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the v domain of dog pvrl4 (nectin-4) mediates canine distemper virus entry and virus cell-to-cell spread.the entry of canine distemper virus (cdv) is a multistep process that involves the attachment of cdv hemagglutinin (h) to its cellular receptor, followed by fusion between virus and cell membranes. our laboratory recently identified pvrl4 (nectin-4) to be the epithelial receptor for measles and canine distemper viruses. in this study, we demonstrate that the v domain of pvrl4 is critical for cdv entry and virus cell-to-cell spread. furthermore, four key amino acid residues within the v domain of ...201424725937
morbillivirus vaccines: recent successes and future hopes.the impact of morbilliviruses on both human and animal populations is well documented in the history of mankind. indeed, prior to the development of vaccines for these diseases, morbilliviruses plagued both humans and their livestock that were heavily relied upon for food and motor power within communities. measles virus (mev) was responsible for the death of millions of people annually across the world and those fortunate enough to escape the disease often faced starvation where their livestock ...201424703852
genetic characterization of an isolate of canine distemper virus from a tibetan mastiff in china.canine distemper (cd) is a highly contagious, often fatal, multisystemic, and incurable disease in dogs and other carnivores, which is caused by canine distemper virus (cdv). although vaccines have been used as the principal means of controlling the disease, cd has been reported in vaccinated animals. the hemoagglutinin (h) protein is one of the most important antigens for inducing protective immunity against cd, and antigenic variation of recent cdv strains may explain vaccination failure. in t ...201424691820
domestic dog health worsens with socio-economic deprivation of their home communities.dogs play an important role in infectious disease transmission as reservoir hosts of many zoonotic and wildlife pathogens. nevertheless, unlike wildlife species involved in the life cycle of pathogens, whose health status might be a direct reflection of their fitness and competitive abilities, dog health condition could be sensitive to socio-economic factors impacting the well-being of their owners. here, we compare several dog health indicators in three rural communities of panama with differen ...201424681221
molecular typing of canine distemper virus strains reveals the presence of a new genetic variant in south america.canine distemper virus (cdv, paramyxoviridae, morbillivirus) is the causative agent of a severe infectious disease affecting terrestrial and marine carnivores worldwide. phylogenetic relationships and the genetic variability of the hemagglutinin (h) protein and the fusion protein signal-peptide (fsp) allow for the classification of field strains into genetic lineages. currently, there are nine cdv lineages worldwide, two of them co-circulating in south america. using the fsp-coding region, we an ...201424647552
whole genome sequence analysis of the arctic-lineage strain responsible for distemper in italian wolves and dogs through a fast and robust next generation sequencing protocol.dynamic surveillance and characterization of canine distemper virus (cdv) circulating strains are essential against possible vaccine breakthroughs events. this study describes the setup of a fast and robust next-generation sequencing (ngs) ion pgm™ protocol that was used to obtain the complete genome sequence of a cdv isolate (cdv2784/2013). cdv2784/2013 is the prototype of cdv strains responsible for severe clinical distemper in dogs and wolves in italy during 2013. cdv2784/2013 was isolated on ...201424642239
emergence of canine distemper virus strains with two amino acid substitutions in the haemagglutinin protein, detected from vaccinated carnivores in north-eastern china in 2012-2013.a total of 16 strains of canine distemper virus (cdv) were detected from vaccinated minks, foxes, and raccoon dogs in four provinces in north-eastern china between the end of 2011 and 2013. upon sequence analysis of the haemagglutinin gene and comparison with wild-type cdv from different species in the same geographical areas, two non-synonymous single nucleotide polymorphisms were identified in 10 cdv strains, which led to amino acid changes at positions 542 (isoleucine to asparagine) and 549 ( ...201424618397
invasive american mink: linking pathogen risk between domestic and endangered carnivores.infectious diseases, in particular canine distemper virus (cdv), are an important threat to the viability of wild carnivore populations. cdv is thought to be transmitted by direct contact between individuals; therefore, the study of species interactions plays a pivotal role in understanding cdv transmission dynamics. however, cdv often appears to move between populations that are ecologically isolated, possibly through bridge hosts that interact with both species. this study investigated how an ...201424604545
canine distemper virus and badgers. 201424578436
a monoclonal antibody against truncated n protein (aa 277-471) of canine distemper virus.canine distemper (cd) is a highly contagious, systemic, viral disease of dogs seen worldwide. the nucleocapsid protein (np) of canine distemper virus encloses virus assembly and has some regulatory functions in viral transcription and replication. here, we describe a procedure to generate a monoclonal antibody (mab) against cdv n protein and investigate its characteristics. western blot analysis showed that the mabs produced in this study were against cdv n specifically. indirect immunofluoresce ...201424555938
real-time reverse transcription polymerase chain reaction method for detection of canine distemper virus modified live vaccine shedding for differentiation from infection with wild-type strains.canine distemper virus (cdv) remains a common cause of infectious disease in dogs, particularly in high-density housing situations such as shelters. vaccination of all dogs against cdv is recommended at the time of admission to animal shelters and many use a modified live virus (mlv) vaccine. from a diagnostic standpoint for dogs with suspected cdv infection, this is problematic because highly sensitive diagnostic real-time reverse transcription polymerase chain reaction (rt-pcr) tests are able ...201424532693
using the ferret model to study morbillivirus entry, spread, transmission and cross-species infection.canine distemper virus (cdv) is an animal morbillivirus with a worldwide circulation that infects carnivores, including domestic dogs and an assortment of wildlife hosts. the development of reverse genetics systems for wild-type strains of cdv and the use of the resulting recombinant (r) viruses to infect ferrets by a natural route has shed new light on the temporal pathogenesis of distemper. combining fluorescent protein expressing recombinant viruses and multimodal, macroscopic and microscopic ...201424525290
