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At least 19 recordsLinked to original sources

Examination of eight cases of multiple sclerosis and 56 neurological and non-neurological controls for genomic sequences of measles virus, canine distemper virus, simian virus 5 and rubella virus.

In situ hybridization studies have been carried out on brain samples from eight cases of multiple sclerosis (MS) and 56 non-neurological and neurological controls, using single-stranded 35S-labelled RNA probes prepared against genomic RNA sequences of measles virus, canine distemper virus, rubella virus and simian virus 5. Foci of hybridization were found using probes against the measles virus nucleocapsid protein (N), phosphoprotein and fusion protein gene sequences in two of the MS cases, and also in one control, a case of disseminated cytomegalovirus infection with spinal cord necrosis. This result was confirmed using biotinylated probes prepared against the measles virus N genomic sequence. No hybridization was found in any of the MS or control cases using any of the other viral genome-specific probes.

Astrocytoma↗

Antiviral antibodies stimulate production of reactive oxygen species in cultured canine brain cells infected with canine distemper virus.

Canine distemper is characterized mainly by respiratory, enteric, and nervous symptoms. Infection of the central nervous system results in demyelination, to which inflammation has been shown to contribute significantly. It has been proposed that macrophages play a major role as effector cells in this process. We report that cultured dog brain cells contain a population of macrophages capable of producing reactive oxygen species as measured by luminol-dependent chemiluminescence. In cultures infected with canine distemper virus, a burst of reactive oxygen is triggered by antiviral antibody. This response depends on the presence of viral antigens on the surfaces of infected cells and is mediated by the interaction of antigen-bound antibody with Fc receptors on the macrophages. Since there is no evidence in vitro or in vivo that oligodendrocytes, the cells forming myelin, are infected, our observation supports the hypothesis that "innocent bystander killing" is important in demyelination caused by canine distemper virus. Reactive oxygen species released from macrophages may contribute to destruction of myelin.

Animals↗

CD9, a tetraspan transmembrane protein, renders cells susceptible to canine distemper virus.

Canine distemper virus (CDV), a lymphotropic and neurotropic negative-stranded RNA virus of the Morbillivirus genus, causes a life-threatening disease in several carnivores, including domestic dogs. To identify the cellular receptor(s) involved in the uptake of CDV by susceptible cells, we isolated a monoclonal antibody (MAb K41) which binds to the cell surface and inhibits the CDV infection of several cell lines from various species. Pretreatment of cells with MAb K41 reduces the number of infectious centers and the size of the syncytia. Using affinity chromatography with MAb K41, we purified from HeLa and Vero cell extracts a 26-kDa protein which contained the amino acid sequence TKDEPQRETLK of human CD9, a member of the tetraspan transmembrane or transmembrane 4 superfamily of cell surface proteins. Transfection of NIH 3T3 or MDBK cells with a CD9 expression plasmid rendered these cells permissive for viral infection and raised virus production by a factor of 10 to 100. The mechanism involved is still unclear, since we were unable to detect direct binding of CDV to CD9 by using immunoprecipitation and a virus overlay protein binding assay. These findings indicate that human CD9 and its homologs in other species are necessary factors for the uptake of CDV by target cells, the formation of syncytia, and the production of progeny virus.

3T3 Cells↗

Establishment of a rescue system for canine distemper virus.

Canine distemper virus (CDV) has been rescued from a full-length cDNA clone. Besides Measles virus (MV) and Rinderpest virus, a third morbillivirus is now available for genetic analysis using reverse genetics. A plasmid p(+)CDV was constructed by sequential cloning using the Onderstepoort vaccine strain large-plaque-forming variant. The presence of a T7 promoter allowed transcription of full-length antigenomic RNA by a T7 RNA polymerase, which was provided by a host range mutant of vaccinia virus (MVA-T7). Plasmids expressing the nucleocapsid protein, the phosphoprotein, and the viral RNA-dependent RNA polymerase, also under control of a T7 promoter, have been generated. Infection of HeLa cells with MVA-T7 and subsequent transfection of p(+)CDV plus the helper plasmids led to syncytium formation and release of infectious recombinant (r) CDV. Comparison of the rescued virus with the parental virus revealed no major differences in the progression of infection or in the shape and size of syncytia. A genetic tag, consisting of two nucleotide changes within the coding region of the L protein, has been identified in the rCDV genome. Expression by rCDV of all the major viral structural proteins has been demonstrated by immunofluorescence.

