery system using a specific neural cell targeting ligand, rabies virus derived peptide (rdp). characterization studies revealed that rdp ...201728412449
rabies acquired through kidney transplantation in a child: a case report.rabies is usually transmitted to humans through bites of infected animals; however, it can rarely be transmitted through deceased donor organs or tissues when not suspected. here, we report a case of rabies transmission in a child. the child was a 5-year-old girl who was admitted to the pediatric intensive care unit with encephalitis of unexplained cause 3.5 months after she received a kidney transplant from a deceased donor. the laboratory and imaging studies did not reveal any explanation for ...201728411355
comparison of the immunogenicity and safety of the purified chick embryo cell rabies vaccine manufactured in india and germany: a randomized, single blind, multicentre, phase iv clinical study.this phase iv, single blind study assessed the immunogenicity and safety of india-manufactured purified chick embryo cell rabies vaccine (pcecv), compared with a german-manufactured batch obtained by the same production process. a total of 340 participants enrolled at 2 study sites in india were randomized (1:1:1:1) in 4 groups to receive a 5-dose essen regimen with either 1 of the 3 indian batches (pcecv-i) or the german batch (pcecv-g), administered on days (d) 0, 3, 7, 14 and 30. the lot-to-l ...201728406752
pathobiological investigation of naturally infected canine rabies cases from sri lanka.the recommended screening of rabies in 'suspect' animal cases involves testing fresh brain tissue. the preservation of fresh tissue however can be difficult under field conditions and formalin fixation provides a simple alternative that may allow a confirmatory diagnosis. the occurrence and location of histopathological changes and immunohistochemical (ihc) labelling for rabies in formalin fixed paraffin embedded (ffpe) canine brain is described in samples from 57 rabies suspect cases from sri-l ...201728403882
sequencing and sequence analysis of partial nucleoprotein (n) gene and phylogenetic analysis of rabies virus field isolates from gujarat state, india.the present study was undertaken with an aim of characterization of rabies virus (genus lyssavirus of the family rhabdoviridae under the order mononegavirales) by sequencing of partial nucleoprotein (n) gene of rabies virus and phylogenetic analysis to know the genotype and lineage of rabies virus present in gujarat state of india. a total of 32 samples (18 brain samples and 14 saliva samples) were aseptically collected from live and dead animals (viz. dog, buffalo, cow, goat, donkey and hyena) ...201729291220
the path towards effective antivirals against rabies.rabies virus remains an important burden of disease claiming an estimated 60,000 lives each year, mainly children, and having a huge economical and societal cost. post-exposure prophylaxis (pep) is highly effective, however in patients that present with neurological symptoms the case-fatality ratio is extremely high (>99%). during the last decades several attempts to identify potent and effective antivirals were made. only a few of these demonstrated improvement in clinical signs in animal studi ...201729279280
mannitol treatment is not effective in therapy of rabies virus infection in mice.rabies is a deadly viral disease with an extremely high fatality rate in humans. previously, it was suggested that an enhancement of the blood-brain barrier (bbb) permeability, which allows immune cells and/or antibodies to enter the central nervous system (cns) tissue, is critical to clear the infection. in this study, we utilised mannitol to increase bbb permeability in mice infected with highly pathogenic silver-haired bat rabies virus (shbrv). we found that intraperitoneal injection of manni ...201729274698
landscape attributes governing local transmission of an endemic zoonosis: rabies virus in domestic dogs.landscape heterogeneity plays an important role in disease spread and persistence but quantifying landscape influences and their scale-dependence is challenging. studies have focused on how environmental features or global transport networks influence pathogen invasion and spread, but their influence on local transmission dynamics that underpin the persistence of endemic diseases remains unexplored. bayesian phylogeographic frameworks that incorporate spatial heterogeneities are promising tools ...201729274171
development and evaluation of an anti-rabies virus phosphoprotein-specific monoclonal antibody for detection of rabies neutralizing antibodies using rffit.rabies is a major public health problem with a fatality rate close to 100%; however, complete prevention can be achieved through pre- or post-exposure prophylaxis. the rapid fluorescent focus inhibition test (rffit) is one of the recommended testing methods to determine the production of neutralizing antibodies after vaccination. here, we report the development of a new monoclonal antibody (mab) designed to react specifically with rabies virus (rabv) phosphoprotein (p protein), and the evaluatio ...201729267277
