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Sequencing of emerging canine distemper virus strain reveals new distinct genetic lineage in the United States associated with disease in wildlife and domestic canine populations

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VIROLOGY JOURNAL 2015年第1期12卷 1-10页

作者： Riley, Matthew C. Wilkes, Rebecca P. Univ Tennessee Dept Biomed & Diagnost Sci Coll Vet Med Knoxville TN 37996 USA US Army Med Serv Corps Salt Lake City UT USA

Background: Recent outbreaks of canine distemper have prompted examination of strains from clinical samples submitted to the University of Tennessee College of Veterinary Medicine (UTCVM) Clinical Virology Lab. We previously described a new strain of cdv that significantly diverged from all genotypes reported to date including America 2, the genotype proposed to be the main lineage currently circulating in the US. The aim of this study was to determine when this new strain appeared and how widespread it is in animal populations, given that it has also been detected in fully vaccinated adult dogs. Additionally, we sequenced complete viral genomes to characterize the strain and determine if variation is confined to known variable regions of the genome or if the changes are also present in more conserved regions. Methods: Archived clinical samples were genotyped using real-time RT-PCR amplification and sequencing. The genomes of two unrelated viruses from a dog and fox each from a different state were sequenced and aligned with previously published genomes. Phylogenetic analysis was performed using coding, non-coding and genome-length sequences. Virus neutralization assays were used to evaluate potential antigenic differences between this strain and a vaccine strain and mixed ANOVA test was used to compare the titers. Results: Genotyping revealed this strain first appeared in 2011 and was detected in dogs from multiple states in the Southeast region of the United States. It was the main strain detected among the clinical samples that were typed from 2011-2013, including wildlife submissions. Genome sequencing demonstrated that it is highly conserved within a new lineage and preliminary serologic testing showed significant differences in neutralizing antibody titers between this strain and the strain commonly used in vaccines. Conclusion: This new strain represents an emerging cdv in domestic dogs in the US, may be associated with a stable reservoir in the wildlife popu

关键词： Canine distemper virus cdv Genome sequencing New cdv strain Phylogenetics Vaccination Vaccines

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Involvement of apoptosis in syncytial cell death induced by canine distemper virus

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COMPARATIVE IMMUNOLOGY MICROBIOLOGY AND INFECTIOUS DISEASES 2004年第6期27卷 445-455页

作者： Nishi, T Tsukiyama-Kohara, K Togashi, K Kohriyama, N Kai, C Univ Tokyo Inst Med Sci Lab Anim Res Ctr Minato Ku Tokyo 1088639 Japan

The Yanaka strain, a field isolate of Canine distemper virus (cdv), caused extensive syncytial cytopathic effects (CPEs) followed by cell death in vitro. Syncytium formation is an important aspect of cdv pathogenicity, but the mechanism of the fusion-induced cell death is still not understood. In this study, the involvement of apoptosis in the cdv-induced CPE was investigated. We also examined apoptosis in cells infected with a persistent strain of cdv, the Yanaka-BP strain derived from the Yanaka strain, because this strain does not cause obvious CPE. DNA laddering together with Terminal transferase dUTP nick endlabeling (TUNEL) assay indicated that the Yanaka strain infection, but not the Yanaka-BP infection induced apoptosis. In addition, flow cytometric analysis similarly indicated that the Yanaka-BP strain induced apoptosis significantly less frequently than the Yanaka strain did. Thus, absence of apoptosis may be implicated in the CPE and establishment of persistent cdv infection. (C) 2004 Elsevier Ltd. All rights reserved.

关键词： apoptosis cdv CPE persistent strain

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The V domain of dog PVRL4 (nectin-4) mediates canine distemper virus entry and virus cell-to-cell spread

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VIROLOGY 2014年第1期454卷 109-117页

作者： Delpeut, Sebastien Noyce, Ryan S. Richardson, Christopher D. Dalhousie Univ Dept Microbiol & Immunol Halifax NS B3H 1X5 Canada Canadian Ctr Vaccinol IWK Hlth Ctr Halifax NS B3H 1X5 Canada Dalhousie Univ Dept Pediat Halifax NS B3H 1X5 Canada

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 dog PVRL4 and two within the cdv hemagglutinin were shown to be essential for receptor-mediated virus entry. (C) 2014 Elsevier Inc. All rights reserved.