Animals↗

Presence of antibodies to canine distemper virus, canine parvovirus and canine adenovirus type 1 in free-ranging jackals (Canis adustus and Canis mesomelas) in Zimbabwe.

A survey of free-ranging jackals (Canis adustus and Canis mesomelas) in Zimbabwe was conducted to determine the prevalence of serum antibodies to canine distemper virus (CDV), canine parvovirus (CPV) and canine adenovirus type 1 (CAV-1). Sera from 16 Canis adustus and 22 Canis mesomelas were collected from 1990 to 1993 from various regions of Zimbabwe and assayed by means of immunofluorescent techniques. Seroprevalence in C. adustus and C. mesomelas respectively were 50% and 63.6% for CDV, 12.5% and 18.2% for CPV and 37.5 and 9.1 for CAV-1. These results demonstrate that jackals are infected with these viruses and may act as reservoirs of them, although their susceptibility to the viruses is not known.

Adenoviruses, Canine↗

Three-year rabies duration of immunity in dogs following vaccination with a core combination vaccine against canine distemper virus, canine adenovirus type-1, canine parvovirus, and rabies virus.

Thirty-two seronegative pups were vaccinated at 8 weeks of age with modified-live canine distemper virus (CDV), canine adenovirus type-2 (CAV-2), and canine parvovirus (CPV) vaccine and at 12 weeks with a modified-live CDV, CAV-2, CPV, and killed rabies virus vaccine. An additional 31 seronegative pups served as age-matched, nonvaccinated controls. All test dogs were strictly isolated for 3 years after receiving the second vaccination and then were challenged with virulent rabies virus. Clinical signs of rabies were prevented in 28 (88%) of the 32 vaccinated dogs. In contrast, 97% (30 of 31) of the control dogs died of rabies infection. These study results indicated that no immunogenic interference occurred between the modified-live vaccine components and the killed rabies virus component. Furthermore, these results indicated that the rabies component in the test vaccine provided protection against virulent rabies challenge in dogs 12 weeks of age or older for a minimum of 3 years following vaccination.

Adenoviridae↗

Association between cancer chemotherapy and canine distemper virus, canine parvovirus, and rabies virus antibody titers in tumor-bearing dogs.

OBJECTIVE: To determine the association between cancer chemotherapy and serum canine distemper virus (CDV), canine parvovirus (CPV), and rabies virus antibody titers in tumor-bearing dogs. DESIGN: Prospective study. ANIMALS: 21 client-owned dogs with various malignancies and 16 client-owned dogs with lymphoma. PROCEDURE: In study A, serum antibody titers were measured by use of hemagglutination inhibition (CPV titers) or serum neutralization (CDV titers) before and at least 1 month after initiation of chemotherapy. Baseline values were compared with values obtained from a control population of 122 healthy dogs seen for routine revaccination. Titers were considered protective at > or = 1:96 for CDV and > or = 1:80 for CPV. In study B, serum IgG titers were measured by use of immunofluorescent assay (CDV and CPV titers) and rapid fluorescent focus inhibition test (RFFIT, rabies titers) at baseline and again at weeks 5, 8, and 24 of a standard chemotherapy protocol for treatment of lymphoma. An IgG titer of > or = 1:50 was considered protective for CPV and CDV. An RFFIT titer of > or = 0.5 U/ml was considered protective for rabies virus. RESULTS: Significant changes were not detected in CDV, CPV, and rabies virus titers following chemotherapy in tumor-bearing dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that established immunity to CDV, CPV, and rabies virus from previous vaccination is not significantly compromised by standard chemotherapy used to treat tumor-bearing dogs.

Animals↗

Nucleotide sequence analysis of the large (L) genes of phocine distemper virus and canine distemper virus (corrected sequence).

