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Retrospective differentiation of canine distemper virus and phocine distemper virus in phocids

JOURNAL OF WILDLIFE DISEASES 2004年第1期40卷 53-59页

作者： Stanton, JB Brown, CC Poet, S Lipscomb, TP Saliki, J Frasca, S Washington State Univ Dept Vet Microbiol & Pathol Pullman WA 99164 USA Univ Georgia Coll Vet Med Dept Pathol Athens GA 30602 USA Univ Georgia Coll Vet Med Dept Med Microbiol & Parasitol Athens GA 30602 USA Armed Forces Inst Pathol Washington DC 20306 USA Oklahoma State Univ Coll Vet Med Oklahoma Anim Dis Diagnost Lab Stillwater OK 74078 USA Oklahoma State Univ Coll Vet Med Dept Vet Pathol Stillwater OK 74078 USA Univ Connecticut Dept Pathobiol & Vet Sci Storrs CT 06269 USA

Formalin-fixed paraffin-embedded tissues from one Caspian seal (Phoca caspica), one harp seal (Phoca groenlandica), one hooded seal (Cystophora cristata), and one harbor seal (Phoca vitulina vitulina) were used to compare the utility of immunohistochemistry (IHC) versus that of a novel seminested reverse transcriptase polymerase chain reaction (RT-PCR) to detect and differentiate canine distemper virus (cdv) and phocine distemper virus (PDV). Four antibodies made against PDV were able to detect both viruses. Two antibodies made against cetacean morbillivirus (CMV) did not label antigens from either cdv or PDV A third anti-CMV antibody inconsistently stained cdv antigens but did not label PDV antigens. The seminested RT-PCR was able to detect RNA of the phosphoprotein gene in all positive cases. Nucleotide sequence analyses of seminested RT-PCR products were used to differentiate cdv RNA from PDV RNA. From these data, it was determined that IHC using antibodies generated against PDV provided a rapid means of detection for both cdv and PDV antigens;however, differentiation between cdv and PDV was achieved only with the RT-PCR assay.

关键词： canine distemper cdv immunohistochemistry phocine distemper PDV RT-PCR seal

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Immunization with plasmid DNA encoding the hemagglutinin and the nucleoprotein confers robust protection against a lethal canine distemper virus challenge

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VACCINE 2004年第27-28期22卷 3642-3648页

作者： Dahl, L Jensen, TH Gottschalck, E Karlskov-Mortensen, P Jensen, TD Nielsen, L Andersen, MK Buckland, R Wild, TF Blixenkrone-Moller, M Royal Vet & Agr Univ Dept Vet Microbiol Lab Virol & Immunol DK-1870 Frederiksberg C Denmark CERVI IFR 128 Biosci Lyon Gerland INSERM Unite 404 Lyon France

We have investigated the protective effect of immunization of a highly susceptible natural host of canine distemper virus (cdv) with DNA plasmids encoding the viral nucleoprotein (N) and hemagglutinin (H). The combined intradermal and intramuscular routes of immunization elicited high virus-neutralizing serum antibody titres in mink (Mustela vison). To mimic natural exposure, we also conducted challenge infection by horizontal transmission from infected contact animals. Other groups received a lethal challenge infection by administration to the mucosae of the respiratory tract and into the muscle. One of the mink vaccinated with N plasmid alone developed severe disease after challenge. In contrast, vaccination with the H plasmid together with the N plasmid conferred solid protection against disease and we were unable to detect cdv infection in PBMCs or in different tissues after challenge. Our findings show that DNA immunization by the combined intradermal and intramuscular routes can confer solid protective immunity against naturally transmitted morbillivirus infection and disease. (C) 2004 Elsevier Ltd. All rights reserved.