关键词： Nectin-4 PVRL4 Poliovirus receptor-like protein-4 Receptor V domain Epithelial cell Canine distemper virus cdv Hemagglutinin Virus entry Syncytia formation

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An immunochromatography assay for rapid antemortem diagnosis of dogs suspected to have canine distemper

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JOURNAL OF VIROLOGICAL METHODS 2008年第2期147卷 244-249页

作者： An, Dong-Jun Kim, Tae-Young Song, Dae-Sub Kang, Bo-Kyu Park, Bong-Kyun Seoul Natl Univ Coll Vet Med Seoul 151742 South Korea Seoul Natl Univ BK21 Program Vet Sci Seoul 151742 South Korea Natl Vet Res & Quarantine Serv Anyang 430824 Kyunggi Do South Korea HBI Corp Anyang 430824 Kyunggi Do South Korea Green Cross Vet Products Res Unit Yongin 449903 South Korea

A new assay was developed for rapid and antemortem diagnosis of canine distemper (CD). This immunochromatography (IC)-based assay, which employs two monoclonal anti-cdv antibodies, was compared with nested PCR. When serial dilutions of purified cdv were tested, the cdv detection limits of the nested PCR and IC assays were 2 x 10(2) TCID50/Ml and 5 x 10(2) TCID50/Ml, respectively. Nasal irrigation fluid, conjunctival swabs, and blood lymphocytes from 66 dogs suspected to have CD were tested Preliminary IC experiments revealed that the optimal sample volume and reaction time were 100 mu l and 5 min. respectively. Relative to nested PCR, the sensitivity and specificity of the IC assay was maximal (100% and 100%, respectively) when conjunctival swabs were tested. This is significant because conjunctival swab specimens are easy to obtain in the early phase of CD infection. However, with blood lymphocytes and nasal samples, the IC assay was slightly less sensitive (89.7% and 85.7%, respectively) and specific (94.6% and 100%, respectively) than nested PCR. Since this novel IC assay does not require special instruments, it is a simple enough for dog owners to use. Since early detection of CD would allow appropriate treatment and quarantine to be instituted quickly, such a test would help reduce the morbidity and mortality associated with CD help to prevent its spread to other animals. (c) 2007 Elsevier B.V. All rights reserved.

关键词： cdv immunochromatography PCR

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Down regulation of melanin concentrating hormone in virally induced obesity

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MOLECULAR AND CELLULAR ENDOCRINOLOGY 2001年第1-2期181卷 207-219页

作者： Verlaeten, O Griffond, B Khuth, ST Giraudon, P Akaoka, H Belin, MF Fellmann, D Bernard, A RTH Laennec Fac Med INSERM U433 F-69372 Lyon 08 France Fac Med & Pharm CNRS ESA 6025 Lab Histol Embryol Cytogenet FR 51Inst Etud & Transfert Genes F-25030 Besancon France

Obesity is a complex disease involving genetic components and environmental factors and probably associated with the dysregulation of central homeostasis normally maintained by the hypothalamic neuroendocrine/neurotransmitter network. We previously reported that canine distemper virus (cdv), which is closely related to human measles virus, can target hypothalamic nuclei, and lead to obesity syndrome in the late stages of infection. Here, using differential display PCR, we demonstrate specific down-regulation of melanin-concentrating hormone precursor mRNA (ppMCH) in infected-obese mice. Although ppMCH was down-regulated in all infected mice during the acute stage of infection, this was only seen during the late stage of infection in infected-obese mice. In addition, ppMCH mRNA and protein expression in the lateral hypothalamus was decreased in the absence of neuronal death. These results show the importance of ppMCH in the establishment and maintenance of obesity and the involvement of a virus as an environmental factor. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

关键词： MCH hypothalamus cdv obesity DDRT-PCR mouse hypothalamus

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Silver nanoparticles composition for treatment of distemper in dogs

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INTERNATIONAL JOURNAL OF NANOTECHNOLOGY 2016年第1-3期13卷 227-237页