This paper corrects the previously published sequence of the L gene of canine distemper virus (CDV). Errors in the published sequence (M. S. Sidhu et al., 1993, Virology 193, 50-65) led to frame shifts between residues 1021-1032, 1190-1219 and 1645-1650; a deletion of 21 amino acids between residues 1684-1705, and a single residue deletion at residue 1478. Residue 237 is now found to be glycine rather than tryptophan and residue 1626 proline instead of threonine. The sequence of the L gene of phocine distemper virus (PDV) was also determined. Alignment of the morbillivirus L proteins showed that PDV and CDV are more closely related to each other than to rinderpest virus and measles virus. Two regions of low identity are proposed to function as hinge regions between three highly conserved domains (I-III) in the morbillivirus L proteins. New sequence motifs have been identified on the basis of conservation in the morbilliviruses and the Paramyxovirinae.

Amino Acid Sequence↗

Biological properties of phocine distemper virus and canine distemper virus.

Morbilliviruses constitute a major threat to the health of animal and man. To date the Morbillivirus genus in the Paramyxoviridae family comprises five established members, namely canine distemper virus (CDV), phocine distemper virus (PDV), measles virus (MV), rinderpest virus (RPV), and peste-des-petits-ruminants virus (PPRV). In addition, morbillivirus candidates infecting aquatic mammals were recently discovered. The present review on the biology of morbilliviruses focuses on knowledge gained by our group in studies on PDV and CDV. The aims of these studies were: i) to investigate the biological properties of the recently recognized PDV, which was found to be the primary etiology of epidemics with high mortality in seals in Western Europe, ii) to extend our knowledge of the biological properties of CDV. The morbillivirus particle is enveloped. The helical nucleocapsid core contains a single-stranded, non-segmented RNA genome of negative sense of 15 to 16 kilobases in length. The genome is organized in six transcriptional units or genes. Overall, the studies of the genome of PDV revealed a genetic map principally fitting with that determined for other morbilliviruses. The nucleotide and deduced amino acid sequences have been determined for five PDV genes named in analogy with the encoded structural proteins of other morbilliviruses in the order: 3'N(1683)-P(1644)-M(1443)-F(2206)-H(1952)-L5' (The figures in brackets denote nucleotide lengths of the genes of the Danish PDV isolate). The L gene (covering approximately 8900 nucleotides) remains to be sequenced. The six genes are likely to code for at least eight distinct proteins. The nucleocapsid (N) protein was found to consist of 523 amino acids in PDV. The following gene of the transcription map encoded the P protein of 507 amino acid residues. Similar to other morbilliviruses, the P gene of PDV was shown to have additional coding capacity for two distinct proteins V (299 amino acids) and C (174 amino acids). The results presented provide evidence for editing at transcript of the PDV P gene by insertion of nontemplated G residues at a specific site. The edited version of the mRNA was found to encode the cystein-rich V protein. The three envelope-associated proteins of PDV were predicted to consist of 335 (M), 537 (F0) and 607 (H) amino acid residues. The nucleotide and deduced amino acid sequences of the N, P, M, F, and H genes of PDV were aligned with corresponding sequences of other established members of the genus Morbillivirus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A study of measles virus and canine distemper virus antibodies, and of childhood infections in multiple sclerosis patients and controls.

We investigated the levels of neutralizing antibodies to measles virus and canine distemper virus (CDV) in 72 multiple sclerosis patients (MS) and matched controls and also examined the frequency and age of onset of a number of childhood illnesses, including measles. The frequency of each childhood illness was not significantly different between cases and controls, but cases did report a later age at measles infection. Our data suggest that the risk of MS is increased by a factor of 1.9 if measles infection occurs between 5 and 9 years of age. A validity survey, based on a questionnaire to general practitioners, suggested substantial inaccuracy in the patients' reports of when they had measles, but the direction and degree of inaccuracy did not appear to be different between cases and controls. We also found higher titres of neutralizing antibodies in cases than controls to both measles virus and CDV, although the CDV difference was not statistically significant. In the light of a significant correlation between measles and CDV titres in both cases and controls, we used paired logistic regression to determine if the case-control difference in titres for each virus could be explained by a confounding effect on one by the other. The numbers were too small, however, to enable us to separate out any independent association of either virus with MS.

Age Factors↗

Matrix genes of measles virus and canine distemper virus: cloning, nucleotide sequences, and deduced amino acid sequences.

