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in vitro and in vivo inhibition of rabies virus replication by rna interference.rabies is a zoonotic disease that affects all mammals and leads to more than 55,000 human deaths every year, caused by rabies virus (rabv) (mononegavirales: rhabdoviridae: lyssavirus). currently, human rabies treatment is based on the milwaukee protocol which consists on the induction of coma and massive antiviral therapy. the aim of this study was to assess the decrease in the titer of rabies virus both in vitro and in vivo using short-interfering rnas. to this end, three sirnas were used with ...201324516427
enhancement of blood-brain barrier permeability and reduction of tight junction protein expression are modulated by chemokines/cytokines induced by rabies virus infection.infection with laboratory-attenuated rabies virus (rabv) enhances blood-brain barrier (bbb) permeability, which has been demonstrated to be an important factor for host survival, since it allows immune effectors to enter the central nervous system (cns) and clear rabv. to probe the mechanism by which rabv infection enhances bbb permeability, the expression of tight junction (tj) proteins in the cns was investigated following intracranial inoculation with laboratory-attenuated or wild-type (wt) r ...201424522913
cxcl10 and blood-brain barrier modulation in rabies virus infection. 026895109
critical role of k1685 and k1829 in the large protein of rabies virus in viral pathogenicity and immune evasion.rabies, one of the oldest infectious diseases, still presents a public health threat in most parts of the world today. its pathogen, rabies virus (rabv), can utilize its viral proteins, such as the nucleoprotein and phosphorylation protein, to subvert the host innate immune system. for a long time, the large (l) protein was believed to be essential for rabv transcription and replication, but its role in viral pathogenicity and immune evasion was not known. recent studies have found that the cons ...201526468538
evaluation of in vitro antiviral activity of datura metel linn. against rabies virus.the soxhlet and cold extracts of datura metel linn. were evaluated for in vitro antirabies activity.027695266
persistence of rabies virus-neutralizing antibodies after vaccination of rural population following vampire bat rabies outbreak in brazil.animal control measures in latin america have decreased the incidence of urban human rabies transmitted by dogs and cats; currently most cases of human rabies are transmitted by bats. in 2004-2005, rabies outbreaks in populations living in rural brazil prompted widespread vaccination of exposed and at-risk populations. more than 3,500 inhabitants of augusto correa (pará state) received either post-exposure (pep) or pre-exposure (prep) prophylaxis. this study evaluated the persistence of rabies v ...201627653947
presence of cross-reactions with other viral encephalitides in the indirect fluorescent-antibody test for diagnosis of rabies.the antemortem diagnosis of rabies in humans employs techniques that require accuracy, speed, and sensitivity. a combination of histochemical analysis, in vitro virus isolation, immunological methods, and molecular amplification procedures are utilized in efforts to diagnose the disease. modern medicine now offers potentially life-saving treatment for a disease that was considered invariably fatal once clinical signs develop. however, medical intervention efforts require a rapid and accurate dia ...201324088851
resistance to rhabdoviridae infection and subversion of antiviral responses.interferon (ifn) treatment induces the expression of hundreds of ifn-stimulated genes (isgs). however, only a selection of their products have been demonstrated to be responsible for the inhibition of rhabdovirus replication in cultured cells; and only a few have been shown to play a role in mediating the antiviral response in vivo using gene knockout mouse models. ifns inhibit rhabdovirus replication at different stages via the induction of a variety of isgs. this review will discuss how indivi ...201526198243
ecological approaches in veterinary epidemiology: mapping the risk of bat-borne rabies using vegetation indices and night-time light satellite imagery.rabies remains a disease of significant public health concern. in the americas, bats are an important source of rabies for pets, livestock, and humans. for effective rabies control and prevention, identifying potential areas for disease occurrence is critical to guide future research, inform public health policies, and design interventions. to anticipate zoonotic infectious diseases distribution at coarse scale, veterinary epidemiology needs to advance via exploring current geographic ecology to ...201526338730
reinvestigating the role of igm in rabies virus postexposure vaccination.b cells secreting igg antibodies, but not igm, are thought to be solely responsible for vaccine-induced protection against rabies virus (rabv) infections in postexposure settings. in this report, we reinvestigated the potential for igm to mediate protection in a mouse model of rabv vaccination. immunocompetent mice immunized with an experimental live replication-deficient rabv-based vaccine produced virus neutralizing antibodies (vnas) within 3 days of vaccination. however, mice unable to produc ...201323760250
variability in seroprevalence of rabies virus neutralizing antibodies and associated factors in a colorado population of big brown bats (eptesicus fuscus).in 2001-2005 we sampled permanently marked big brown bats (eptesicus fuscus) at summer roosts in buildings at fort collins, colorado, for rabies virus neutralizing antibodies (rvna). seroprevalence was higher in adult females (17.9%, n = 2,332) than males (9.4%, n = 128; p = 0.007) or volant juveniles (10.2%, n = 738; p<0.0001). seroprevalence was lowest in a drought year with local insecticide use and highest in the year with normal conditions, suggesting that environmental stress may suppress ...201424465996
targeting dna vaccines to myeloid cells using a small peptide.targeting dna vaccines to dendritic cells (dcs) greatly enhances immunity. although several approaches have been used to target protein ags to dcs, currently there is no method that targets dna vaccines directly to dcs. here, we show that a small peptide derived from the rabies virus glycoprotein fused to protamine residues (rvg-p) can target dna to myeloid cells, including dcs, which results in enhanced humoral and t-cell responses. dcs targeted with a dna vaccine encoding the immunodominant va ...201425270431
expression of neuronal cxcl10 induced by rabies virus infection initiates infiltration of inflammatory cells, production of chemokines and cytokines, and enhancement of blood-brain barrier permeability.it has been shown that enhancement of blood-brain barrier (bbb) permeability is modulated by the expression of chemokines/cytokines and reduction of tight junction (tj) proteins in the brains of mice infected with rabies virus (rabv). since cxcl10 was found to be the most highly expressed chemokine, its temporal and spatial expression were determined in the present study. the expression of the chemokine cxcl10 was initially detected in neurons as early as 3 days postinfection (p.i.) in the brain ...201425339777