first report of clinical disease associated with canine distemper virus infection in a wild black bear (ursus americana).an approximately 1-yr-old black bear was discovered on the porch of a rural residence in southwestern pennsylvania on october 26, 2011, where it remained during the day in spite of efforts to frighten it away. the bear exhibited periods of somnolence and sporadic tremors and seizures. it was euthanized by gunshot that evening. immediately after euthanasia it was observed to have footpads that exuded fluid when compressed. it was submitted for necropsy the next day where roughened footpads were n ...201324502734
pathogen exposure and blood chemistry in the washington, usa population of northern sea otters (enhydra lutris kenyoni).northern sea otters (enhydra lutris kenyoni) from washington state, united states were evaluated in 2011 to determine health status and pathogen exposure. antibodies to brucella spp. (10%) and influenza a virus (23%) were detected for the first time in this population in 2011. changes in clinical pathology values (serum chemistries), exposure to pathogens, and overall health of the population over the last decade were assessed by comparing 2011 data to the data collected on this population in 20 ...201324502716
measles vaccination of nonhuman primates provides partial protection against infection with canine distemper virus.measles virus (mv) is being considered for global eradication, which would likely reduce compliance with mv vaccination. as a result, children will grow up without mv-specific immunity, creating a potential niche for closely related animal morbilliviruses such as canine distemper virus (cdv). natural cdv infection causing clinical signs has never been reported in humans, but recent outbreaks in captive macaques have shown that cdv can cause disease in primates. we studied the virulence and tropi ...201424501402
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
arctic lineage-canine distemper virus as a cause of death in apennine wolves (canis lupus) in italy.canine distemper virus (cdv) infection is a primary threat affecting a wide number of carnivore species, including wild animals. in january 2013, two carcasses of apennine wolves (canis lupus) were collected in ortona dei marsi (l'aquila province, italy) by the local veterinary services. cdv was immediately identified either by rt-pcr or immunohistochemistry in lung and central nervous tissue samples. at the same time, severe clinical signs consistent with cdv infection were identified and taped ...201424465373
wildlife reservoirs of canine distemper virus resulted in a major outbreak in danish farmed mink (neovison vison).a major outbreak of canine distemper virus (cdv) in danish farmed mink (neovison vison) started in the late summer period of 2012. at the same time, a high number of diseased and dead wildlife species such as foxes, raccoon dogs, and ferrets were observed. to track the origin of the outbreak virus full-length sequencing of the receptor binding surface protein hemagglutinin (h) was performed on 26 cdv's collected from mink and 10 cdv's collected from wildlife species. subsequent phylogenetic anal ...201424454897
comparison of oral and intramuscular recombinant canine distemper vaccination in african wild dogs (lycaon pictus).a series of three doses of recombinant canary-pox-vectored canine distemper virus vaccine was administered at 1-mo intervals, orally (n = 8) or intramuscularly (n = 13), to 21 previously unvaccinated juvenile african wild dogs (lycaon pictus) at the wildlife conservation society's bronx zoo. titers were measured by serum neutralization at each vaccination and at intervals over a period of 3.5-21.5 mo after the initial vaccination. all postvaccination titers were negative for orally vaccinated an ...201324450046
morbillivirus control of the interferon response: relevance of stat2 and mda5 but not stat1 for canine distemper virus virulence in ferrets.the v proteins of paramyxoviruses control the innate immune response. in particular, the v protein of the genus morbillivirus interferes with the signal transducer and activator of transcription 1 (stat1), stat2, and melanoma differentiation-associated protein 5 (mda5) signaling pathways. to characterize the contributions of these pathways to canine distemper virus (cdv) pathogenesis, we took advantage of the knowledge about the mechanisms of interaction between the measles virus v protein with ...201424371065
molecular determinants defining the triggering range of prefusion f complexes of canine distemper virus.the morbillivirus cell entry machinery consists of a fusion (f) protein trimer that refolds to mediate membrane fusion following receptor-induced conformational changes in its binding partner, the tetrameric attachment (h) protein. to identify molecular determinants that control f refolding, we generated f chimeras between measles virus (mev) and canine distemper virus (cdv). we located a central pocket in the globular head domain of cdv f that regulates the stability of the metastable, prefusio ...201424371057
genotyping of canine distemper virus strains circulating in brazil from 2008 to 2012.canine distemper virus (cdv) is a major pathogen of dogs and represents a serious threat to both unvaccinated and vaccinated animals. this study surveyed dogs with or without clinical signs related to canine distemper from different regions of brazil from 2008 to 2012. a total of 155 out of 386 animals were found to be cdv positive by rt-pcr; 37 (23.8%) dogs were asymptomatic at the time of sampling, and 90 (58%) displayed clinical signs suggestive of distemper. nineteen (12.2%) dogs had a recor ...201424370870
the v protein of canine distemper virus is required for virus replication in human epithelial cells.canine distemper virus (cdv) becomes able to use human receptors through a single amino acid substitution in the h protein. in addition, cdv strains possessing an intact c protein replicate well in human epithelial h358 cells. the present study showed that cdv strain 007lm, which was isolated from lymph node tissue of a dog with distemper, failed to replicate in h358 cells, although it possessed an intact c protein. sequence analyses suggested that a cysteine-to-tyrosine substitution at position ...201324358174
common and emerging infectious diseases in the animal shelter.the beneficial role that animal shelters play is unquestionable. an estimated 3 to 4 million animals are cared for or placed in homes each year, and most shelters promote public health and support responsible pet ownership. it is, nonetheless, inevitable that shelters are prime examples of anthropogenic biological instability: even well-run shelters often house transient, displaced, and mixed populations of animals. many of these animals have received minimal to no prior health care, and some ha ...201424265288