关键词： cdv morbillivirus DNA immunization

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Molecular analysis of the full-length F gene of Brazilian strains of canine distemper virus shows lineage co-circulation and variability between field and vaccine strains

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VIRUS RESEARCH 2019年 264卷 8-15页

作者： Freitas, Luana Almeida Leme, Raquel Arruda Saporiti, Viviane Alfieri, Amauri Alcindo Alfieri, Alice Fernandes Univ Estadual Londrina Dept Vet Prevent Med Lab Anim Virol Rodovia Celso Garcia Cid Campus UnivPOB 10011 BR-86057970 Londrina Parana Brazil Univ Estadual Londrina Dept Vet Prevent Med Mol Biol Unit Multiuser Anim Hlth Lab Rodovia Celso Garcia Cid Campus UnivPOB 10011 BR-86057970 Londrina Parana Brazil

Canine distemper is a highly contagious systemic viral disease, with worldwide distribution that affects a wide variety of terrestrial carnivores. This study characterized full-length fusion (F) genes from 15 Brazilian wild-type canine distemper virus (cdv) strains collected between 2003-2004 (n = 6) and 2013-2016 (n = 9). Using deduced amino acid (aa) sequence analysis, 14 strains were classified into Europe 1/South America 1 (EU1/SA1) lineage, with a temporal clustering into past (2003-2004) and contemporary (2013-2016) strains. One strain clustered to Rockborn-like lineage, showing high similarity (98.5%) with the Rockborn vaccine strain. In analyzed strains, the fusion protein signal-peptide (Fsp) coding region was highly variable at the aa level (67.4%-96.2%). The Brazilian strains were more Fsp-divergent from the North America 1 (NA1) strains (24.5%-36.3%) than from the Rockborn (11.2%-14.9%) vaccine strain. Seventeen cysteine residues in the full-length F gene and four non-conserved glycosylation sites in the Fsp region were detected. The results reveal that past and contemporary cdv strains are currently co-circulating. This first analysis of full-length F genes from Brazilian wild-type cdv strains contributes to knowledge of molecular epidemiology of cdv viral infection and evolution.

关键词： Paramyxovirus cdv Fusion protein Fsp-coding region Rockborn-like lineage Molecular epidemiology

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Evaluation of synthetic infection-enhancing lipopeptides as adjuvants for a live-attenuated canine distemper virus vaccine administered intra-nasally to ferrets

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VACCINE 2012年第34期30卷 5073-5080页

作者： Nguyen, D. Tien Ludlow, Martin van Amerongen, Geert de Vries, Rory D. Yuksel, Selma Verburgh, R. Joyce Osterhaus, Albert D. M. E. Duprex, W. Paul de Swart, Rik L. Erasmus MC Dept Virol Univ Med Ctr NL-3000 CA Rotterdam Netherlands Boston Univ Dept Microbiol Sch Med Boston MA 02118 USA Boston Univ Natl Emerging Infect Dis Labs Boston MA 02118 USA

Background: 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 adjuvants to promote immune responses induced by live-attenuated paramyxovirus vaccines. Methods: Here, we tested this hypothesis using a cdv vaccination and challenge model in ferrets. Three groups of six animals were intra-nasally vaccinated with recombinant (r) (cdvL)-L-5804P(CCEGFPC) in the presence or absence of the infection-enhancing lipopeptides Pam3CSK4 or PHCSK4. The recombinant cdv vaccine virus had previously been described to be over-attenuated in ferrets. A group of six animals was mock-vaccinated as control. Six weeks after vaccination all animals were challenged with a lethal dose of rcdv strain Snyder-Hill expressing the red fluorescent protein dTomato. Results: Unexpectedly, intra-nasal vaccination of ferrets with rcdv(5804P)L(CCEGFPC) in the absence of lipopeptides resulted in good immune responses and protection against lethal challenge infection. However, in animals vaccinated with lipopeptide-adjuvanted virus significantly higher vaccine virus loads were detected in nasopharyngeal lavages and peripheral blood mononuclear cells. In addition, these animals developed significantly higher cdv neutralizing antibody titers compared to animals vaccinated with non-adjuvanted vaccine. Conclusions: This study demonstrates that the synthetic cationic lipopeptides Pam3CSK4 and PHCSK4 not only enhance paramyxovirus infection in vitro, but also in vivo. Given the observed enhancement of immunogenicity their potential as adjuvants for other live-attenuated paramyx