establishment of myotis myotis cell lines--model for investigation of host-pathogen interaction in a natural host for emerging viruses.bats are found to be the natural reservoirs for many emerging viruses. in most cases, severe clinical signs caused by such virus infections are normally not seen in bats. this indicates differences in the virus-host interactions and underlines the necessity to develop natural host related models to study these phenomena. due to the strict protection of european bat species, immortalized cell lines are the only alternative to investigate the innate anti-virus immune mechanisms. here, we report ab ...201425295526
molecular evolutionary signatures reveal the role of host ecological dynamics in viral disease emergence and spread.rna viruses account for numerous emerging and perennial infectious diseases, and are characterized by rapid rates of molecular evolution. the ecological dynamics of most emerging rna viruses are still poorly understood and difficult to ascertain. the availability of genome sequence data for many rna viruses, in principle, could be used to infer ecological dynamics if changes in population numbers produced a lasting signature within the pattern of genome evolution. as a result, the rapidly emergi ...201323382419
rabies in iraq: trends in human cases 2001-2010 and characterisation of animal rabies strains from baghdad.control of rabies requires a consistent supply of dependable resources, constructive cooperation between veterinary and public health authorities, and systematic surveillance. these are challenging in any circumstances, but particularly during conflict. here we describe available human rabies surveillance data from iraq, results of renewed sampling for rabies in animals, and the first genetic characterisation of circulating rabies strains from iraq. human rabies is notifiable, with reported case ...201323469303
efficacy of favipiravir (t-705) in rabies postexposure prophylaxis.rabies is a fatal encephalitis caused by rabies virus (rabv), and no antiviral drugs for rabv are currently available. we report for the first time the efficacy of favipiravir (t-705) against rabv in vitro and in vivo. t-705 produced a significant, 3-4 log10 reduction in the multiplication of street and fixed rabv strains in mouse neuroblastoma neuro-2a cells, with half-maximal inhibitory concentrations of 32.4 µm and 44.3 µm, respectively. t-705 significantly improved morbidity and mortality am ...201526655300
interferon-induced protein ifit2 protects mice from infection of the peripheral nervous system by vesicular stomatitis virus.the interferon system provides the first line of host defense against virus infection. mouse pathogenesis studies have revealed the importance of specific interferon-induced proteins in providing protection against specific viruses. we have previously reported that one such protein, ifit2, protects neurons of the central nervous system from intranasal infection by the neurotropic rhabdovirus, vesicular stomatitis virus (vsv). here, we demonstrate that ifit2 protects the peripheral nervous system ...201424991014
met-ccl5 represents an immunotherapy strategy to ameliorate rabies virus infection.infection of rabies virus (rabv) causes central nervous system (cns) dysfunction and results in high mortality in human and animals. however, it is still unclear whether and how cns inflammation and immune response contribute to rabv infection.201425182681
explaining the geographic spread of emerging epidemics: a framework for comparing viral phylogenies and environmental landscape data.phylogenetic analysis is now an important tool in the study of viral outbreaks. it can reconstruct epidemic history when surveillance epidemiology data are sparse, and can indicate transmission linkages among infections that may not otherwise be evident. however, a remaining challenge is to develop an analytical framework that can test hypotheses about the effect of environmental variables on pathogen spatial spread. recent phylogeographic approaches can reconstruct the history of virus dispersa ...201626864798
probable rabies virus transmission through organ transplantation, china, 2015.during july 2015, physicians at a hospital in beijing, china, diagnosed rabies in 2 patients who had each received a kidney from a common organ donor who had died from acute progressive encephalitis of unknown cause. the patients had rabies incubation periods of 42 and 48 days. altered mental status developed in both patients and progressively worsened to deep coma within 80 days after transplantation; both patients died. two other transplant recipients received corneas but remained well after r ...201627331337
genome-wide transcriptional profiling reveals two distinct outcomes in central nervous system infections of rabies virus.rabies remains a major public health concern in many developing countries. the precise neuropathogenesis of rabies is unknown, though it is hypothesized to be due to neuronal death or dysfunction. mice that received intranasal inoculation of an attenuated rabies virus (rabv) strain hep-flury exhibited subtle clinical signs, and eventually recovered, which is different from the fatal encephalitis caused by the virulent rabv strain cvs-11. to understand the neuropathogenesis of rabies and the mech ...201627242764
biochemical and biophysical characterization of cell-free synthesized rift valley fever virus nucleoprotein capsids enables in vitro screening to identify novel antivirals.viral capsid assembly involves the oligomerization of the capsid nucleoprotein (np), which is an essential step in viral replication and may represent a potential antiviral target. an in vitro transcription-translation reaction using a wheat germ (wg) extract in combination with a sandwich elisa assay has recently been used to identify small molecules with antiviral activity against the rabies virus.201627179769
subversion of the immune response by rabies virus.rabies has affected mankind for several centuries and is one of the oldest known zoonoses. it is peculiar how little is known regarding the means by which rabies virus (rabv) evades the immune response and kills its host. this review investigates the complex interplay between rabv and the immune system, including the various means by which rabv evades, or advantageously utilizes, the host immune response in order to ensure successful replication and spread to another host. different factors that ...201627548204
molecular and cellular aspects of rhabdovirus entry.rhabdoviruses enter the cell via the endocytic pathway and subsequently fuse with a cellular membrane within the acidic environment of the endosome. both receptor recognition and membrane fusion are mediated by a single transmembrane viral glycoprotein (g). fusion is triggered via a low-ph induced structural rearrangement. g is an atypical fusion protein as there is a ph-dependent equilibrium between its pre- and post-fusion conformations. the elucidation of the atomic structures of these two co ...201222355455
elucidating the phylodynamics of endemic rabies virus in eastern africa using whole-genome sequencing.many of the pathogens perceived to pose the greatest risk to humans are viral zoonoses, responsible for a range of emerging and endemic infectious diseases. phylogeography is a useful tool to understand the processes that give rise to spatial patterns and drive dynamics in virus populations. increasingly, whole-genome information is being used to uncover these patterns, but the limits of phylogenetic resolution that can be achieved with this are unclear. here, whole-genome variation was used to ...201527774283