vaccination of dogs in an african city interrupts rabies transmission and reduces human exposure.despite the existence of effective rabies vaccines for dogs, dog-transmitted human rabies persists and has reemerged in africa. two consecutive dog vaccination campaigns took place in chad in 2012 and 2013 (coverage of 71% in both years) in the capital city of n'djaména, as previously published. we developed a deterministic model of dog-human rabies transmission fitted to weekly incidence data of rabid dogs and exposed human cases in n'djaména. our analysis showed that the effective reproductive ...201729263230
syn023, a novel humanized monoclonal antibody cocktail, for post-exposure prophylaxis of rabies.rabies is a neglected zoonotic disease that is preventable in humans by appropriate post-exposure prophylaxis (pep). however, current pep relies on polyclonal immune globulin products purified from pooled human (hrig) or equine (erig) plasma that are either in chronic shortage or in association with safety concerns. here, we present the development of an antibody cocktail, syn023, made of two novel monoclonal antibodies (mab) ctb011 and ctb012 that could serve as safer and more cost-effective al ...201729261658
genetic analysis of a rabies virus host shift event reveals within-host viral dynamics in a new host.host shift events play an important role in epizootics as adaptation to new hosts can profoundly affect the spread of the disease and the measures needed to control it. during the late 1990s, an epizootic in turkey resulted in a sustained maintenance of rabies virus (rabv) within the fox population. we used bayesian inferences to investigate whole genome sequences from fox and dog brain tissues from turkey to demonstrate that the epizootic occurred in 1997 (±1 year). furthermore, these data indi ...201729255631
seroprevalence of rabies virus antibodies in bats from high risk areas in brazilian amazonia between 2013 and 2015.the outbreaks of human rabies that occurred between 2004 and 2005 in the brazilian amazon highlight the importance of bats in the transmission of this zoonosis. ten years after, this region is still considered to be a risk area.201729237041
rabies: a novel clinical presentation.rabies is a fatal disease. saliva of a rabid dog is a rich source of rabies virus. we report a patient who suffered of rabies, who was infected by abrasion caused by the nails of a rabid dog. dogs often lick their nails and thereby transfer the rabies virus-contaminated saliva to their claws. despite treatment in our intensive care unit and application of various pharmacological antidotes, we were unable to prevent the fatal outcome.201729307972
multizonal cerebellar influence over sensorimotor areas of the rat cerebral cortex.the cerebral cortex requires cerebellar input for optimizing sensorimotor processing. however, how the sensorimotor cortex uses cerebellar information is far from understood. one critical and unanswered question is how cerebellar functional entities (zones or modules) are connected to distinct parts of the sensorimotor cortices. here, we utilized retrograde transneuronal infection of rabies virus (rabv) to study the organization of connections from the cerebellar cortex to m1, m2, and s1 of the ...201729300895
how social structure drives the population dynamics of the common vampire bat (desmodus rotundus, phyllostomidae)?social systems are major drivers of population structure and gene flow, with important effects on dynamics and dispersal of associated populations of parasites. among bats, the common vampire bat (desmodus rotundus) has likely one of the most complex social structure. using autosomal and mitochondrial markers on vampires from mexico, french guiana and north brazil, from both roosting and foraging areas, we observed an isolation by distance at the wider scale and lower but significant differentia ...201729228367
a thermostable messenger rna based vaccine against rabies.although effective rabies virus vaccines have been existing for decades, each year, rabies virus infections still cause around 50.000 fatalities worldwide. most of these cases occur in developing countries, where these vaccines are not available. the reasons for this are the prohibitive high costs of cell culture or egg grown rabies virus vaccines and the lack of a functional cold chain in many regions in which rabies virus is endemic. here, we describe the excellent temperature resistance of a ...201729216187
immunization with recombinant rabies virus expressing interleukin-18 exhibits enhanced immunogenicity and protection in mice.several studies have shown that interleukin-18 (il-18) plays an important role in both innate and adaptive immune responses. in this study, we investigated the pathogenicity and immunogenicity of recombinant rabies virus expressing il-18 (rhep-il18). experimental results showed that institute of cancer research (icr) mice that received a single intramuscular immunization with rhep-il18 elicited the highest titers of serum neutralizing antibodies and the strongest cell-mediated immune responses t ...201729207661