关键词： Lipopeptide Adjuvant Live-attenuated virus vaccine cdv Paramyxovirus

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A new tool linking human cytomegalovirus drug resistance mutations to resistance phenotypes

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ANTIVIRAL RESEARCH 2010年第2期85卷 318-327页

作者： Chevillotte, Meike von Einem, Jens Meier, Benjamin M. Lin, Feng-Mao Kestler, Hans A. Mertens, Thomas Univ Ulm Inst Neural Informat Proc D-89069 Ulm Germany Univ Hosp Ulm Inst Virol D-89081 Ulm Germany Natl Chiao Tung Univ Inst Bioinformat & Syst Biol Hsinchu 300 Taiwan

Drug resistant strains of human cytomegalovirus (HCMV) in patients at risk may increasingly develop into a problem in the clinical setting. Genotypic resistance testing is becoming the method of choice, but requires previous phenotypic characterisation of each newly found mutation. In order to facilitate the interpretation of the patient's CMV sequence data, a web-based search tool was generated that links the sequence to a database containing all published UL97 (protein kinase) and UL54 (DNA polymerase) mutations and corresponding antiviral drug susceptibility phenotypes. It is reasonable to assume that HCMV drug resistance testing will provide relevant data for an adjustment of therapy and on prognosis of clinical outcome. HCMV drug susceptibility testing will become even more important once new drugs will be available for therapy allowing a wider choice of antiviral agents to treat HCMV disease. These topics will also play a pivotal role for optimising antiviral therapy of HCMV- and other viral diseases. (C) 2009 Elsevier B.V. All rights reserved.

关键词： UL97 UL54 Genotype Clinical outcome HCMV GCV cdv FOS

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Canine microglial cells:: Stereotypy in immunophenotype and specificity in function?

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VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY 2006年第3-4期113卷 277-287页

作者： Stein, Veronika M. Baumgaertner, Wolfgang Kreienbrock, Lothar Zurbriggen, Andreas Vandevelde, Marc Tipold, Andrea Univ Vet Med Dept Small Anim Med & Surg D-30173 Hannover Germany Ctr Syst Neurosci D-30173 Hannover Germany Univ Vet Med Inst Pathol Hannover Germany Univ Vet Med Inst Biometry Epidemiol & Informat Proc Hannover Germany Univ Bern Inst Anim Neurol Bern Switzerland

Microglial cells represent the endogenous immune system of the central nervous system (CNS). Upon pathological insults they reveal their immunological potential aimed at regaining homeostasis. These reactions have long been believed to follow a uniform and unspecific pattern which is irrespective to the underlying disease entity. Evidence is growing that this view seriously underrates microglial competence as the defenders of the CNS. In the present study, microglial cells of 47 dogs were examined ex vivo by means of flow cytometry. Ex vivo examination included immunophenotypic characterization using eight different surface markers and functional studies such as phagocytosis assay and the reactive oxygen species (ROS) generation test. The dogs were classified according to their histopathological diagnoses in disease categories (controls, canine distemper virus (cdv) induced demyelination, other diseases of the CNS) and results of microglial reaction profiles were compared. Immunophenotypic characterization generally revealed relative high conformity in the microglial disease response among the different groups, however the functional response was shown to be more specific. Dogs with intracranial inflammation and dogs with demyelination showed an enhanced phagocytosis, whereas a significant up-regulation of ROS generation was found in dogs with demyelination due to cdv infection. This strongly suggests a specific response of microglia to infection with cdv in the settings of our study and underlines the pivotal role of microglial ROS generation in the pathogenesis of demyelinating diseases, such as canine distemper. (c) 2006 Elsevier B.V. All rights reserved.