herbal plants and plant preparations as remedial approach for viral diseases.herbal plants, plant preparations and phytoconstituents have proved useful in attenuating infectious conditions and were the only remedies available, till the advent of antibiotics (many being of plant origin themselves). among infectious diseases, viral diseases in particular, remain the leading cause of death in humans globally. a variety of phytoconstituents derived from medicinal herbs have been extensively studied for antiviral activity. based on this rationale, an online search was perform ...201526645032
presence of virus neutralizing antibodies in cerebral spinal fluid correlates with non-lethal rabies in dogs.rabies is traditionally considered a uniformly fatal disease after onset of clinical manifestations. however, increasing evidence indicates that non-lethal infection as well as recovery from flaccid paralysis and encephalitis occurs in laboratory animals as well as humans.201324069466
rates of viral evolution are linked to host geography in bat rabies.rates of evolution span orders of magnitude among rna viruses with important implications for viral transmission and emergence. although the tempo of viral evolution is often ascribed to viral features such as mutation rates and transmission mode, these factors alone cannot explain variation among closely related viruses, where host biology might operate more strongly on viral evolution. here, we analyzed sequence data from hundreds of rabies viruses collected from bats throughout the americas t ...201222615575
assessment of packed bed bioreactor systems in the production of viral vaccines.vaccination is believed to be the most effective method for the prevention of infectious diseases. thus it is imperative to develop cost effective and scalable process for the production of vaccines so as to make them affordable for mass use. in this study, performance of a novel disposable icellis fixed bed bioreactor system was investigated for the production of some viral vaccines like rabies, hepatitis-a and chikungunya vaccines in comparison to conventional systems like the commercially ava ...201424949260
twenty year experience of the oral rabies vaccine sag2 in wildlife: a global review.the sag2 vaccine (rabigen® sag2) is a modified live attenuated rabies virus vaccine, selected from the sad bern strain in a two-step process of amino acid mutation using neutralizing monoclonal antibodies. the strain is genetically stable and does not spread in vivo or induce a persistent infection. its absence of residual pathogenicity was extensively demonstrated in multiple target and non target species (such as wild carnivores and rodent species), including non-human primates. the efficacy o ...201425106552
development of primer pairs from molecular typing of rabies virus variants present in mexico.nucleoprotein (n) gene from rabies virus (rabv) is a useful sequence target for variant studies. several specific rabv variants have been characterized in different mammalian hosts such as skunk, dog, and bats by using anti-nucleocapsid monoclonal antibodies (mabs) via indirect fluorescent antibody (ifa) test, a technique not available in many laboratories in mexico. in the present study, a total of 158 sequences of n gene from rabv were used to design eight pairs of primers (four external and f ...201627563666
an mrna vaccine encoding rabies virus glycoprotein induces protection against lethal infection in mice and correlates of protection in adult and newborn pigs.rabies is a zoonotic infectious disease of the central nervous system (cns). in unvaccinated or untreated subjects, rabies virus infection causes severe neurological symptoms and is invariably fatal. despite the long-standing existence of effective vaccines, vaccine availability remains insufficient, with high numbers of fatal infections mostly in developing countries. nucleic acid based vaccines have proven convincingly as a new technology for the fast development of vaccines against newly emer ...201627336830
foraging choices of vampire bats in diverse landscapes: potential implications for land-use change and disease transmission.in latin america, the common vampire bat desmodus rotundus is the primary reservoir of rabies, a zoonotic virus that kills thousands of livestock annually and causes sporadic and lethal human rabies outbreaks. the proliferation of livestock provides an abundant food resource for this obligate blood-feeding species that could alter its foraging behaviour and rabies transmission, but poor understanding of the dietary plasticity of vampire bats limits understanding of how livestock influences rabie ...201627499553
rabies surveillance in the united states during 2013.during 2013, 53 reporting jurisdictions reported 5,865 rabid animals and 3 human rabies cases to the cdc, representing a 4.8% decrease from the 6,162 rabid animals and 1 human case reported in 2012. ninety-two percent of reported rabid animals were wildlife. relative contributions by the major animal groups were as follows: 1,898 raccoons (32.4%), 1,598 bats (27.2%), 1,447 skunks (24.7%), 344 foxes (5.9%), 247 cats (4.2%), 86 cattle (1.5%), and 89 dogs (1.5%). one human case was reported from ma ...025356711
comparison of biotinylated monoclonal and polyclonal antibodies in an evaluation of a direct rapid immunohistochemical test for the routine diagnosis of rabies in southern africa.the major etiological agent of rabies, rabies virus (rabv), accounts for tens of thousands of human deaths per annum. the majority of these deaths are associated with rabies cycles in dogs in resource-limited countries of africa and asia. although routine rabies diagnosis plays an integral role in disease surveillance and management, the application of the currently recommended direct fluorescent antibody (dfa) test in countries on the african and asian continents remains quite limited. a novel ...201425254652
spatio-temporal analysis of the genetic diversity of arctic rabies viruses and their reservoir hosts in greenland.there has been limited knowledge on spatio-temporal epidemiology of zoonotic arctic fox rabies among countries bordering the arctic, in particular greenland. previous molecular epidemiological studies have suggested the occurrence of one particular arctic rabies virus (rabv) lineage (arctic-3), but have been limited by a low number of available samples preventing in-depth high resolution phylogenetic analysis of rabvs at that time. however, an improved knowledge of the evolution, at a molecular ...201627459154
companion animals as a source of viruses for human beings and food production animals.companion animals comprise a wide variety of species, including dogs, cats, horses, ferrets, guinea pigs, reptiles, birds and ornamental fish, as well as food production animal species, such as domestic pigs, kept as companion animals. despite their prominent place in human society, little is known about the role of companion animals as sources of viruses for people and food production animals. therefore, we reviewed the literature for accounts of infections of companion animals by zoonotic viru ...201627522300
beyond rabies: are free-ranging skunks (mephitis mephitis) in british columbia reservoirs of emerging infection?wild animal reservoirs are an important source of emerging and zoonotic infection. skunks (mephitis mephitis) are a reservoir of skunk strain rabies virus in canada, with the exception of some areas including the province of british columbia (bc). beyond rabies, the reservoir status of skunks for emerging and zoonotic pathogens in bc is unknown. from march 2011 to february 2015, 50 free-ranging skunks were necropsied and tested for 4 pathogens: influenza a, aleutian disease virus (adv), leptospi ...201726392297