[expression and purification of rabies virus glycoprotein and analysis of its specific binding capacity to memory b cells].we aimed to express and purify three rabies virus glycoproteins with different tags and sizes. after analyzing their binding function, we wish to obtain a rabies virus glycoprotein with higher affinity and ability to specifically bind memory b cells. experiments were carried out to express full length, as well as the ectodomain rvg by gene engineering method. combined with the antibody of cd19 and cd27, the candidate protein labeling with fluorescence was used to analyze its binding function. fl ...201729202520
[rabies virus induces the formation of stress granules, which are in close proximity to viral factories]. 201729200383
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
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
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
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
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
pathological findings in the red fox (vulpes vulpes), stone marten (martes foina) and raccoon dog (nyctereutes procyonoides), with special emphasis on infectious and zoonotic agents in northern germany.anthropogenic landscape changes contributed to the reduction of availability of habitats to wild animals. hence, the presence of wild terrestrial carnivores in urban and peri-urban sites has increased considerably over the years implying an increased risk of interspecies spillover of infectious diseases and the transmission of zoonoses. the present study provides a detailed characterisation of the health status of the red fox (vulpes vulpes), stone marten (martes foina) and raccoon dog (nyctereu ...201728399176
serology and protein electrophoresis for evidence of exposure to 12 mink pathogens in free-ranging american mink (neovison vison) in argentina.basic pathologic characteristics for farmed minks were previously reported worldwide. however, its status in the wild has not been studied in detail.201728635524
rabies virus exposure of brazilian free-ranging wildlife from municipalities without clinical cases in humans or in terrestrial wildlife.rabies is a zoonosis that causes thousands of animal and human deaths worldwide. serological studies provide information concerning rabies virus circulation among animals and humans. we evaluated the circulation of the rabies virus in wildlife in nine municipalities of são paulo state, brazil. we took blood samples from 27 terrestrial animals of nine different mammalian species in locations without cases of rabies in human and wild terrestrial mammals. sera were tested with the use of the rapid ...201728406757
experimental infection of artibeus intermedius with a vampire bat rabies virus.experimental infection of artibeus intermedius, the great fruit-eating bat, was performed with vampire bat rabies isolates. bats (n=35) were captured in the wild and quarantined prior to experimental infection. no rabies antibodies were detected by rapid fluorescent focus inhibition test (rffit) prior to infection. three doses of rabies virus (rv) and three different routes of infection were used. one out of 35 bats died without showing any clinical signs at day 14 and was positive for rabies. n ...201728673461
natural exposure of bats in grenada to rabies virus.introduction: grenada is a rabies endemic country, where terrestrial rabies is maintained in the small indian mongoose (herpestes auropunctatus). the role of bats in the epidemiology of rabies in grenada is unknown. a 1974 report described one rabies virus positive jamaican fruit bat (artibeus jamaicensis), and a high seroprevalence in this species. in the current study, the natural exposure to rabies virus in grenadian bats was re-evaluated. it is postulated that bats serve as a natural rabies ...201728804595
ultrastructure and morphometric features of epididymal epithelium in desmodus rotundus.the blood-feeding behavior of desmodus rotundus made this bat a potential vector of rabies virus and a public health issue. consequently, the better understanding of its reproductive biology becomes valuable for the development of methods to control its population. in this study, we described morphological aspects of epithelial cells in d. rotundus' epididymis using light and transmission electron microscopy methods. the duct compartment was the main component of initial segment (83%), caput (90 ...201728869875
whole genome sequence phylogenetic analysis of four mexican rabies viruses isolated from cattle.phylogenetic analysis of the rabies virus in molecular epidemiology has been traditionally performed on partial sequences of the genome, such as the n, g, and p genes; however, that approach raises concerns about the discriminatory power compared to whole genome sequencing. in this study we characterized four strains of the rabies virus isolated from cattle in querétaro, mexico by comparing the whole genome sequence to that of strains from the american, european and asian continents. four cattle ...201728818750