关键词： canine microglia stereotypic versus specific reaction ex vivo examination surface molecules ROS phagocytosis demyelination cdv

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A novel and highly divergent Canine Distemper Virus lineage causing distemper in ferrets in Australia

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VIROLOGY 2022年 576卷 117-126页

作者： George, Ankita M. Wille, Michelle Wang, Jianning Anderson, Keith Cohen, Shari Moselen, Jean Lee, Leo Y. Y. Suen, Willy W. Bingham, John Dalziel, Antonia E. Whitney, Paul Stannard, Harry Hurt, Aeron C. Williams, David T. Deng, Yi-Mo Barr, Ian G. WHO Collaborating Ctr Reference & Res Influenza Peter Doherty Inst Infect & Immun Melbourne Vic Australia Univ Sydney Sch Med Sci Sydney NSW Australia Univ Sydney Sydney Inst Infect Dis Sch Life & Environm Sci Sydney NSW Australia Univ Melbourne Peter Doherty Inst Infect & Immun Dept Microbiol & Immunol Melbourne Vic Australia CSIRO Australian Ctr Dis Preparedness Geelong Vic Australia Univ Melbourne Off Res Ethics & Integr Melbourne Vic Australia

Canine distemper virus (cdv) causes a highly contagious systemic infection in an array of animal species. In this study we report an outbreak of distemper in ferrets in two research facilities in Australia, caused by a novel lineage of cdv. While the cdv strain caused mainly mild symptoms in ferrets, histopathology results presented a typical profile of distemper pathology, with multi-system virus replication. Through the development of a discriminatory PCR, paired with full genome sequencing, we revealed that the outbreak was caused by a novel lineage of cdv. The novel cdv lineage was highly divergent, with less than 93% similarity across the H gene to other described lineages, including the vaccine strain, and diverged approximately 140-400 years ago. Enhanced surveillance to determine the prevalence of cdv in ferrets, dogs and other at-risk species is critical to better understand the presence and diversity of cdv in Australia currently.

关键词： Canine distemper virus Canine morbillivirus Paramyxoviridae cdv Ferrets Australia

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Constrained disequilibrium values and hitchhiking in a three-locus system

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GENETICS 1998年第3期150卷 1295-1307页

作者： Grote, MN Klitz, W Thomson, G Univ Calif Davis Sect Evolut & Ecol Davis CA 95616 USA Univ Calif Berkeley Sch Publ Hlth Berkeley CA 94720 USA Univ Calif Berkeley Dept Integrat Biol Berkeley CA 94720 USA

Positive selection on a new mutant allele can increase the frequencies of closely linked alleles (through hitchhiking), as well as create linkage disequilibrium between them. Because this disequilibrium is induced by the selected allele, one may be able to identify loci under selection by measuring the influence of a candidate locus on pairwise disequilibrium values at nearby loci. The constrained disequilibrium values (cdv) method approaches this problem by examining differences in pairwise disequilibrium values, which have been normalized for two- and three-locus systems, respectively. We have investigated in detail the reliability of inferences based on cdv, using simulation and analytical methods. Our main results are (i) in some circumstances, cdv may not distinguish well between a selected locus and a neighboring neutral locus, but (ii) cdv seldom indicates "selection" in neutral haplotypes with moderate to large 4Nc. We conclude that, although the cdv method does not appear to precisely locate selected alleles, it can be used to screen for regions in which hitchhiking is a plausible hypothesis. We present a microsatellite data set from human chromosome 6, in which constrained disequilibrium values suggest the action of selection in a region containing the human leukocyte antigen (HLA)A and myelin oligodendrocyte glycoprotein (MOG) loci. The connection between hitchhiking and disequilibrium has received relatively little attention, so our investigation presents opportunities to address more general issues.