serosurvey for selected pathogens in free-ranging american black bears (ursus americanus) in maryland, usa.american black bears (ursus americanus) in maryland, usa, live in forested areas in close proximity to humans and their domestic pets. from 1999 to 2011, we collected 84 serum samples from 63 black bears (18 males; 45 females) in five maryland counties and tested them for exposure to infectious, including zoonotic, pathogens. a large portion of the bears had antibody to canine distemper virus and toxoplasma gondii, many at high titers. prevalences of antibodies to zoonotic agents such as rabies ...201425075540
using open-access taxonomic and spatial information to create a comprehensive database for the study of mammalian and avian livestock and pet infections.what are all the species of pathogen that affect our livestock? as 6 out of every 10 human pathogens came from animals, with a good number from livestock and pets, it seems likely that the majority that emerge in the future, and which could threaten or devastate human health, will come from animals. only 10 years ago, the first comprehensive pathogen list was compiled for humans; we still have no equivalent for animals. here we describe the creation of a novel pathogen database, and present outp ...201423906393
first report of angiostrongylus vasorum and hepatozoon from a red fox (vulpes vulpes) from west virginia, usa.angiostrongylus vasorum was identified in the lungs of a red fox (vulpes vulpes) from west virginia, united states (us), indicating a new geographical location for this metastrongylid nematode. the fox was euthanized and submitted for necropsy after displaying erratic behavior. we did not detect rabies virus or canine distemper virus from the fox. we observed bronchopneumonia associated with a. vasorum infection disseminated in both lungs. in addition, protozoal meronts were observed in the live ...201424412356
[rabies in bats].rabies is a zoonosis ending fatally in all mammals, including humans. unlike the other mammals, this disease is usually not fatal in bats. rabies is caused by lyssaviruses which are divided into several distinct phylogroups comprising 15 known viruses. it is believed that the original hosts of all lyssaviruses are bats. classical rabies virus (rabv) occurs in bats across americas and represents the major cause of rabies in humans and domestic animals there. european bat lyssavirus type 1 (eblv-1 ...201627450525
analysis of the complete genome of the first irkut virus isolate from china: comparison across the lyssavirus genus.the genome of irkut virus, isolate irkv-thchina12, the first non-rabies lyssavirus from china (of bat origin), has been completely sequenced. in general, coding and non-coding regions of this viral genome are similar to those of other lyssaviruses. however, alignment of the deduced amino acid sequences of the structural proteins of irkv-thchina12 with those of other lyssavirus representatives revealed significant variability between viral species. the nucleoprotein and matrix protein were found ...201323872529
potential exposures to australian bat lyssavirus notified in queensland, australia, 2009-2014.australian bat lyssavirus (ablv) belongs to the genus lyssavirus which also includes classic rabies virus and the european lyssaviruses. to date, the only three known human ablv cases, all fatal, have been reported from queensland, australia. ablv is widely distributed in australian bats, and any bite or scratch from an australian bat is considered a potential exposure to ablv.201628033365
cross-neutralization of antibodies induced by vaccination with purified chick embryo cell vaccine (pcecv) against different lyssavirus species.rabies is a neglected zoonotic disease caused by viruses belonging to the genus lyssavirus. in endemic countries of asia and africa, where the majority of the estimated 60,000 human rabies deaths occur, it is mainly caused by the classical rabies virus (rabv) transmitted by dogs. over the last decade new species within the genus lyssavirus have been identified. meanwhile 15 (proposed or classified) species exist, including australian bat lyssavirus (ablv), european bat lyssavirus (eblv-1 and -2) ...201425483634
recent observations on australian bat lyssavirus tropism and viral entry.australian bat lyssavirus (ablv) is a recently emerged rhabdovirus of the genus lyssavirus considered endemic in australian bat populations that causes a neurological disease in people indistinguishable from clinical rabies. there are two distinct variants of ablv, one that circulates in frugivorous bats (genus pteropus) and the other in insectivorous microbats (genus saccolaimus). three fatal human cases of ablv infection have been reported, the most recent in 2013, and each manifested as acute ...201424556791
travel and non-travel associated rabies post exposure treatment in new south wales residents, australia, 2007-2011: a cross-sectional analysis.australian bat lyssavirus is endemic in australian bats. more australians are travelling to rabies (lyssavirus 1) endemic countries. the nature and frequency of lyssavirus exposures and characteristics of new south wales (nsw) residents exposed have not previously been described.201324211239
host cell tropism mediated by australian bat lyssavirus envelope glycoproteins.australian bat lyssavirus (ablv) is a rhabdovirus of the lyssavirus genus capable of causing fatal rabies-like encephalitis in humans. there are two variants of ablv, one circulating in pteropid fruit bats and another in insectivorous bats. three fatal human cases of ablv infection have been reported with the third case in 2013. importantly, two equine cases also arose in 2013; the first occurrence of ablv in a species other than bats or humans. we examined the host cell entry of ablv, character ...201323849788
black-backed jackal exposure to rabies virus, canine distemper virus, and bacillus anthracis in etosha national park, namibia.canine distemper virus (cdv) and rabies virus (rabv) occur worldwide in wild carnivore and domestic dog populations and pose threats to wildlife conservation and public health. in etosha national park (enp), namibia, anthrax is endemic and generates carcasses frequently fed on by an unusually dense population of black-backed jackals (canis mesomelas). using serology, phylogenetic analyses (on samples obtained from february 2009-july 2010), and historical mortality records (1975-2011), we assesse ...201222493112
bacillus atrophaeus inactivated spores as a potential adjuvant for veterinary rabies vaccine.rabies is a viral encephalitis, nearly always fatal, but preventable through vaccines. rabid animal bite is the prime transmission act, while veterinary vaccination is one of the best strategies for rabies general prevention. aluminum compounds and saponin are the commercial adjuvants used for this vaccine nowadays. nevertheless, aluminum compounds can provoke undesired side effects and saponin has a narrow activity range without toxicity. b. atrophaeus inactivated spores (bais), with or without ...201222449426