dynamic changes of foxp3(+) regulatory t cells in spleen and brain of canine distemper virus-infected dogs.canine distemper virus (cdv) infection causes immunosuppression and demyelinating leukoencephalitis in dogs. in viral diseases, an ambiguous function of regulatory t cells (treg), with both beneficial effects by reducing immunopathology and detrimental effects by inhibiting antiviral immunity, has been described. however, the role of treg in the pathogenesis of canine distemper remains unknown. in order to determine the effect of cdv upon immune homeostasis, the amount of foxp3(+) treg in spleen ...201324210687
sandwich-dot enzyme-linked immunosorbent assay for the detection of canine distemper virus.a sandwich-dot enzyme-linked immunosorbent assay (dot elisa) was developed for the detection of canine distemper virus (cdv). in 56 dogs suspected to have cd the rates of detection of cdv antigen in samples of blood lymphocytes and palpebral conjunctiva by dot elisa and elisa were, respectively, 91% (49/54) and 81% (44/54) for the lymphocyte samples and 88% (28/32) and 75% (24/32) for the conjunctival samples. the cdv detection limits were 10 ng/50 μl for dot elisa and 40 ng/50 μl for elisa. the ...201324124274
canine distemper virus antibody test alone increases misdiagnosis of distemper encephalitis. 201324106247
membrane-bound siv envelope trimers are immunogenic in ferrets after intranasal vaccination with a replication-competent canine distemper virus vector.we are investigating canine distemper virus (cdv) as a vaccine vector for the delivery of hiv envelope (env) that closely resembles the native trimeric spike. we selected cdv because it will promote vaccine delivery to lymphoid tissues, and because human exposure is infrequent, reducing potential effects of pre-existing immunity. using siv env as a model, we tested a number of vector and gene insert designs. vectors containing a gene inserted between the cdv h and l genes, which encoded env lack ...201324074564
canine distemper virus (cdv) in another big cat: should cdv be renamed carnivore distemper virus?one of the greatest threats to the conservation of wild cat populations may be dogs or, at least, one of their viruses. canine distemper virus (cdv), a single-stranded rna virus in the paramyxoviridae family and genus morbillivirus, infects and causes disease in a variety of species, not just canids. an outbreak of cdv in wild lions in the serengeti, tanzania, in 1994 was a wake-up call for conservationists, as it demonstrated that an infectious disease could swiftly impact a previously healthy ...201324045642
canine distemper virus: an emerging disease in wild endangered amur tigers (panthera tigris altaica).fewer than 500 amur tigers (panthera tigris altaica) remain in the wild. due to low numbers and their solitary and reclusive nature, tiger sightings across their range in the russian far east and china are rare; sightings of sick tigers are rarer still. serious neurologic disease observed in several wild tigers since 2001 suggested disease emergence in this endangered species. to investigate this possibility, histology, immunohistochemistry (ihc), in situ hybridization (ish), and reverse transcr ...201323943758
detection and differentiation of field and vaccine strains of canine distemper virus using reverse transcription followed by nested real time pcr (rt-nqpcr) and rflp analysis.canine distemper virus (cdv) is the cause of a severe and highly contagious disease in dogs. practical diagnosis of canine distemper based on clinical signs and laboratory tests are required to confirm cdv infection. the present study aimed to develop a molecular assay to detect and differentiate field and vaccine cdv strains. reverse transcription followed by nested real time polymerase chain reaction (rt-nqpcr) was developed, which exhibited analytical specificity (all the samples from healthy ...201323942341
cutaneous lesions associated with dual infection caused by canine distemper virus and orthopoxvirus in a domestic cat.within the context of an increased epidemiological pressure caused by canine distemper virus (cdv) in switzerland together with a potential re-emergence of endemic pathogens such as orthopoxviruses (opxv), dual infections are possible among susceptible species.201323869471
complete nucleotide sequence of porcine circovirus 2 isolated from piglets in china.a new strain of canine distemper virus, strain hx, has been isolated from piglets in china, and its complete genome has been sequenced and analyzed. phylogenetic analysis suggests that hx belongs to the 2d genotype cluster and it is highly prevalent in china.201323868119
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
genotypic lineages and restriction fragment length polymorphism of canine distemper virus isolates in thailand.canine distemper virus (cdv) is known to cause multisystemic disease in all families of terrestrial carnivores. attenuated live vaccines have been used to control cdv in a variety of species for many decades, yet a number of cdv infections in vaccinated dogs are still observed. the aims of this study were to investigate the genetic diversity of cdv lineages based on phosphoprotein (p), hemagglutinin (h) and fusion protein (f) genes and to develop the restriction fragment length polymorphism (rfl ...201323830775
duration of maternal antibodies against canine distemper virus and hendra virus in pteropid bats.old world frugivorous bats have been identified as natural hosts for emerging zoonotic viruses of significant public health concern, including henipaviruses (nipah and hendra virus), ebola virus, and marburg virus. epidemiological studies of these viruses in bats often utilize serology to describe viral dynamics, with particular attention paid to juveniles, whose birth increases the overall susceptibility of the population to a viral outbreak once maternal immunity wanes. however, little is unde ...201323826322
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
serologic response of harbor seals (phoca vitulina) to vaccination with a recombinant canine distemper vaccine.morbilliviruses pose a significant threat to marine mammal populations around the world and have been associated with multiple epizootics in pinnipeds and cetaceans. as part of a preventive veterinary medical program, five harbor seals (phoca vitulina) in a managed collection were vaccinated with a recombinant canarypox-vectored canine distemper virus vaccine. the vaccine was evaluated for safety (by monitoring seals for local and systemic adverse effects and by testing for shedding of the canar ...201323778607
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