genetic demography at the leading edge of the distribution of a rabies virus vector.the common vampire bat, desmodus rotundus, ranges from south america into northern mexico in north america. this sanguivorous species of bat feeds primarily on medium to large-sized mammals and is known to rely on livestock as primary prey. each year, there are hotspot areas of d. rotundus-specific rabies virus outbreaks that lead to the deaths of livestock and economic losses. based on incidental captures in our study area, which is an area of high cattle mortality from d. rotundus transmitted ...201728770072
rabies virus in bats, state of pará, brazil, 2005-2011.rabies is an acute, progressive zoonotic viral infection that in general produces a fatal outcome. this disease is responsible for deaths in humans and animals worldwide and, because it can affect all mammals, is considered one of the most important viral infections for public health. this study aimed to determine the prevalence of rabies in bats of different species found in municipalities of the state of pará from 2005 to 2011. the rabies virus was detected in 12 (0.39%) bats in a total of 310 ...201728678651
predictors and immunological correlates of sublethal mercury exposure in vampire bats.mercury (hg) is a pervasive heavy metal that often enters the environment from anthropogenic sources such as gold mining and agriculture. chronic exposure to hg can impair immune function, reducing the ability of animals to resist or recover from infections. how hg influences immunity and susceptibility remains unknown for bats, which appear immunologically distinct from other mammals and are reservoir hosts of many pathogens of importance to human and animal health. we here quantify total hg (t ...201728484633
the phylogeography of myotis bat-associated rabies viruses across canada.as rabies in carnivores is increasingly controlled throughout much of the americas, bats are emerging as a significant source of rabies virus infection of humans and domestic animals. knowledge of the bat species that maintain rabies is a crucial first step in reducing this public health problem. in north america, several bat species are known to be rabies virus reservoirs but the role of bats of the myotis genus has been unclear due to the scarcity of laboratory confirmed cases and the challeng ...201728542160
characterization of akabane virus from domestic bamboo rat, southern china.to identify the causative agents in 3 large-scale outbreaks of encephalitis and death among farmed bamboo rats (rhizomys pruinosus). the routine bacterial culture and identification were performed. there were no significant pathogenic bacteria isolated from the brain, heart, liver, spleen, lung, or kidney of diseased bamboo rats. using pcr-based methods, we excluded the following as causative agent: pox virus, herpesvirus, adenovirus, lymphocytic choriomeningitis virus, rabies virus, and sendai ...201728757035
neuropathogenesis by chandipura virus: an acute encephalitis syndrome in india.chandipura virus (chpv) has been contributing to the rising number of premature deaths due to acute encephalitis syndrome for over a decade in india. chpv belongs to the family rhabdoviridae. neuropathogenesis of chpv has been well established but the exact route of entry into the central nervous system (cns) and the triggering factor for neuronal death are still unknown. rabies virus and vesicular stomatitis virus, which are related closely to chpv, enter the cns retrogradely from peripheral or ...201728731002
genetically modified rabies virus-vectored ebola virus disease vaccines are safe and induce efficacious immune responses in mice and dogs.ebola viruses (ebovs) are zoonotic pathogens that cause ebov disease (evd) with high case fatality in humans. currently, evd vaccines are still under development in several countries. here, we generated two recombinant rabies viruses (rabvs), rerag333e/zgp and rerag333e/sgp, expressing the zaire ebov glycoprotein (zgp) or sudan ebov glycoprotein (sgp) gene based on a modified era vaccine strain (rerag333e) vector platform. the recombinant rabvs retained growth properties similar to those of the ...201728822816
evolution and antiviral specificities of interferon-induced mx proteins of bats against ebola, influenza, and other rna viruses.bats serve as a reservoir for various, often zoonotic viruses, including significant human pathogens such as ebola and influenza viruses. however, for unknown reasons, viral infections rarely cause clinical symptoms in bats. a tight control of viral replication by the host innate immune defense might contribute to this phenomenon. transcriptomic studies revealed the presence of the interferon-induced antiviral myxovirus resistance (mx) proteins in bats, but detailed functional aspects have not b ...201728490593