health survey of free-ranging raccoons (procyon lotor) in central park, new york, new york, usa: implications for human and domestic animal health.we conducted health assessments on 113 free-ranging raccoons ( procyon lotor ) in central park, new york city, us, in february 2010, september 2010, and november 2011 in conjunction with a trap-vaccinate-release program to control a raccoon rabies epizootic. five individuals were sampled at two time points for 118 raccoon examinations in total. we tested 13 of 13 and 8 of 13 euthanized raccoons for rabies and canine distemper virus (cdv), respectively, by antigen testing on brain tissue; all wer ...201728135131
intranasal location and immunohistochemical characterization of the equine olfactory epithelium.the olfactory epithelium (oe) is the only body site where neurons contact directly the environment and are therefore exposed to a broad variation of substances and insults. it can serve as portal of entry for neurotropic viruses which spread via the olfactory pathway to the central nervous system. for horses, it has been proposed and concluded mainly from rodent studies that different viruses, e.g., borna disease virus, equine herpesvirus 1 (ehv-1), hendra virus, influenza virus, rabies virus, v ...201627790096
transolfactory neuroinvasion by viruses threatens the human brain.viral neuroinvasion via the olfactory system has been investigated in a variety of virus-animal models by scientists in many fields including virologists, pathologists, and neurologists. in humans, herpes simplex virus type 1 (hsv-1), human herpesvirus 6 (hhv-6), borna disease virus, rabies virus, and influenza a virus have been shown to take the olfactory route for neuroinvasion based on forensic and post-mortem specimens. this article briefly summarizes the anatomy, physiology, and immunology ...201526666182
unilateral cerebellar hypoplasia and mesencephalic malformation in a hanoverian foal.neurological cases, especially in foals, are rare in the daily practical work. the most common causes are traumata and infectious diseases of the central nervous system (cns). this case report provides further insights into the wide spectrum of possible neuropathological lesions by detailing a complex malformation with unilateral neurological signs that occurred later post natum. thus, clinicians should also be aware of malformations in case of respective neurological patients. a hanoverian foal ...201323608891
a rabies vaccine adjuvanted with saponins from leaves of the soap tree (quillaja brasiliensis) induces specific immune responses and protects against lethal challenge.quillaja brasiliensis (quillajaceae) is a saponin producing species native from southern brazil and uruguay. its saponins are remarkably similar to those of q. saponaria, which provides most of the saponins used as immunoadjuvants in vaccines. the immunostimulating capacities of aqueous extract (ae) and purified saponin fraction (qb-90) obtained from leaves of q. brasiliensis were favorably comparable to those of a commercial saponin-based adjuvant preparation (quil-a) in experimental vaccines a ...201627032516
molecular characterization of encephalitic bovine listeriosis from southern brazil.reports of bovine listeriosis in brazil are uncommon, being restricted to citations within retrospective studies, resulting in scarce documented information of this important disease of cattle. this manuscript describes the molecular findings associated with spontaneous encephalitic listeriosis in two steers from distinct herds within the state of paraná, southern brazil. both animals demonstrated altered consciousness suggestive of brain stem dysfunctions and died a few days after the initial o ...201423832703
[development and preliminary assessment of a recombinant canarypox virus as an antirabic vaccine candidate].development and preliminary assessment of a recombinant canarypox virus as an antirabic vaccine candidate. in argentina, rabies is limited to some northern provinces. availability of new vaccines abolishing the handling of the rabies virus and allowing disease control has regional and national strategic importance. vaccines based on recombinant poxviruses have been successfully used as antirabic vaccines worldwide. although these systems are not commercially available, the platform to obtain rec ...201222997764
exposure to selected pathogens in to selected pathogens in geoffroy's cats and domestic carnivores from central argentina.wild carnivores share a high percentage of parasites and viruses with closely related domestic carnivores. because of increased overlap and potential contact with domestic species, we conducted a retrospective serosurvey for 11 common carnivore pathogens in 40 geoffroy's cats (leopardus geoffroyi) sampled between 2000 and 2008 within or near two protected areas in central argentina (lihué calel national park, la pampa, and campos del tuyú national park, buenos aires), as well as five domestic ca ...201223060491
inactivated recombinant rabies viruses displaying canine distemper virus glycoproteins induce protective immunity against both pathogens.the development of multivalent vaccines is an attractive methodology for the simultaneous prevention of several infectious diseases in vulnerable populations. both canine distemper virus (cdv) and rabies virus (rabv) cause lethal disease in wild and domestic carnivores. while rabv vaccines are inactivated, the live-attenuated cdv vaccines retain residual virulence for highly susceptible wildlife species. in this study, we developed recombinant bivalent vaccine candidates based on recombinant vac ...201728148801
canine distemper in endangered ethiopian wolves.the ethiopian wolf (canis simensis) is the world's rarest canid; ≈500 wolves remain. the largest population is found within the bale mountains national park (bmnp) in southeastern ethiopia, where conservation efforts have demonstrated the negative effect of rabies virus on wolf populations. we describe previously unreported infections with canine distemper virus (cdv) among these wolves during 2005-2006 and 2010. death rates ranged from 43% to 68% in affected subpopulations and were higher for s ...201525898177
a recombinant canine distemper virus expressing a modified rabies virus glycoprotein induces immune responses in mice.canine distemper virus (cdv) and rabies virus (rv) are two important pathogens of the dog. cdv, a member of the morbillivirus genus, has shown promise as an expression vector. the glycoprotein from rv is a main contributor to protective immunity and capable of eliciting the production of virus-neutralizing antibodies. in this study, we recovered an attenuated strain of canine distemper virus and constructed a recombinant virus, rcdv-rv-g, expressing a modified (r333q) rabies virus glycoprotein ( ...201525764477
recombinant rabies virus expressing the h protein of canine distemper virus protects dogs from the lethal distemper challenge.the rabies virus (rv) vector lbnse expressing foreign antigens have shown considerable promise as vaccines against viral and bacteria diseases, which is effective and safe. we produced a new rv-based vaccine vehicle expressing 1.824 kb hemagglutinin (h) gene of the canine distemper virus (cdv) by reverse genetics technology. the recombinant virus lbnse-cdv-h retained growth properties similar to those of vector lbnse both in bsr and mna cell culture. the h gene of cdv was expressed and detected ...201425465178