paramyxovirus infections in ex vivo lung slice cultures of different host species.paramyxoviruses, including measles virus (mv), human metapneumovirus (hmpv), human respiratory syncytial virus (hrsv) and canine distemper virus (cdv), are transmitted via the respiratory route. despite their close phylogenetic relationship, the pathogenesis of these viruses is very different. to study viral tropism and replication ex vivo, a protocol for the inflation of lungs with low-melting-point agarose mixed with culture medium was established. lung slices were prepared and remained viable ...201323777750
supplementation of diets with bovine colostrum influences immune function in dogs.while the need for colostrum in neonates is well established, the systemic effect of feeding bovine colostrum (bc) to adult humans is gaining increasing attention. however, no systematic studies evaluating the immunomodulatory effect of bc in dogs have been reported. the aim of the present study was to evaluate the immunomodulatory effect of dietary supplementation of bc in dogs. the study was conducted in two phases: pre-test (8 weeks) and test (40 weeks), with twenty-four dogs (mean age 2.5 ye ...201323773360
complete nucleotide sequence of canine distemper virus cdv-ps, isolated from dogs in china.a new strain of canine distemper virus, cdv-ps, has been isolated from dogs in china, and its complete genome has been sequenced and analyzed. the phylogenetic analysis suggests that cdv-ps belongs to the asia-1 cluster and has low identity to the vaccine strain.201323682141
the fusion protein signal-peptide-coding region of canine distemper virus: a useful tool for phylogenetic reconstruction and lineage identification.canine distemper virus (cdv; paramyxoviridae, morbillivirus) is the etiologic agent of a multisystemic infectious disease affecting all terrestrial carnivore families with high incidence and mortality in domestic dogs. sequence analysis of the hemagglutinin (h) gene has been widely employed to characterize field strains, permitting the identification of nine cdv lineages worldwide. recently, it has been established that the sequences of the fusion protein signal-peptide (fsp) coding region are e ...201323675493
assessing demographic and epidemiologic parameters of rural dog populations in india during mass vaccination campaigns.mass vaccination of dogs is a mainstay for efforts to control rabies and other viral pathogens. the success of such programs is a function of the ability to vaccinate sufficient proportions of animals to develop herd immunity. however, fully assessing success in reaching target vaccination-levels and in understanding the outcome of mass vaccination efforts is hindered if insufficient information is available on the demographics of dog populations and the prevalence of the targeted pathogens. whi ...201323664490
in vitro inhibition of canine distemper virus by flavonoids and phenolic acids: implications of structural differences for antiviral design.infection caused by canine distemper virus (cdv) is a highly contagious disease with high incidence and lethality in the canine population. antiviral activity of flavonoids quercetin, morin, rutin and hesperidin, and phenolic cinnamic, trans-cinnamic and ferulic acids were evaluated in vitro against the cdv using the time of addition assay to determine which step of the viral replicative cycle was affected. all flavonoids displayed great viral inhibition when they were added at the times 0 (adso ...201323664014
[entry mechanism of morbillivirus family].the genus morbillivirus includes measles virus, canine distemper virus and rinderpest virus. these are highly contagious and exhibit high mortality. these viruses have the attachment glycoprotein, hemagglutinin (h), at the virus surface, which bind to signaling lymphocyte activation molecule (slam) and nectin 4 as receptors for the entry. however, the molecular mechanism for this entry has been limitedly understood. here we summarize the current topics, (1) newly identified receptor, nectin 4, ( ...201323649396
zymographic patterns of mmp-2 and mmp-9 in the csf and cerebellum of dogs with subacute distemper leukoencephalitis.distemper leukoencephalitis is a disease caused by the canine distemper virus (cdv) infection. it is a demyelinating disease affecting mainly the white matter of the cerebellum and areas adjacent to the fourth ventricle; the enzymes of the matrix metalloproteinases (mmps) group, especially mmp-2 and mmp-9 have a key role in the myelin basic protein fragmentation and in demyelination, as well as in leukocyte traffic into the nervous milieu. to evaluate the involvement of mmps during subacute dist ...201323639293
rabies and canine distemper virus epidemics in the red fox population of northern italy (2006-2010).since 2006 the red fox (vulpes vulpes) population in north-eastern italy has experienced an epidemic of canine distemper virus (cdv). additionally, in 2008, after a thirteen-year absence from italy, fox rabies was re-introduced in the udine province at the national border with slovenia. disease intervention strategies are being developed and implemented to control rabies in this area and minimise risk to human health. here we present empirical data and the epidemiological picture relating to the ...201323630599
deduced sequences of the membrane fusion and attachment proteins of canine distemper viruses isolated from dogs and wild animals in korea.canine distemper virus (cdv) causes highly contagious respiratory, gastrointestinal, and neurological diseases in wild and domestic animal species. despite a broad vaccination campaign, the disease is still a serious problem worldwide. in this study, six field cdv strains were isolated from three dogs, two raccoon dogs, and one badger in korea. the full sequence of the genes encoding fusion (f) and hemagglutinin (h) proteins were compared with those of other cdvs including field and vaccine stra ...201323624803
canine distemper virus associated with a lethal outbreak in monkeys can readily adapt to use human receptors.a canine distemper virus (cdv) strain, cyn07-dv, associated with a lethal outbreak in monkeys, used human signaling lymphocyte activation molecule as a receptor only poorly but readily adapted to use it following a p541s substitution in the hemagglutinin protein. since cyn07-dv had an intrinsic ability to use human nectin-4, the adapted virus became able to use both human immune and epithelial cell receptors, as well as monkey and canine ones, suggesting that cdv can potentially infect humans.201323596291
risk factors for exposure to feline pathogens in california mountain lions (puma concolor).the primary challenge to mountain lion population viability in california is habitat loss and fragmentation. these habitat impacts could enhance disease risk by increasing contact with domestic animals and by altering patterns of exposure to other wild felids. we performed a serologic survey for feline pathogens in california mountain lions (puma concolor) using 490 samples from 45 counties collected from 1990 to 2008. most mountain lions sampled were killed because of depredation or public safe ...201323568903