cloning and expression of fragment of the rabies virus nucleoprotein gene in escherichia coli and evaluation of antigenicity of the expression product.rabies virus nucleoprotein (n protein) encapsidates genomic rna of the virus and forms the viral ribonucleoprotein complex. these n proteins represent highly organized structures which activate proliferation of b cells and production antibodies against the n protein. in addition to the b cell, the rabies virus n protein has been shown to induce potent t helper cell responses resulting in a long-lasting and strong humoral immune response. rabies virus n protein is a molecular target of choice for ...201728588631
flagellin fljb as an adjuvant to the recombinant adenovirus rabies glycoprotein vaccine increases immune responses against rabies in mice.rabies virus (rabv) causes an acute progressive viral encephalitis. although currently licensed vaccines have an excellent safety and efficacy record, the development of a safer and more cost-effective vaccine is still being sought. an e1-deleted, replication-defective human adenovirus type 5 (had5) vector expressing rabv glycoprotein (had5-g) is thought to be a promising candidate vaccine for immune prophylaxis against rabies. salmonella enterica serovar typhimurium (s. typhimurium) flagellin i ...201728550434
pseudotyped lentiviral vectors for retrograde gene delivery into target brain regions.gene transfer through retrograde axonal transport of viral vectors offers a substantial advantage for analyzing roles of specific neuronal pathways or cell types forming complex neural networks. this genetic approach may also be useful in gene therapy trials by enabling delivery of transgenes into a target brain region distant from the injection site of the vectors. pseudotyping of a lentiviral vector based on human immunodeficiency virus type 1 (hiv-1) with various fusion envelope glycoproteins ...201728824385
large protein as a potential target for use in rabies diagnostics.rabies is a zoonotic viral disease that remains a serious threat to public health worldwide. the rabies lyssavirus (rabv) genome encodes five structural proteins, multifunctional and significant for pathogenicity. the large protein (l) presents well-conserved genomic regions, which may be a good alternative to generate informative datasets for development of new methods for rabies diagnosis. this paper describes the development of a technique for the identification of l protein in several rabv s ...201728854792
resurgence of rabies in hungary during 2013-2014: an attempt to track the origin of identified strains.in 2013-2014, accumulation of rabies episodes raised concerns regarding ongoing elimination programme in hungary. nearly four dozen cases were identified over a 13-month period in the central region of the country far behind the immunization zones. although the outbreak was successfully controlled, the origin of disease remained unknown. in this study, we sequenced the partial n and g genes from 47 hungarian rabies virus (rv) strains isolated from the 2013-2014 outbreak. sequencing and phylogene ...201728497505
protective immune response of oral rabies vaccine in stray dogs, corsacs and steppe wolves after a single immunization.in this study the safety and protective immunity of an oral rabies vaccine, based on the live, modified rabies virus strain vrc-rz2, was examined in stray dogs (canis sp.), corsacs (vulpes corsac) and steppe wolves (canis lupus campestris). in the safety group (dogs, n=6; corsacs, n=3; wolves, n=3) which was vaccinated with a 10-times field dose/animal, no animals showed any signs of disease or changes in behavior or appetite during the period of clinical observation, similar to the animals in t ...201728766059
a rabies virus vampire bat variant shows increased neuroinvasiveness in mice when compared to a carnivore variant.rabies is one of the most important zoonotic diseases and is caused by several rabies virus (rabv) variants. these variants can exhibit differences in neurovirulence, and few studies have attempted to evaluate the neuroinvasiveness of variants derived from vampire bats and wild carnivores. the aim of this study was to evaluate the neuropathogenesis of infection with two brazilian rabv street variants (variant 3 and crab-eating fox) in mice. balb/c mice were inoculated with rabv through the footp ...201728831620
comparison of g protein sequences of south african street rabies viruses showing distinct progression of the disease in a mouse model of experimental rabies.rabies is a fatal zoonotic disease and infections generally lead to a fatal encephalomyelitis in both humans and animals. in south africa, domestic (dogs) and the wildlife (yellow mongoose) host species maintain the canid and mongoose rabies variants respectively. in this study, pathogenicity differences of south african canid and mongoose rabies viruses were investigated in a murine model, by assessing the progression of clinical signs and survivorship. comparison of glycoprotein gene sequences ...201728627433