serologic survey for cross-species pathogens in urban coyotes (canis latrans), colorado, usa.abstract as coyotes (canis latrans) adapt to living in urban environments, the opportunity for cross-species transmission of pathogens may increase. we investigated the prevalence of antibodies to pathogens that are either zoonotic or affect multiple animal species in urban coyotes in the denver metropolitan area, colorado, usa, in 2012. we assayed for antibodies to canine parvovirus-2, canine distemper virus, rabies virus, toxoplasma gondii, yersinia pestis, and serotypes of leptospira interrog ...201425121408
selection of an aptamer against rabies virus: a new class of molecules with antiviral activity.rabies is a fatal central nervous system (cns) disease caused by the neurotropic rabies virus (rabv). the therapeutic management of rabv infections is still problematic, and novel antiviral strategies are urgently required. we established the rvg-bhk-21 cell line, which expresses rabv glycoprotein on the cell surface, to select aptamers. through 28 iterative rounds of selection, single-stranded dna (ssdna) aptamers were generated by exponential enrichment (selex). a virus titer assay and a real- ...201424486485
high prevalence of antibodies against canine adenovirus (cav) type 2 in domestic dog populations in south africa precludes the use of cav-based recombinant rabies vaccines.rabies in dogs can be controlled through mass vaccination. oral vaccination of domestic dogs would be useful in the developing world, where greater vaccination coverage is needed especially in inaccessible areas or places with large numbers of free-roaming dogs. from this perspective, recent research has focused on development of new recombinant vaccines that can be administered orally in a bait to be used as adjunct for parenteral vaccination. one such candidate, a recombinant canine adenovirus ...201323867013
rabies, canine distemper, and canine parvovirus exposure in large carnivore communities from two zambian ecosystems.disease transmission within and among wild and domestic carnivores can have significant impacts on populations, particularly for threatened and endangered species. we used serology to evaluate potential exposure to rabies virus, canine distemper virus (cdv), and canine parvovirus (cpv) for populations of african lions (panthera leo), african wild dogs (lycaon pictus), and spotted hyenas (crocuta crocuta) in zambia's south luangwa national park (slnp) and liuwa plain national park (lpnp) as well ...201323805791
serosurvey for selected viral infections in free-ranging jaguars (panthera onca) and domestic carnivores in brazilian cerrado, pantanal, and amazon.we investigated the exposure of jaguar (panthera onca) populations and domestic carnivores to selected viral infections in the cerrado, amazon, and pantanal biomes of brazil. between february 2000 and january 2010, we collected serum samples from 31 jaguars, 174 dogs (canis lupus familiaris), and 35 domestic cats (felis catus). serologic analyses for antibodies to rabies virus, canine distemper virus (cdv), feline immunodeficiency virus (fiv), and for feline leukemia virus (felv) antigen were co ...201323778599
aptamers targeting rabies virus-infected cells inhibit viral replication both in vitro and in vivo.rabies is an acute fatal encephalitis disease that affects many warm-blooded mammals. the causative agent of the disease is rabies virus (rabv). currently, no approved therapy is available once the clinical signs have appeared. aptamers, oligonucleotide ligands capable of binding a variety of molecular targets with high affinity and specificity, have recently emerged as promising therapeutic agents. in this study, sixteen high-affinity single-stranded dna (ssdna) aptamers were generated by cell- ...201323333291
recombinant canine distemper virus serves as bivalent live vaccine against rabies and canine distemper.effective, safe, and affordable rabies vaccines are still being sought. attenuated live vaccine has been widely used to protect carnivores from canine distemper. in this study, we generated a recombinant canine distemper virus (cdv) vaccine strain, rcdv-rvg, expressing the rabies virus glycoprotein (rvg) by using reverse genetics. the recombinant virus rcdv-rvg retained growth properties similar to those of vector cdv in vero cell culture. animal studies demonstrated that rcdv-rvg was safe in mi ...201222698451
experimental oral immunization of ferret badgers (melogale moschata) with a recombinant canine adenovirus vaccine cav-2-e3δ-rgp and an attenuated rabies virus srv9.ferret badgers (melogale moschata) are a major reservoir of rabies virus in southeastern china. oral immunization has been shown to be a practical method for wildlife rabies management in europe and north america. two groups of 20 ferret badgers were given a single oral dose of a recombinant canine adenovirus-rabies vaccine, cav-2-e3δ-rgp, or an experimental attenuated rabies virus vaccine, srv9. at 21 days, all ferret badgers had seroconverted, with serum virus-neutralizing antibodies ranging f ...201424506428
two potential recombinant rabies vaccines expressing canine parvovirus virion protein 2 induce immunogenicity to canine parvovirus and rabies virus.both rabies virus (rabv) and canine parvovirus (cpv) cause lethal diseases in dogs. in this study, both high egg passage flury (hep-flury) strains of rabv and recombinant rabv carrying double rabv glycoprotein (g) gene were used to express the cpv virion protein 2 (vp2) gene, and were designated rhep-vp2 and, rhep-dg-vp2 respectively. the two recombinant rabvs maintained optimal virus titration according to their viral growth kinetics assay compared with the parental strain hep-flury. western bl ...201627449079
a retrospective study of brain lesions in goats submitted to three veterinary diagnostic laboratories.a retrospective study of brain lesions in goats was conducted to identify the range of lesions and diseases recognized and to make recommendations regarding the best tissues to examine and tests to conduct in order to maximize the likelihood of making a definitive diagnosis in goats that may have had clinical signs referable to the brain. one hundred thirty-nine goats with a brain lesion were identified. the most common lesion, in 52.5% of the goats, was suppurative inflammation. approximately t ...201323794017
the olfactory nerve: a shortcut for influenza and other viral diseases into the central nervous system.the olfactory nerve consists mainly of olfactory receptor neurons and directly connects the nasal cavity with the central nervous system (cns). each olfactory receptor neuron projects a dendrite into the nasal cavity on the apical side, and on the basal side extends its axon through the cribriform plate into the olfactory bulb of the brain. viruses that can use the olfactory nerve as a shortcut into the cns include influenza a virus, herpesviruses, poliovirus, paramyxoviruses, vesicular stomatit ...201525294743
the antiviral innate immune response in fish: evolution and conservation of the ifn system.innate immunity constitutes the first line of the host defense after pathogen invasion. viruses trigger the expression of interferons (ifns). these master antiviral cytokines induce in turn a large number of interferon-stimulated genes, which possess diverse effector and regulatory functions. the ifn system is conserved in all tetrapods as well as in fishes, but not in tunicates or in the lancelet, suggesting that it originated in early vertebrates. viral diseases are an important concern of fis ...201324075867