phylogenetic analysis of the haemagglutinin gene of canine distemper virus strains detected from giant panda and raccoon dogs in china.canine distemper virus (cdv) infects a variety of carnivores, including wild and domestic canidae. in this study, we sequenced and phylogenetic analyses of the hemagglutinin (h) genes from eight canine distemper virus (cdv) isolates obtained from seven raccoon dogs (nyctereutes procyonoides) and a giant panda (ailuropoda melanoleuca) in china.201323566727
experimental adaptation of wild-type canine distemper virus (cdv) to the human entry receptor cd150.canine distemper virus (cdv), a close relative of measles virus (mv), is widespread and well known for its broad host range. when the goal of measles eradication may be achieved, and when measles vaccination will be stopped, cdv might eventually cross the species barrier to humans and emerge as a new human pathogen. in order to get an impression how fast such alterations may occur, we characterized required adaptive mutations to the human entry receptors cd150 (slam) and nectin-4 as first step t ...201323554862
phylogenetic analyses of the hemagglutinin gene of wild-type strains of canine distemper virus in southern brazil.this study examined the phylogenetic relationship of strains of canine distemper virus (cdv) collected from paraná state, brazil, based on the hemagglutinin gene. urine samples were collected from 4 dogs from northern paraná state that demonstrated clinical manifestations of canine distemper. the participation of cdv was initially confirmed by rt-pcr targeting the nucleocapsid protein, after which the complete hemagglutinin gene was sequenced from each sample. sequences were deposited in and com ...201323546971
function of feline signaling lymphocyte activation molecule as a receptor of canine distemper virus.morbilliviruses use signaling lymphocyte activation molecule (slam) as a receptor for their entry to cells. in this study, a complete gene encoding slam of a domestic cat was identified. the identity of feline slam with canine one was 73%, and feline slam formed the same cluster with those of carnivores. furthermore, feline cell expressing feline slam supported growth of canine distemper virus (cdv) as well as that expressing canine one. these results indicated that feline slam can function as a ...201323535266
detection of canine distemper virus serum neutralizing antibodies in captive u.s. phocids.antibodies to morbilliviruses have been documented in free-ranging pinnipeds throughout populations in the atlantic and arctic oceans, but not from the pacific ocean. as a symbolic geographic barrier between the exposed atlantic and naive pacific populations, the captive phocid population in north america had undocumented serologic status. in this study, canine distemper virus (cdv) serum neutralization assays were used to assess the prevalence of antibodies in this population with participation ...201323505705
leukocyte adhesion deficiency type i in a mixed-breed dog.a 6-month-old, neutered male, mixed-breed dog was examined for a 2-month persistent fever, nonhealing dermal metacarpal area wound, and leukocytosis (47.0-198.0 × 10(3)/μl). serum chemistry findings included hypoalbuminemia, hyperglobulinemia, hyperphosphatemia, and hyperphosphatasemia. complete blood cell count results revealed a moderate microcytic, hypochromic nonregenerative anemia with a profound leukocytosis (198.5 × 10(3)/μl), characterized by neutrophilia with toxicity and hypersegmentat ...201323417082
complete nucleotide sequence of canine distemper virus hlj1-06, isolated from foxes in china.a new strain of canine distemper virus, hlj1-06, has been isolated from foxes in china, and its complete genome has been sequenced and analyzed. the phylogenetic analysis suggests that hlj1-06 belongs to the asia-1 cluster and has low identity to the vaccine strain.201323405331
fatal combined infection with canine distemper virus and orthopoxvirus in a group of asian marmots (marmota caudata).a fatal combined infection with canine distemper virus (cdv) and orthopoxvirus (opxv) in asian marmots (marmota caudata) is reported in this article. a total of 7 asian marmots from a small zoological garden in switzerland were found dead in hibernation during a routine check in the winter of 2011. the marmots died in february 2011. no clinical signs of disease were observed at any time. the viruses were detected in all individuals for which the tissues were available (n = 3). detection of the v ...201323381928
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
concomitant canine distemper, infectious canine hepatitis, canine parvoviral enteritis, canine infectious tracheobronchitis, and toxoplasmosis in a puppy.the concomitant infections of canine distemper virus (cdv), canine adenovirus a types 1 (cadv-1) and 2 (cadv-2), canine parvovirus type 2 (cpv-2), and toxoplasma gondii are described in a 43-day-old mixed-breed puppy. clinically, there were convulsions and blindness with spontaneous death; 14 siblings of this puppy, born to a 10-month-old dam, which was seropositive (titer: 1,024) for t. gondii, also died. necropsy revealed unilateral corneal edema (blue eye), depletion of intestinal lymphoid ti ...201323293164
characteristics of a canine distemper virus outbreak in dichato, chile following the february 2010 earthquake.following the earthquake and tsunami disaster in chile in february 2010, residents of dichato reported high morbidity and mortality in dogs, descriptions of which resembled canine distemper virus (cdv). to assess the situation, free vaccine clinics were offered in april and may. owner information, dog history and signalment were gathered; dogs received physical examinations and vaccines protecting against cdv, and other common canine pathogens. blood was collected to screen for igm antibodies to ...201326479537
dog nectin-4 is an epithelial cell receptor for canine distemper virus that facilitates virus entry and syncytia formation.canine distemper virus (cdv) was shown to use dog nectin-4 as a receptor to gain entry into epithelial cells. rna from dog placenta or mdck kidney cells was isolated and cdnas were prepared. two splice variants of dog nectin-4 were identified. a deletion of 25 amino acids was found in the cytoplasmic domain of dog nectin-4 from mdck cells, corresponding to a splice variant that is also seen in murine nectin-4, and did not affect its role as a receptor. both dog nectin-4 and human nectin-4 could ...201323260107