oral vaccination of wildlife against rabies: differences among host species in vaccine uptake efficiency.oral vaccination using attenuated and recombinant rabies vaccines has been proven a powerful tool to combat rabies in wildlife. however, clear differences have been observed in vaccine titers needed to induce a protective immune response against rabies after oral vaccination in different reservoir species. the mechanisms contributing to the observed resistance against oral rabies vaccination in some species are not completely understood. hence, the immunogenicity of the vaccine virus strain, spb ...201728641888
indigenous wildlife rabies in taiwan: ferret badgers, a long term terrestrial reservoir.the emerging disease of rabies was confirmed in taiwan ferret badgers (fbs) and reported to the world organization for animal health (oie) on july 17, 2013. the spread of wildlife rabies can be related to neighborhood countries in asia. the phylogenetic analysis was conducted by maximum likelihood (ml) methods and the bayesian coalescent approach based on the glycoprotein (g) and nucleoprotein (n) genes. the phylogeographic and spatial temporal dynamics of viral transmission were determined by u ...201728497055
processes underlying rabies virus incursions across us-canada border as revealed by whole-genome phylogeography.disease control programs aim to constrain and reduce the spread of infection. human disease interventions such as wildlife vaccination play a major role in determining the limits of a pathogen's spatial distribution. over the past few decades, a raccoon-specific variant of rabies virus (rrv) has invaded large areas of eastern north america. although expansion into canada has been largely prevented through vaccination along the us border, several outbreaks have occurred in canada. applying phylog ...201728820138
using viral gene sequences to compare and explain the heterogeneous spatial dynamics of virus epidemics.rabies is an important zoonotic disease distributed worldwide. a key question in rabies epidemiology is the identification of factors that impact virus dispersion. here we apply new analytical methods, based on phylogeographic reconstructions of viral lineage movement, to undertake a comparative evolutionary-epidemiological study of the spatial dynamics of rabies virus (rabv) epidemics in different hosts and habitats. we have compiled rabv data sets from skunk, raccoon, bat and domestic dog popu ...201728651357
rabies - epidemiology, pathogenesis, public health concerns and advances in diagnosis and control: a comprehensive review.rabies is a zoonotic, fatal and progressive neurological infection caused by rabies virus of the genus lyssavirus and family rhabdoviridae. it affects all warm-blooded animals and the disease is prevalent throughout the world and endemic in many countries except in islands like australia and antarctica. over 60,000 peoples die every year due to rabies, while approximately 15 million people receive rabies post-exposure prophylaxis (pep) annually. bite of rabid animals and saliva of infected host ...201728643547
geographical clusters and predictors of rabies in three southeastern states.the rabies virus causes progressive encephalomyelitis that is fatal in nearly 100% of untreated cases. in the united states, wildlife act as the primary reservoir for rabies; prevention, surveillance, and control costs remain high. the purpose of this study is to understand the current distribution of wildlife rabies in three southeastern states, with particular focus on raccoons as the primary eastern reservoir, as well as identify demographic and geographic factors which may affect the risk of ...201728418772
assessment of the immunogenicity of rabies vaccine preserved by vaporization and delivered to the duodenal mucosa of gray foxes (urocyon cinereoargenteus).objective to assess the immunogenicity of thermostable live-attenuated rabies virus (rabv) preserved by vaporization (pbv) and delivered to the duodenal mucosa of a wildlife species targeted for an oral vaccination program. animals 8 gray foxes (urocyon cinereoargenteus). procedures endoscopy was used to place rabv pbv (n = 3 foxes), alginate-encapsulated rabv pbv (3 foxes), or nonpreserved rabv (2 foxes) vaccine into the duodenum of foxes. blood samples were collected weekly to monitor the immu ...201728541146
whole-brain mapping of the inputs and outputs of the medial part of the olfactory tubercle.the medial part of the olfactory tubercle (ot) is a brain structure located at the interface of the reward and olfactory system. it is closely related to pheromone-rewards, natural reinforcement, addiction and many other behaviors. however, the structure of the anatomic circuitry of the medial part of the ot is still unclear. in the present study, the medial part of the ot was found to be highly connected with a wide range of brain areas with the help of the pseudorabies virus tracing tool. in o ...201728804450