development of infectious clones of a wild-type korean rabies virus and evaluation of their pathogenic potential.most reverse genetic (rg) systems for rabies viruses (rvs) have been constructed on the genome background of laboratory-adapted strains. in this study, we developed an rg system using a korean wild type (kgh) strain to investigate the pathogenic potential of different strains. we developed a rg system with the kgh strain for the first time. following the complete genome sequencing of the kgh strain, pkgh infectious clones were constructed using the cmv/t7 promoter, and hamrz and hdvrz were intro ...201627397101
recent advances in the development of vaccines for ebola virus disease.ebola virus is one of the most dangerous microorganisms in the world causing hemorrhagic fevers in humans and non-human primates. ebola virus (ebov) is a zoonotic infection, which emerges and re-emerges in human populations. the 2014 outbreak was caused by the zaire strain, which has a kill rate of up to 90%, though 40% was recorded in the current outbreak. the 2014 outbreak is larger than all 20 outbreaks that have occurred since 1976, when the virus was first discovered. it is the first time t ...201626596227
ebolavirus vaccines: progress in the fight against ebola virus disease.ebolaviruses are highly infectious pathogens that cause lethal ebola virus disease (evd) in humans and non-human primates (nhps). due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. in this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vacc ...201526535889
rabies-virus-glycoprotein-pseudotyped recombinant baculovirus vaccine confers complete protection against lethal rabies virus challenge in a mouse model.rabies virus has been an ongoing threat to humans and animals. here, we developed a new strategy to generate a rabies virus vaccine based on a pseudotyped baculovirus. the recombinant baculovirus (bv-rvg/rvg) was pseudotyped with the rabies virus glycoprotein (rvg) and also simultaneously expressed another rvg under the control of the immediate early cmv promoter. in vitro, this rvg-pseudotyped baculovirus vector induced syncytium formation in insect cells and displayed more efficient gene deliv ...201424793501
development of a reverse genetics system for the ag strain of rabies virus in china.the ag rabies virus strain has been attenuated through multiple passages in cells and is now used as a vaccine strain in china. we attempted to develop a reverse genetics system using the ag strain. recombinant full-length genomic cdna was flanked by a hammerhead ribozyme and the hepatitis delta virus ribozyme. three helper plasmids encoding the nucleoprotein, the phosphoprotein, and the large protein were produced and introduced together with a plasmid containing the full-length ag viral genome ...201424272786
cationic amphiphilic drugs enhance entry of lentiviral particles pseudotyped with rabies virus glycoprotein into non-neuronal cells.amiodarone and other cationic amphiphilic drugs (cads) inhibit cell entry by diverse human pathogenic viruses including filoviruses, dengue virus and japanese encephalitis virus. they are thus considered potential broad spectrum antiviral agents. here we report the unexpected finding that amiodarone and other cads markedly enhance rabies virus (rabv) glycoprotein- (gp-) mediated cell entry of pseudotyped lentiviruses into non-neuronal cells but not in neuronal cells. increased cell entry can als ...201526542648
serological evidence of lyssaviruses among bats on southwestern indian ocean islands.we provide serological evidence of lyssavirus circulation among bats on southwestern indian ocean (swio) islands. a total of 572 bats belonging to 22 species were collected on anjouan, mayotte, la réunion, mauritius, mahé and madagascar and screened by the rapid fluorescent focus inhibition test for the presence of neutralising antibodies against the two main rabies related lyssaviruses circulating on the african continent: duvenhage lyssavirus (duvv) and lagos bat lyssavirus (lbv), representing ...201627501458
antigenic characterisation of lyssaviruses in south africa.there are at least six lyssavirus species that have been isolated in africa, which include classical rabies virus, lagos bat virus, mokola virus, duvenhage virus, shimoni bat virus and ikoma lyssavirus. in this retrospective study, an analysis of the antigenic reactivity patterns of lyssaviruses in south africa against a panel of 15 anti-nucleoprotein monoclonal antibodies was undertaken. a total of 624 brain specimens, collected between 2005 and 2009, confirmed as containing lyssavirus antigen ...201425685866
interaction of rabies virus p-protein with stat proteins is critical to lethal rabies disease.rabies virus (rabv) causes rabies disease resulting in >55,000 human deaths/year. the multifunctional rabv p-protein has essential roles in genome replication, and forms interactions with cellular stat proteins that are thought to underlie viral antagonism of interferon-dependent immunity. however, the molecular details of p-protein-stat interaction, and its importance to disease are unresolved.201424367042
comparison of pathogenic domains of rabies and african rabies-related lyssaviruses and pathogenicity observed in mice.several lyssavirus species occur in africa (rabies virus, lagos bat virus, mokola virus, duvenhage virus, shimoni bat virus and ikoma lyssavirus), displaying a high sequence diversity between isolates belonging to the same species. there is limited information about comparative pathogenesis of these african lyssaviruses and this precludes authoritative opinion on the potential public and veterinary health impact. in this study, an analysis of representative african lyssaviruses attempted to corr ...201323718883
in vitro and in vivo isolation and characterization of duvenhage virus.a fatal human case of duvenhage virus (duvv) infection in a dutch traveller who had returned from kenya was reported in 2007. she exhibited classical symptoms of rabies encephalitis with distinct pathological findings. in the present study we describe the isolation and characterization of duvv in vitro and its passage in balb/c mice. the virus proved to be neuroinvasive in both juvenile and adult mice, resulting in about 50% lethality upon peripheral infection. clinical signs in infected mice we ...201222654660
the final (oral ebola) vaccine trial on captive chimpanzees?could new oral vaccine technologies protect endangered wildlife against a rising tide of infectious disease? we used captive chimpanzees to test oral delivery of a rabies virus (rabv) vectored vaccine against ebola virus (ebov), a major threat to wild chimpanzees and gorillas. ebov gp and rabv gp-specific antibody titers increased exponentially during the trial, with rates of increase for six orally vaccinated chimpanzees very similar to four intramuscularly vaccinated controls. chimpanzee sera ...201728277549
one-health: a safe, efficient, dual-use vaccine for humans and animals against middle east respiratory syndrome coronavirus and rabies virus.middle east respiratory syndrome coronavirus (mers-cov) emerged in 2012 and is a highly pathogenic respiratory virus. there are no treatment options against mers-cov for humans or animals, and there are no large-scale clinical trials for therapies against mers-cov. to address this need, we developed an inactivated rabies virus (rabv) that contains the mers-cov spike (s) protein expressed on its surface. our initial recombinant vaccine, bnsp333-s, expresses a full-length wild-type mers-cov s prot ...201727807241