antagonistic pleiotropy and fitness trade-offs reveal specialist and generalist traits in strains of canine distemper virus.theoretically, homogeneous environments favor the evolution of specialists whereas heterogeneous environments favor generalists. canine distemper is a multi-host carnivore disease caused by canine distemper virus (cdv). the described cell receptor of cdv is slam (cd150). attachment of cdv hemagglutinin protein (cdv-h) to this receptor facilitates fusion and virus entry in cooperation with the fusion protein (cdv-f). we investigated whether cdv strains co-evolved in the large, homogeneous domesti ...201223239996
immunopathogenic and neurological mechanisms of canine distemper virus.canine distemper is a highly contagious viral disease caused by the canine distemper virus (cdv), which is a member of the morbillivirus genus, paramyxoviridae family. animals that most commonly suffer from this disease belong to the canidae family; however, the spectrum of natural hosts for cdv also includes several other families of the order carnivora. the infectious disease presents worldwide distribution and maintains a high incidence and high levels of lethality, despite the availability o ...201223193403
duration of serological response to canine parvovirus-type 2, canine distemper virus, canine adenovirus type 1 and canine parainfluenza virus in client-owned dogs in australia.to determine whether client-owned dogs in australia, last vaccinated with canvac(®) vaccines containing canine parvovirus-type 2 (cpv-2), canine distemper virus (cdv), canine adenovirus type 2 (cav-2) ± canine parainfluenza virus (cpiv) at least 18 months ago, were seropositive or responded serologically to revaccination.201223186088
canine distemper virus with the intact c protein has the potential to replicate in human epithelial cells by using human nectin4 as a receptor.recent outbreaks in monkeys have proven that canine distemper virus (cdv) causes diseases in a wide range of mammals. cdv uses slam and nectin4 as receptors to replicate in susceptible animals. here, we show that human nectin4, but not human slam, is fully functional as a cdv receptor. the cdv ac96i strain hardly replicated in nectin4-expressing human epithelial nci-h358 cells, but readily adapted to grow in them. unsurprisingly, no amino acid change in the h protein was required for the adaptat ...201323174504
lethal canine distemper virus outbreak in cynomolgus monkeys in japan in 2008.canine distemper virus (cdv) has recently expanded its host range to nonhuman primates. a large cdv outbreak occurred in rhesus monkeys at a breeding farm in guangxi province, china, in 2006, followed by another outbreak in rhesus monkeys at an animal center in beijing in 2008. in 2008 in japan, a cdv outbreak also occurred in cynomolgus monkeys imported from china. in that outbreak, 46 monkeys died from severe pneumonia during a quarantine period. a cdv strain (cyn07-dv) was isolated in vero ce ...201323135729
canine distemper in an isolated population of fishers (martes pennanti) from california.four fishers (martes pennanti) from an insular population in the southern sierra nevada mountains, california, usa died as a consequence of an infection with canine distemper virus (cdv) in 2009. three fishers were found in close temporal and spatial relationship; the fourth fisher died 4 mo later at a 70 km distance from the initial group. gross lesions were restricted to hyperkeratosis of periocular skin and ulceration of footpads. all animals had necrotizing bronchitis and bronchiolitis with ...201223060505
canine distemper outbreak in pet store puppies linked to a high-volume dog breeder.canine distemper is uncommon in the pet trade in the united states, in large part due to effective vaccines against canine distemper virus (cdv). this is a report of cdv affecting 24 young dogs of multiple breeds shortly after sale by 2 pet stores in wyoming during august-october 2010. cases were diagnosed over 37 days. diagnosis was established by a combination of fluorescent antibody staining, reverse transcription polymerase chain reaction, negative stain electron microscopy, and necropsy wit ...201223012378
occurrence and geographical distribution of canine distemper virus infection in red foxes (vulpes vulpes) of saxony-anhalt, germany.canine distemper virus (cdv) infects dogs and a variety of carnivore species. in saxony-anhalt, a federal state of germany, 761 foxes were examined for cdv infection, using real-time polymerase chain reaction (pcr), in the years 2010 and 2011. a prevalence of 30.5% was found for the whole time period without significant changes in prevalence between 2010 and 2011. the relative risk (rr) of a fox to test positive for cdv varied markedly within the area of the state and was significantly increased ...201322999912
simultaneous detection of canine respiratory disease associated viruses by a multiplex reverse transcription-polymerase chain reaction assay.a multiplex reverse transcription polymerase chain reaction (mrt-pcr) assay was developed for the simultaneous detection of canine distemper virus (cdv), canine respiratory coronavirus (crcov) and canine influenza virus (civ). these viral pathogens are all causative agents of canine infectious respiratory disease (cird). the sensitivity and specificity of the mrt-pcr were determined by comparing it to a rapid antigen test (rat) or immuno-chromatography test kit and reverse transcription-polymera ...201322971595
canine cd4+cd8+ double positive t cells in peripheral blood have features of activated t cells.in dogs a cd4(+)cd8(+) double positive t cell subpopulation exists that has not been phenotypically defined yet. we demonstrate that canine cd4(+)cd8(+) t cells are mature cd1a(-) and tcrαβ(+) t cells. to analyse the activation potential of cd4(+)cd8(+) t cells, pbmc from dogs vaccinated against canine distemper virus (cdv) were re-stimulated with cdv. upon antigen-specific stimulation, the cd4(+)cd8(+) t cell fraction increases and consists nearly exclusively of proliferated cells. similarly, o ...201222789871
nectin4 is an epithelial cell receptor for canine distemper virus and involved in neurovirulence.canine distemper virus (cdv) uses signaling lymphocyte activation molecule (slam), expressed on immune cells, as a receptor. however, epithelial and neural cells are also affected by cdv in vivo. wild-type cdv strains showed efficient replication with syncytia in vero cells expressing dog nectin4, and the infection was blocked by an anti-nectin4 antibody. in dogs with distemper, cdv antigen was preferentially detected in nectin4-positive neurons and epithelial cells, suggesting that nectin4 is a ...201222761370
dna vaccines encoding proteins from wild-type and attenuated canine distemper virus protect equally well against wild-type virus challenge.immunity induced by dna vaccines containing the hemagglutinin (h) and nucleoprotein (n) genes of wild-type and attenuated canine distemper virus (cdv) was investigated in mink (mustela vison), a highly susceptible natural host of cdv. all dna-immunized mink seroconverted, and significant levels of virus-neutralizing (vn) antibodies were present on the day of challenge with wild-type cdv. the dna vaccines also primed the cell-mediated memory responses, as indicated by an early increase in the num ...201222714870