The nucleotide sequences encoding the matrix (M) proteins of measles virus (MV) and canine distemper virus (CDV) were determined from cDNA clones containing these genes in their entirety. In both cases, single open reading frames specifying basic proteins of 335 amino acid residues were predicted from the nucleotide sequences. Both viral messages were composed of approximately 1,450 nucleotides and contained 400 nucleotides of presumptive noncoding sequences at their respective 3' ends. MV and CDV M-protein-coding regions were 67% homologous at the nucleotide level and 76% homologous at the amino acid level. Only chance homology was observed in the 400-nucleotide trailer sequences. Comparisons of the M protein sequences of MV and CDV with the sequence reported for Sendai virus (B. M. Blumberg, K. Rose, M. G. Simona, L. Roux, C. Giorgi, and D. Kolakofsky, J. Virol. 52:656-663; Y. Hidaka, T. Kanda, K. Iwasaki, A. Nomoto, T. Shioda, and H. Shibuta, Nucleic Acids Res. 12:7965-7973) indicated the greatest homology among these M proteins in the carboxyterminal third of the molecule. Secondary-structure analyses of this shared region indicated a structurally conserved, hydrophobic sequence which possibly interacted with the lipid bilayer.

Amino Acid Sequence↗

Downregulation of endothelin receptor mRNA synthesis in C6 rat astrocytoma cells by persistent measles virus and canine distemper virus infections.

Persistent infections of C6 rat astrocytoma cells with measles (subacute sclerosing panencephalitis [SSPE]) virus (C6/SSPE cells) or canine distemper virus (C6/CDV cells) cause a loss of endothelin-1 (ET-1) binding to its specific receptors (ETRA type) and subsequent ET-1-induced Ca2+ signaling. It was the aim of this study to investigate the underlying mechanism of this phenomenon in more detail. By using an RNase protection assay, it was found that ETRA mRNA disappears, whereas other cellular mRNA species, e.g., beta-actin mRNA, were not influenced. The data show that the loss of the ET-1 signaling pathway in C6/SSPE and C6/CDV cells is due to a receptor downregulation at the transcriptional level.

Animals↗

Examination of the immunological relationship between measles virus and canine distemper virus using monospecific measles antisera.

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 haemagglutinin (anti-HA), the haemolysin (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 haemolysin 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 on the other hand, totally removed all measles and CDV-specific HA and RNP activity. CDV was not neutralised by any of the monospecific antisera when tested either as individual antisera or as mixtures. Our results demonstrate the occurrence of antigenic variation between different strains of CDV, they also reveal unique antigenic determinants in both measles virus and CDV.

Antigens, Viral↗

Response of gray foxes to modified live-virus canine distemper vaccines.

Ten gray foxes seronegative for canine distemper virus were vaccinated with 1 of 3 commercial modified live-virus canine distemper vaccines. Of 5 foxes receiving vaccine A (chicken tissue culture origin), 4 developed significant titers (greater than or equal to 1:100) of neutralizing antibody to canine distemper virus and remained clinically normal after vaccination. Two of 3 foxes vaccinated with vaccine B (canine cell line origin) and both foxes receiving vaccine C (canine cell line origin) died of vaccine-induced distemper. Five unvaccinated control foxes died of distemper after a known occasion for contact transmission of virus from a fox vaccinated with vaccine B. The results suggested that the chicken tissue culture origin modified live-virus canine distemper vaccine is probably safe for normal adult gray foxes, whereas the canine cell origin vaccines are hazardous. The results of this study tended to corroborate anecdotal experiences of veterinarians who have observed that gray foxes frequently die from distemper soon after vaccination with modified live-virus canine distemper vaccines.

Animals↗

Measles virus and canine distemper virus target proteins into a TAP-independent MHC class I-restricted antigen-processing pathway.

After infection of CEM174.T2 cells [deficient for the transporter of antigen presentation (TAP)] with measles virus (MV) the nucleocapsid protein is recognized by L(d)-restricted cytotoxic T cells in a TAP-independent, chloroquine-sensitive fashion. Presentation via the TAP-independent pathway requires virus replication. During MV infection of the cell the nucleocapsid as well as the matrix protein enter the endolysosomal compartment as indicated by colocalization with the lysosomal-associated membrane protein 1 (LAMP-1). Similarly, the nucleocapsid protein of canine distemper virus (CDV) is recognized in a TAP-independent fashion. In addition, a recombinant MV expressing bacterial beta-galactosidase protein is able to introduce the recombinant antigen into the TAP-independent pathway whereas a vaccinia virus expressing beta-galactosidase is not. These data and a report about TAP-independent recognition of parainfluenza virus type 1 suggest that members of the Paramyxoviridae family regularly introduce viral proteins into the TAP-independent antigen-processing pathway.