releasing the genomic rna sequestered in the mumps virus nucleocapsid.in a negative strand rna virus, the genomic rna is sequestered inside the nucleocapsid when the viral rna-dependent rna polymerase uses it as the template for viral rna synthesis. it must require a conformational change in the nucleocapsid protein (np) to make the rna accessible by the viral polymerase during this process. the structure of an empty mumps virus nucleocapsid-like particle is determined to 10.4 å resolution by cryoem image reconstruction. by modeling the crystal structure of parain ...201627581981
an inactivated rabies virus-based ebola vaccine, filorab1, adjuvanted with glucopyranosyl lipid a in stable emulsion confers complete protection in nonhuman primate challenge models.the 2013-2016 west african ebola virus (ebov) disease outbreak was the largest filovirus outbreak to date. over 28 000 suspected, probable, or confirmed cases have been reported, with a 53% case-fatality rate. the magnitude and international impact of this ebov outbreak has highlighted the urgent need for a safe and efficient ebov vaccine. to this end, we demonstrate the immunogenicity and protective efficacy of filorab1, a recombinant, bivalent, inactivated rabies virus-based ebov vaccine, in r ...201627456709
compounds derived from epigallocatechin-3-gallate (egcg) as a novel approach to the prevention of viral infections.pathogenic viral infections pose major health risks to humans and livestock due to viral infection-associated illnesses such as chronic or acute inflammation in crucial organs and systems, malignant and benign lesions. these lead to large number of illnesses and deaths worldwide each year. outbreaks of emerging lethal viruses, such as ebola virus, severe acute respiratory syndrome (sars) virus and middle east respiratory syndrome (mers) virus, could lead to epidemics or even pandemics if they ar ...201526490660
preclinical development of inactivated rabies virus-based polyvalent vaccine against rabies and filoviruses.we previously described the generation of a novel ebola virus (ebov) vaccine based on inactivated rabies virus (rabv) containing ebov glycoprotein (gp) incorporated in the rabv virion. our results demonstrated safety, immunogenicity, and protective efficacy in mice and nonhuman primates (nhps). protection against viral challenge depended largely on the quality of the humoral immune response against ebov gp.here we present the extension and improvement of this vaccine by increasing the amount of ...201526063224
lassa-vesicular stomatitis chimeric virus safely destroys brain tumors.high-grade tumors in the brain are among the deadliest of cancers. here, we took a promising oncolytic virus, vesicular stomatitis virus (vsv), and tested the hypothesis that the neurotoxicity associated with the virus could be eliminated without blocking its oncolytic potential in the brain by replacing the neurotropic vsv glycoprotein with the glycoprotein from one of five different viruses, including ebola virus, marburg virus, lymphocytic choriomeningitis virus (lcmv), rabies virus, and lass ...201525878115
controlled viral glycoprotein expression as a safety feature in a bivalent rabies-ebola vaccine.using a recombinant rabies (rabv) vaccine platform, we have developed several safe and effective vaccines. most recently, we have developed a rabv-based ebolavirus (ebov) vaccine that is efficacious in nonhuman primates. one safety feature of this vaccine is the utilization of a live but replication-deficient rabv construct. in this construct, the rabv glycoprotein (g) has been deleted from the genome, requiring g trans complementation in order for new infectious viruses to be released from the ...201525481284
human rabies deaths in africa: breaking the cycle of indifference.the current outbreak of ebola virus disease has mobilized the international community against this deadly disease. however, rabies, another deadly disease, is greatly affecting the african continent, with an estimated 25 000 deaths every year. and yet, the disease can be prevented by a vaccine, if necessary with immunoglobulin, even when administered after exposure to the rabies virus. rabies victims die because of neglect and ignorance, because they are not aware of these life-saving biological ...201525303941
plant-derived pharmaceuticals for the developing world.plant-produced vaccines and therapeutic agents offer enormous potential for providing relief to developing countries by reducing the incidence of infant mortality caused by infectious diseases. vaccines derived from plants have been demonstrated to effectively elicit an immune response. biopharmaceuticals produced in plants are inexpensive to produce, require fewer expensive purification steps, and can be stored at ambient temperatures for prolonged periods of time. as a result, plant-produced b ...201323857915
antibody quality and protection from lethal ebola virus challenge in nonhuman primates immunized with rabies virus based bivalent vaccine.we have previously described the generation of a novel ebola virus (ebov) vaccine platform based on (a) replication-competent rabies virus (rabv), (b) replication-deficient rabv, or (c) chemically inactivated rabv expressing ebov glycoprotein (gp). mouse studies demonstrated safety, immunogenicity, and protective efficacy of these live or inactivated rabv/ebov vaccines. here, we evaluated these vaccines in nonhuman primates. our results indicate that all three vaccines do induce potent immune re ...201323737747
a replication-deficient rabies virus vaccine expressing ebola virus glycoprotein is highly attenuated for neurovirulence.we are developing inactivated and live-attenuated rabies virus (rabv) vaccines expressing ebola virus (ebov) glycoprotein for use in humans and endangered wildlife, respectively. here, we further characterize the pathogenesis of the live-attenuated rabv/ebov vaccine candidates in mice in an effort to define their growth properties and potential for safety. rabv vaccines expressing gp (rv-gp) or a replication-deficient derivative with a deletion of the rabv g gene (rvδg-gp) are both avirulent aft ...201222889613
further characterization of the immune response in mice to inactivated and live rabies vaccines expressing ebola virus glycoprotein.we have previously developed (a) replication-competent, (b) replication-deficient, and (c) chemically inactivated rabies virus (rabv) vaccines expressing ebola virus (ebov) glycoprotein (gp) that induce humoral immunity against each virus and confer protection from both lethal rabv and mouse-adapted ebov challenge in mice. here, we expand our investigation of the immunogenic properties of these bivalent vaccines in mice. both live and killed vaccines induced primary ebov gp-specific t-cells and ...201222884661
a strategy to simultaneously eradicate the natural reservoirs of rabies and ebola virus.the efficacy of a recombinant live-attenuated or chemically inactivated bivalent vaccine against rabies virus (rabv) and ebola virus (ebov) infection was evaluated in a lethal mouse model of infection. the vaccines were derived from the live-attenuated street alabama dufferin b19 rabv platform already approved for veterinary use, where intramuscular, intranasal and intraperitoneal administration of the recombinant vaccines were avirulent in adult mice. significant levels of serum rabv- and ebov- ...201222309665
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