peste des petits ruminants virus detected in tissues from an asiatic lion (panthera leo persica) belongs to asian lineage iv.in this study, peste des petits ruminants virus (pprv) was detected in frozen pooled tissue samples from a dead asiatic lion (panthera leo persica). the samples were negative for canine distemper virus and positive for pprv nucleic acids when tested with one-step rt-pcr using the appropriate virus-specific primers. subsequent amplification, cloning, and sequencing of the partial nucleocapsid, matrix, and fusion genes confirmed the presence of pprv nucleic acid. comparative sequence and phylogene ...201222705744
evaluation of synthetic infection-enhancing lipopeptides as adjuvants for a live-attenuated canine distemper virus vaccine administered intra-nasally to ferrets.inactivated paramyxovirus vaccines have been associated with hypersensitivity responses upon challenge infection. for measles and canine distemper virus (cdv) safe and effective live-attenuated virus vaccines are available, but for human respiratory syncytial virus and human metapneumovirus development of such vaccines has proven difficult. we recently identified three synthetic bacterial lipopeptides that enhance paramyxovirus infections in vitro, and hypothesized these could be used as adjuvan ...201222705079
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
booster effect of canine distemper, canine parvovirus infection and infectious canine hepatitis combination vaccine in domesticated adult dogs.domesticated adult dogs with antibody titer classified as below 'high' to one or more of canine distemper virus (cdv), canine parvovirus type-2 (cpv-2) and canine adenovirus type-1 (cadv-1) were then given an additional inoculation, and the effectiveness of this booster evaluated 2 months later. consequently, cdv and cadv-1 antibody titer experienced a significant increase, but the same effect was not observed in the antibody titer of cpv-2. these findings suggest that with additional inoculatio ...201222672137
epidemiology of canine distemper virus in wild raccoon dogs (nyctereutes procyonoides) from south korea.raccoon dogs (nyctereutes procyonoides) are widespread and common in south korea. in 2011, we obtained serum samples from 102 wild raccoon dogs to survey their exposure to canine distemper virus (cdv). forty-five of the 102 animals (44.1%) were seropositive. field cases of canine distemper in wild raccoon dogs from 2010 to 2011 were investigated. fourteen cases of cdv infection were identified by a commercially available cdv antigen detection kit. these cases were used for virus isolation and mo ...201222608695
recombinant canine distemper virus strain snyder hill expressing green or red fluorescent proteins causes meningoencephalitis in the ferret.the propensity of canine distemper virus (cdv) to spread to the central nervous system is one of the primary features of distemper. therefore, we developed a reverse genetics system based on the neurovirulent snyder hill (sh) strain of cdv (cdv(sh)) and show that this virus rapidly circumvents the blood-brain and blood-cerebrospinal fluid (csf) barriers to spread into the subarachnoid space to induce dramatic viral meningoencephalitis. the use of recombinant cdv(sh) (rcdv(sh)) expressing enhance ...201222553334
bats host major mammalian paramyxoviruses.the large virus family paramyxoviridae includes some of the most significant human and livestock viruses, such as measles-, distemper-, mumps-, parainfluenza-, newcastle disease-, respiratory syncytial virus and metapneumoviruses. here we identify an estimated 66 new paramyxoviruses in a worldwide sample of 119 bat and rodent species (9,278 individuals). major discoveries include evidence of an origin of hendra- and nipah virus in africa, identification of a bat virus conspecific with the human ...201222531181
comparison of two assays for detection of antibodies against canine parvovirus and canine distemper virus in dogs admitted to a florida animal shelter.to compare 2 assays for use in the identification of dogs with a protective antibody titer (pat) against canine parvovirus (cpv) and canine distemper virus (cdv).201222515628
virological survey in free-ranging wildcats (felis silvestris) and feral domestic cats in portugal.to determine the presence of viral pathogens in natural areas a survey was conducted on an opportunistic sample of fifty eight wild (felis silvestris silvestris) and feral cats (f. s. catus). the biological materials included serum, lung tissue extract and stool. feline leukemia virus p27 antigen was detected in 13/50 serum/lung tissue extract samples (26%), canine distemper virus antibodies were detected in 2/26 serum/lung tissue extract samples (7.7%), feline coronavirus rna was present in 6/2 ...201222424865
morbillivirus glycoprotein expression induces er stress, alters ca2+ homeostasis and results in the release of vasostatin.although the pathology of morbillivirus in the central nervous system (cns) is well described, the molecular basis of neurodegenerative events still remains poorly understood. as a model to explore morbillivirus-mediated cns dysfunctions, we used canine distemper virus (cdv) that we inoculated into two different cell systems: a monkey cell line (vero) and rat primary hippocampal neurons. importantly, the recombinant cdv used in these studies not only efficiently infects both cell types but recap ...201222403712
morbillivirus receptors and tropism: multiple pathways for infection.morbilliviruses, which include measles virus (mev), canine distemper virus, and rinderpest virus, are among the most important pathogens in their respective hosts and cause severe syndromes. morbilliviruses are enveloped viruses with two envelope proteins, one of which is hemagglutinin (h) protein, which plays a role in binding to cellular receptors. during morbillivirus infection, the virus initially targets lymphoid cells and replicates efficiently in the lymph nodes. the principal cellular re ...201222403577
accuracy of a point-of-care elisa test kit for predicting the presence of protective canine parvovirus and canine distemper virus antibody concentrations in dogs.canine parvovirus (cpv) and canine distemper virus (cdv) are highly infectious and often fatal diseases with worldwide distributions, and are important population management considerations in animal shelters. a point-of-care elisa test kit is available to detect serum antibodies to cpv and cdv, and presumptively to predict protective status. the aim of this study was to determine the diagnostic accuracy of the test compared to cpv hemagglutination inhibition titers and cdv serum neutralization t ...201222381707