longitudinal survey of two serotine bat (eptesicus serotinus) maternity colonies exposed to eblv-1 (european bat lyssavirus type 1): assessment of survival and serological status variations using capture-recapture models.this study describes two longitudinal serological surveys of european bat lyssavirus type 1 (eblv-1) antibodies in serotine bat (eptesicus serotinus) maternity colonies located in the north-east of france. this species is currently considered as the main eblv-1 reservoir. multievent capture-recapture models were used to determine the factors influencing bat rabies transmission as this method accounts for imperfect detection and uncertainty in disease states. considering the period of study, anal ...201729149215
efficacy of rabies vaccines in dogs and cats and protection in a mouse model against european bat lyssavirus type 2.rabies is preventable by pre- and/or post-exposure prophylaxis consisting of series of rabies vaccinations and in some cases the use of immunoglobulins. the success of vaccination can be estimated either by measuring virus neutralising antibodies or by challenge experiment. vaccines based on rabies virus offer cross-protection against other lyssaviruses closely related to rabies virus. the aim was to assess the success of rabies vaccination measured by the antibody response in dogs (n = 10,071) ...201728969696
integrated anatomical and physiological mapping of striatal afferent projections.the dorsomedial striatum, a key site of reward-sensitive motor output, receives extensive afferent input from cortex, thalamus and midbrain. these projections are integrated by striatal microcircuits containing both spiny projection neurons and local circuit interneurons. to explore target-cell specificity of these projections, we compared inputs onto d1-dopamine receptor positive spiny neurons, parvalbumin-positive fast-spiking interneurons and somatostatin-positive low-threshold-spiking intern ...201829359830
defining objective clusters for rabies virus sequences using affinity propagation clustering.rabies is caused by lyssaviruses, and is one of the oldest known zoonoses. in recent years, more than 21,000 nucleotide sequences of rabies viruses (rabv), from the prototype species rabies lyssavirus, have been deposited in public databases. subsequent phylogenetic analyses in combination with metadata suggest geographic distributions of rabv. however, these analyses somewhat experience technical difficulties in defining verifiable criteria for cluster allocations in phylogenetic trees inviting ...201829357361
evaluation of g2 citric acid-based dendrimer as an adjuvant in veterinary rabies vaccine.for induction of an appropriate immune response, especially in the case of an inactivated vaccine, the use of an adjuvant is crucial. in this study, adjuvanticity effect of g2 dendrimer in veterinary rabies vaccine has been investigated. a nonlinear globular g2 dendrimer comprising citric acid and polyethylene glycol 600 (peg-600) was synthesized and the toxicity was studied in vitro on the j774a.1 cell line. the adjuvanticity effect of the dendrimer was then investigated on rabies virus in nmri ...201829328884
an assessment of shedding with the oral rabies virus vaccine strain spbn gasgas in target and non-target species.a safety requirement for live vaccines is investigating possible shedding in recipients since the presence of replication competent vaccine in secretions could result in direct and indirect horizontal transmission. this is especially relevant for oral rabies vaccine baits that are deliberately distributed into the environment. in the current study, survival of an oral rabies virus vaccine, spbn gasgas, was examined in excretions from different target and non-target species; red fox, raccoon dog, ...201829325820
development of a genotype-by-sequencing immunogenetic assay as exemplified by screening for variation in red fox with and without endemic rabies exposure.pathogens are recognized as major drivers of local adaptation in wildlife systems. by determining which gene variants are favored in local interactions among populations with and without disease, spatially explicit adaptive responses to pathogens can be elucidated. much of our current understanding of host responses to disease comes from a small number of genes associated with an immune response. high-throughput sequencing (hts) technologies, such as genotype-by-sequencing (gbs), facilitate expa ...201829321894
parainfluenza virus 5-vectored vaccines against human and animal infectious diseases.parainfluenza virus 5 (piv5), known as canine parainfluenza virus in the veterinary field, is a negative-sense, nonsegmented, single-stranded rna virus belonging to the paramyxoviridae family. parainfluenza virus 5 is an excellent viral vector and has been used as a live vaccine for kennel cough for many years in dogs without any safety concern. it can grow to high titers in many cell types, and its genome is stable even in the presence of foreign gene insertions. so far, piv5 has been used to d ...201829316047
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
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
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
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
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
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
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