作者： Bogdanchikova, Nina Vazquez-Munoz, Roberto Huerta-Saquero, Alejandro Pena-Jasso, Antonio Aguilar-Uzcanga, Gildardo Picos-Diaz, Paola L. Pestryakov, Alexey Burmistrov, Vasilii Martynyuk, Oxana Luna-Vazquez-Gomez, Roberto Almanza, Horacio Univ Nacl Autonoma Mexico Ctr Nanociencias & Nanotecnol Km 107 Carretera Tijuana Ensenada Ensenada 22860 Baja California Mexico Hosp Vet Blvd Costero 1548 Ensenada Baja California Mexico Ctr Vet Aguzvet Ensenada Ctr Ruiz 1373 Ensenada 22800 Baja California Mexico Clin Vet Albeitar Blvd PopotlaCarr Libre Tijuana Ensenada 742 Rosarito BC Mexico Tomsk Polytech Univ Dept Technol Organ Subst & Polymer Mat Tomsk 634050 Russia Res & Prod Ctr Vector Vita Ltd Novosibirsk Russia Tomsk Polytech Univ Tomsk 634050 Russia Univ Autonoma Baja California Carr Ensenada Tijuana 3917 Ensenada 22860 Baja California Mexico

Canine distemper is caused by the canine distemper virus (cdv), a paramyxovirus of the genus Morbillivirus, with a worldwide distribution. Canine distemper is a multisystem disease, potentially fatal. Affected organisms may develop clinical or subclinical infections, among them respiratory, gastrointestinal and of the nervous system. In the present work, we use a veterinary pharmaceutical composition of silver nanoparticles (AgNPs) for the treatment of distemper in dogs with neurological and non-neurological symptoms. AgNPs treatment of animals with non-neurological distemper provides a very high rate of recovery without sequelae. However, in dogs with neurological symptoms, AgNPs treatment was not able to reverse the disease.

关键词： AgNPs treatment canine distemper virus cdv distemper virus silver nanoparticles

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Efficient generation of vesicular stomatitis virus (VSV)-pseudotypes bearing morbilliviral glycoproteins and their use in quantifying virus neutralising antibodies

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VACCINE 2016年第6期34卷 814-822页

作者： Logan, Nicola McMonagle, Elizabeth Drew, Angharad A. Takahashi, Emi McDonald, Michael Baron, Michael D. Gilbert, Martin Cleaveland, Sarah Haydon, Daniel T. Hosie, Margaret J. Willett, Brian J. Univ Glasgow MRC Ctr Virus Res Garscube Estate Glasgow G61 1QH Lanark Scotland Univ London Royal Vet Coll 32 Belgrave Sq London NW1 0TU England Univ Glasgow Vet Diagnost Serv Garscube Estate Glasgow G61 1QH Lanark Scotland Pirbright Inst Pirbright GU24 0NF Surrey England Wildlife Conservat Soc Bronx NY USA Univ Glasgow Inst Biodivers Anim Hlth & Comparat Med Boyd Orr Ctr Populat & Ecosyst Hlth Glasgow G12 8QQ Lanark Scotland

Morbillivirus neutralising antibodies are traditionally measured using either plaque reduction neutralisation tests (PRNTs) or live virus microneutralisation tests (micro-NTs). While both test formats provide a reliable assessment of the strength and specificity of the humoral response, they are restricted by the limited number of viral strains that can be studied and often present significant biological safety concerns to the operator. In this study, we describe the adaptation of a replication-defective vesicular stomatitis virus (VSV Delta G) based pseudotyping system for the measurement of morbillivirus neutralising antibodies. By expressing the haemagglutinin (H) and fusion (F) proteins of canine distemper virus (cdv) on VSV Delta G pseudotypes bearing a luciferase marker gene, neutralising antibody titres could be measured rapidly and with high sensitivity. Further, by exchanging the glycoprotein expression construct, responses against distinct viral strains or species may be measured. Using this technique, we demonstrate cross neutralisation between cdv and peste des petits ruminants virus (PPRV). As an example of the value of the technique, we demonstrate that UK dogs vary in the breadth of immunity induced by cdv vaccination;in some dogs the neutralising response is cdv-specific while, in others, the neutralising response extends to the ruminant morbillivirus PPRV. This technique will facilitate a comprehensive comparison of cross-neutralisation to be conducted across the morbilliviruses. (C) 2015 The Authors. Published by Elsevier Ltd.

关键词： Morbillivirus Neutralisation cdv PPRV Pseudotype

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Identification of a new polymorphism on the wild-type canine distemper virus genome: could this contribute to vaccine failures?