Animals↗

Antibody responses to measles virus and canine distemper virus in multiple sclerosis.

Age-matched serum and cerebrospinal fluid from 20 multiple sclerosis patients and 20 control patients with other neurological diseases were examined for antibodies to radiolabeled measles virus and canine distemper virus using an immunoprecipitation polyacrylamide gel technique. No evidence for reactivity to unique canine distemper virus-virion polypeptides in the multiple sclerosis group was obtained. Competitive binding experiments with cerebrospinal fluid using labeled and unlabeled viral antigens failed to detect preferences in binding of antibodies for canine distemper virus versus measles virus. Cerebrospinal fluid samples tested for antiviral immunoglobulin M activity using both measles and canine distemper viruses showed no activity. The results of this study failed to implicate canine distemper virus directly as a cause of multiple sclerosis.

Antibody Formation↗

The role of the 5' nontranslated regions of the fusion protein mRNAs of canine distemper virus and rinderpest virus.

The mRNAs which code for the fusion proteins of the morbilliviruses (measles virus, canine distemper virus, and rinderpest virus) have unusually long 5' untranslated regions (UTRs) which are GC-rich and are capable of folding into extensive secondary structures. In measles virus the first AUG codons in the fusion (F) protein mRNA are in close proximity at nucleotide positions 574 and 583 and protein translation is initiated at the second position. In the canine distemper virus (CDV) and rinderpest virus (RPV) F gene transcripts the analogous initiation codons are preceded by several other AUG codons many nucleotides upstream either in the same reading frame or at the beginning of other short open reading frames. We have studied the effect of deleting these upstream regions on the production of the fusion proteins of both CDV and RPV from cDNA constructs. Within the cells the presence of these regions enhances the production of the F protein while, in contrast, the production of the authentic F protein from in vitro translations using RNA transcripts is inhibited by these sequences.

Animals↗

Interleukin-1beta, -6, -12 and tumor necrosis factor-alpha expression in brains of dogs with canine distemper virus infection.

Canine distemper virus infection in dogs is commonly associated with demyelinating central nervous system lesions. Investigations on viral protein expression by studying mRNA and protein distribution together with the characterization of CD4 and CD8 inflammatory cells and MHC class II up-regulation revealed a biphasic disease process. To further investigate the cellular interactions in the different plaque types the cerebella of 14 dogs with confirmed distemper infection were investigated for expression of interleukin (IL)-1beta, -6, -12 and tumor necrosis factor-alpha (TNF) by immunohistochemistry using rabbit polyclonal anti-cytokine antibodies. T-cells and astrocytes were identified with rabbit anti CD3- and GFAP-monoclonal and polyclonal antibodies, respectively; and microglia/macrophages were characterized by their ability to bind lectin from Bandeiraea simplicifolia (BS-1). To further name the cytokine expressing cells immunoenzymatic double staining using DAB and New Fuchsin was performed. White matter lesions were classified according to histopathological criteria into acute, subacute and chronic. Canine distemper virus nucleoprotein antigen was demonstrated in nearly all plaques, except in older plaques where virus was not present within the plaque but adjacent to the lesion. IL-1 expression was observed to varying degrees in all types of lesions. Most often IL-1 was present in CD3 and BS-1 positive cells in the brain parenchyma in earlier plaques and comprising perivascular cuffs found in chronic plaques. IL-6 expression was present in all lesions, and followed a similar distribution pattern as IL-1. IL-12 displayed very often a granular extracellular pattern of immunoreactivity, especially in the brain parenchyma, and was found only in individual perivascular cells. TNF staining, predominantly found in astrocytes, was present in lesions of various types; however, staining appeared to be stronger in acute lesions and decreased in chronic plaques. In the latter, TNF seemed to be more prominent in areas adjacent to the plaques. Summarizing, in early non-demyelinating lesions without overt inflammation TNF seemed to be important, whereas in distemper lesions with inflammatory infiltrates IL-1 and to a lesser degree IL-6 were more prominent. These results imply that TNF may be involved in the pathogenesis of early demyelination in nervous distemper.

Animals↗