关键词： .pairwise closely linked Three-locus hitchhiking New Mutant cdv Constrained Disequilibrium

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Plagues and adaptation: Lessons from the Felidae models for SARS and AIDS

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BIOLOGICAL CONSERVATION 2006年第2期131卷 255-267页

作者： O'Brien, Stephen J. Troyer, Jennifer L. Roelke, Melody Marker, Laurie Pecon-Slattery, Jill Natl Canc Inst Lab Genom Divers Ft Detrick MD 21702 USA NCI Lab Genom Divers SAIC Frederick Frederick MD USA

Research studies of infectious disease outbreaks in wild species of the cat family Felidae have revealed unusual details regarding forces that shape population survival and genetic resistance in these species. A highly virulent feline coronavirus epidemic in African cheetahs, a disease model for human SARS, illustrates the critical role of ancestral population genetic variation. Widespread prevalence of species specific feline immunodeficiency virus (FM, a relative of HIV-AIDS, occurs with little pathogenesis in felid species, except in domestic cats, suggesting immunological adaptation in species where FIV is endemic. Resolving the interaction of host and pathogen genomes can shed new light on the process of disease outbreak in wildlife and in humankind. The role of disease in endangered populations and species is difficult to access as opportunities to monitor outbreaks in natural populations are limited. Conservation management may benefit greatly from advances in molecular genetic tools developed for human biomedical research to assay the biodiversity of both host species and emerging pathogen. As these examples illustrate, strong parallels exist between disease in human and endangered wildlife and argue for an integration of the research fields of comparative genomics, infectious disease, epidemiology, molecular genetics and population biology for an effective proactive conservation approach. (c) 2006 Elsevier Ltd. All rights reserved.

关键词： FIV SARS AIDS cdv

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MITOGEN AND ANTIGEN-INDUCED B-CELL AND T-CELL RESPONSES OF PERIPHERAL-BLOOD MONONUCLEAR-CELLS FROM THE HARBOR SEAL (PHOCA-VITULINA)

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VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY 1993年第3-4期37卷 217-230页

作者： DESWART, RL KLUTEN, RMG HUIZING, CJ VEDDER, LJ REIJNDERS, PJH VISSER, IKG UYTDEHAAG, FGCM OSTERHAUS, ADME SEAL REHABIL & RES CTR 9968 AG PIETERBURENNETHERLANDS INST FORESTRY & NAT RES 1790 AB DEN BURGNETHERLANDS

In vitro assays were developed for studies concerning the functioning of the immune system of the harbour seal (Phoca vitulina). Proliferative responses of peripheral blood mononuclear cells (PBMC) were measured after stimulation with different concentrations of the mitogens concanavalin A (Con A), pokeweed mitogen (PWM), phytohaemagglutinin (PHA) or lipopolysaccharide from Salmonella typhimurium (LPS). Con A and PWM induced strong proliferative responses, while PHA and LPS induced comparatively low proliferative responses. Responses of mitogen stimulated PBMC to recombinant human interleukin-2 (rhIL-2) and in vitro immunoglobulin production by mitogen stimulated PBMC were measured to discriminate between stimulation of T cells and B cells. It was found that Con A and PHA stimulate phocine T cells, PWM stimulates both T cells and B cells and LPS predominantly stimulates phocine B cells. Antigen-specific immune responses were measured after immunization of seals with an inactivated rabies vaccine and/or with tetanus toxoid. Antigen-specific proliferation of PBMC and the presence of antigen-specific antibody forming cells were demonstrated for both antigens in the PBMC of immunized animals. The responses measured in vitro correlated well with the development of specific serum antibody titers to these antigens.

关键词： Ab antibody AFC antibody forming cells Ag antigen cdv canine distemper virus CM culture medium Con A concanavalin A cpm counts per minute ELISA enzyme linked immunosorbent assay FBS fetal bovine serum 3 H-Trd tritium labeled thymidin IU international units LF flocculation unit LPS lipopolysaccharide from Salmonella typhimurium PBMC peripheral blood mononuclear cells PBS phosphate buffered saline PDV phocine distemper virus PHA phytohaemagglutinin PWM pokeweed mitogen rhIL-2 recombinant human interleukin-2 RV rabies virus antigen SD standard deviation SI stimulation index TT tetanus toxoid 5-BCIP 5-bromo-4-chloro-3-indolyl phosphate

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