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BRAZILIAN JOURNAL OF MICROBIOLOGY 2023年第2期54卷 665-678页

作者： Menezes, Karolina Martins Ferreira Dabilla, Nathania Souza, Menira Damasceno, Adilson Donizeti Torres, Bruno Benetti Junta Univ Fed Goias UFG Escola Vet & Zootecnia Campus 2 BR-74690900 Goiania GO Brazil Univ Fed Goias Inst Patol Trop & Saude Publ Goiania GO Brazil

The canine distemper virus (cdv) is responsible for a multisystem infectious disease with high prevalence in dogs and wild carnivores and has vaccination as the main control measure. However, recent studies show an increase in cases including vaccinated dogs in different parts of the world. There are several reasons for vaccine failures, including differences between vaccine strains and wild-type strains. In this study, a phylogenetic analysis of cdv strains from samples of naturally infected, vaccinated, and symptomatic dogs in Goiania, Goias, Brazil was performed with partial sequencing of the hemagglutinin (H) gene of cdv. Different sites of amino acid substitutions were found, and one strain had the Y549H mutation, typically present in samples from wild animals. Substitutions in epitopes (residues 367, 376, 379, 381, 386, and 388) that may interfere with the vaccine's ability to provide adequate protection against infection for cdv were observed. The identified strains were grouped in the South America 1/Europe lineage, with a significant difference from other lineages and vaccine strains. Twelve subgenotypes were characterized, considering a nucleotide identity of at least 98% among the strains. These findings highlight the relevance of canine distemper infection and support the need better monitoring of the circulating strains that contribute to elucidate if there is a need for vaccine update.

关键词： Viral strain cdv Genotyping Lineages Nested-PCR

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EXAMINATION OF THE IMMUNOLOGICAL RELATIONSHIP BETWEEN MEASLES-VIRUS AND CANINE-DISTEMPER VIRUS USING MONOSPECIFIC MEASLES ANTISERA

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JOURNAL OF MEDICAL VIROLOGY 1981年第1期7卷 51-60页

作者： GOULD, EA ARMSTRONG, M SHIRODARIA, PV DEORNELLAS, D QUEENS UNIV BELFAST DEPT MICROBIOL & IMMUNOBIOL BELFAST BT7 1NN ANTRIM NORTH IRELAND

Indirect immunofluorescence titrations were performed with measles virus, the Rockborn strain of canine distemper virus (cdv) and a large plaque variant of the Onderstepoort strain of cdv (Ond-LP) using monospecific antisera prepared against either the hemagglutinin (anti-HA), the hemolysin (anti-HL) or the ribonucleoprotein (anti-RNP) of measles virus. Tests with anti-HA showed that the Rockborn strain of cdv was more closely related to measles virus than Ond-LP. The ribonucleoprotein antigens of the cdv strains were closely related to each other but were both related to and distinct from measles virus RNP. The use of measles anti-HL serum demonstrated that cdv possesses an antigenically related acetone-sensitive component equivalent to the hemolysin of measles virus. Absorption of human convalescent serum with excess quantities of acetone-fixed cdv antigens had no effect on measles-specific anti-HA, HL or RNP activity in the serum. Absorption with measles antigens totally removed all measles and cdv-specific HA and RNP activity. cdv was not neutralized by any of the monospecific antisera when tested either as individual antisera or as mixtures. The occurrence of antigenic variation between different strains of cdv also reveal unique antigenic determinants in measles virus and cdv.

关键词： antigens measles cdv monospecific

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Dog nectin-4 is an epithelial cell receptor for canine distemper virus that facilitates virus entry and syncytia formation

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VIROLOGY 2013年第1期436卷 210-220页

作者： Noyce, Ryan S. Delpeut, Sebastien Richardson, Christopher D. Dalhousie Univ Dept Microbiol & Immunol Halifax NS B3H 1X5 Canada Canadian Ctr Vaccinol IWK Hlth Ctr Halifax NS B3H 1X5 Canada Dalhousie Univ Dept Pediat Halifax NS B3K 6R8 Canada

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 function as an entry factor for cdv containing an EGFP reporter gene. Inhibition of dog nectin-4 expression by RNAi or nectin-4 antibodies decreased cdv titers and EGFP fluorescence. Finally, dog nectin-4 also promotes syncytia formation, which could be inhibited by siRNA treatment. These data confirm that dog nectin-4 can be used by cdv to gain entry into epithelial cells, and facilitate virus spread. (C) 2012 Elsevier Inc. All rights reserved.

关键词： Nectin-4 PVRL4 Receptor Epithelial cell Canine distemper virus cdv MDCK

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