emergence of canine distemper virus strains with modified molecular signature and enhanced neuronal tropism leading to high mortality in wild carnivores.an ongoing canine distemper epidemic was first detected in switzerland in the spring of 2009. compared to previous local canine distemper outbreaks, it was characterized by unusually high morbidity and mortality, rapid spread over the country, and susceptibility of several wild carnivore species. here, the authors describe the associated pathologic changes and phylogenetic and biological features of a multiple highly virulent canine distemper virus (cdv) strain detected in and/or isolated from r ...201222362965
detection by hemi-nested reverse transcription polymerase chain reaction and genetic characterization of wild type strains of canine distemper virus in suspected infected dogs.a new highly sensitive and specific hemi-nested reverse transcription polymerase chain reaction (rt-pcr) assay was applied to detect nucleoprotein (np) gene of canine distemper virus (cdv) in samples collected from dogs showing respiratory, gastrointestinal, and neurological signs. thirty-eight out of 86 samples were positive suggesting that despite the vaccination, canine distemper may still represent a high risk to the canine population. the 968 base pair (bp) fragments from the hemagglutinin ...201222362940
elements in the canine distemper virus m 3' utr contribute to control of replication efficiency and virulence.canine distemper virus (cdv) is a negative-sense, single-stranded rna virus within the genus morbillivirus and the family paramyxoviridae. the morbillivirus genome is composed of six transcriptional units that are separated by untranslated regions (utrs), which are relatively uniform in length, with the exception of the utr between the matrix (m) and fusion (f) genes. this utr is at least three times longer and in the case of cdv also highly variable. exchange of the m-f region between different ...201222348107
canine distemper virus epithelial cell infection is required for clinical disease but not for immunosuppression.to characterize the importance of infection of epithelial cells for morbillivirus pathogenesis, we took advantage of the severe disease caused by canine distemper virus (cdv) in ferrets. to obtain a cdv that was unable to enter epithelial cells but retained the ability to enter immune cells, we transferred to its attachment (h) protein two mutations shown to interfere with the interaction of measles virus h with its epithelial receptor, human nectin-4. as expected for an epithelial receptor (epr ...201222278252
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
molecular detection of viral agents in free-ranging and captive neotropical felids in brazil.we describe molecular testing for felid alphaherpesvirus 1 (fhv-1), carnivore protoparvovirus 1 (cppv-1), feline calicivirus (fcv), alphacoronavirus 1 (feline coronavirus [fcov]), feline leukemia virus (felv), feline immunodeficiency virus (fiv), and canine distemper virus (cdv) in whole blood samples of 109 free-ranging and 68 captive neotropical felids from brazil. samples from 2 jaguars ( panthera onca) and 1 oncilla ( leopardus tigrinus) were positive for fhv-1; 2 jaguars, 1 puma ( puma conc ...201728677421
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
dimerization efficiency of canine distemper virus matrix protein regulates membrane budding activity.paramyxoviruses rely on the matrix (m) protein to orchestrate viral assembly and budding at the plasma membrane. although mechanistic details remain largely unknown, structural data suggested that m dimers and/or higher oligomers may facilitate membrane budding. to gain functional insights, we here employed a structure-guided mutagenesis approach to investigate the role of canine distemper virus (cdv) m protein self-assembly in membrane budding activity. three six-alanine-scan (6a) block mutants ...201728592541
rapid and sensitive detection of canine distemper virus by real-time reverse transcription recombinase polymerase amplification.canine distemper, caused by canine distemper virus (cdv), is a highly contagious and fatal systemic disease in free-living and captive carnivores worldwide. recombinase polymerase amplification (rpa), as an isothermal gene amplification technique, has been explored for the molecular detection of diverse pathogens.201728810858
surveillance for antibodies against six canine viruses in wild raccoons (procyon lotor) in japan.raccoons (procyon lotor) are found worldwide. they are frequently seen in crowded inner cities as well as in forests or wooded areas, often living in proximity to humans and their pets. we examined sera from 100 wild raccoons in japan for antibodies to six canine viruses with veterinary significance to assess their potential as reservoirs. we also aimed to understand the distribution of potentially infected wildlife. we found that 7% of samples were seropositive for canine distemper virus (cdv), ...201728715293
a molecular survey for selected viral enteropathogens revealed a limited role of canine circovirus in the development of canine acute gastroenteritis.canine circovirus (caninecv) is a canine virus, whose pathogenetic role is still uncertain. based on recent data suggesting its role as entheropathogen, a case-control study was conducted between 2013 and 2016 to investigate the association of caninecv with gastroenteritis in dogs, alone or in combination with other viral pathogens, including canine parvovirus (cpv), canine coronavirus (ccov) and canine distemper virus (cdv). a total of 219 dogs suffering from acute gastroenteritis disorders and ...201728532806
outbreak and genotyping of canine distemper virus in captive siberian tigers and red pandas.in this study, four canine distemper virus (cdv) strains were isolated from captive siberian tigers (panthera tigris altaica) and red pandas (ailurus fulgens) during two separate cdv outbreaks in a zoo in guangdong province, china. sequence alignment and phylogenetic analyses based on the full-length hemagglutinin (h) and fusion (f) genes showed that they were closely identical to genotype asia-1. prior to confirmation of cdv in siberian tigers, to control spread of the disease, a live attenuate ...201728811626
ribavirin and boceprevir are able to reduce canine distemper virus growth in vitro.canine distemper virus (cdv) is a major infectious disease of dogs. although vaccines were successful to control cdv spread in canine population, the disease is still common and may pose a threat to unvaccinated dogs. in the attempt to develop specific anti-viral therapeutic tools, the efficacy of several molecules against cdv has been investigated in vitro. in this study the antiviral efficacy in vitro against cdv of ribavirin and boceprevir alone or in combination was evaluated. cdv growth in ...201728760649
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