SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
The gross and microscopic pathology of phocine distemper is described. The most striking features were pulmonary congestion and emphysema associated with proliferation of type II pneumocytes, often forming syncytia. Secondary bacterial infection was common and associated with marked atrophy of lymphoid tissues and degenerative changes in the mucosa of the airways.
The death of many seals believed to be infected with phocine distemper virus was found to be associated with a variety of mainly opportunistic bacterial pathogens. The bacteria most frequently involved were Bordetella bronchiseptica, Corynebacterium species and a variety of Streptococci. Seals dying on different parts of the coast of Britain were infected with these organisms in differing proportions.
This paper uses simple mathematical models to examine the long-term dynamic consequences of the 1988 epizootic of phocine distemper virus (PDV) infection in Northern European common seal populations. In a preliminary analysis of single outbreaks of infection deterministic compartmental models are used to estimate feasible ranges for the transmission rate of the infection and the level of disease-induced mortality. These results also indicate that the level of transmission in 1988 was probably sufficient to eradicate the infection throughout the Northern European common seal populations by the end of the first outbreak. An analysis of longer-term infection dynamics, which takes account of the density-dependent recovery of seal population levels, corroborates this finding. It also indicates that a reintroduction of the virus would be unlikely to cause an outbreak on the scale of the 1988 epizootic until the seal population had recovered for at least 10 years. The general ecological implications of these results are discussed.
The 'time, place, individual' approach, widely used in characterising human epidemics, was applied to the 1988 phocine distemper virus (PDV) epizootic affecting North Sea seals. Estimates of time of death from 157 (69%) of the 228 dead seals necropsied in 1988 indicated that the number of carcasses which were found more than 14 days post mortem increased as the epizootic progressed. Although information provided by epizootic curves based on when and where carcasses were reported are affected by the accuracy of such data, the PDV epizootic curves were characteristic of a propagative epidemic. The individual characteristics of the carcasses provided more useful information. 1. Common seals were more susceptible than grey seals. 2. Males and older seals had a greater exposure to the virus than females and younger animals. 3. The likelihood of viral transmission was greater on land. Seasonal, sex and age related variation in haul-out behaviour affected transmission probabilities and rates. 4. The risk of infection for a susceptible individual during August was higher for seals in England and Northern Ireland than for those in Scotland. These findings illustrate the importance of population characteristics including behaviour and social organisation in determining the pattern and spread of wildlife epizootics.
Changes in abundance at haul-out sites were followed, and data on the number of deaths collected, to describe the pattern and extent of mortality resulting from the 1988 phocine distemper virus outbreak in the Moray Firth common seal population. Mortality in this population was estimated to be between 10% and 20%, and was low in comparison to some other parts of the North Sea. Most deaths occurred in the 3-month period from 1st August 1988, and there was no sign of a resurgence of the disease during the 1989 breeding season or moult.
Sera from seals infected during the 1988 European epizootic of phocine distemper virus and sera from Canadian seals collected since 1972 have been tested for the presence of antibodies to morbillivirus. Approximately one third of the Canadian sera have been shown to contain anti-morbillivirus antibodies; the possibility that these populations of seals provided a source of infection for European seals is discussed.
Blood samples collected from live common seals (Phoca vitulina) and grey seals (Halichoerus grypus) around the coast of Scotland and Northern Ireland during, and immediately after, an epizootic caused by phocid distemper virus (PDV) were analysed for thymulin content. Thymulin levels were compared with neutralization titres and concentrations of organochlorine contaminants (DDT and its metabolites, seven chlorinated biphenyl congeners) derived from blood and blubber samples collected from the same animals and analysed independently. Thymulin levels in grey seals (mean 2827 +/- 1355 fg/ml) were negatively correlated with the logarithm of virus neutralization titre. In common seals they varied significantly between age classes. There was no direct relationship between thymulin levels and contaminant levels in either species. However, when an estimate of time since exposure was included in the regression analysis for common seals, there was a highly significant relationship between thymulin and the two chlorinated biphenyl congeners with the highest concentrations in blubber.
We compared concentrations of organochlorines in the blubber of common seals (Phoca vitulina) found dead during the 1988 phocine distemper epizootic with levels in animals which survived it. There were highly significant differences between the live and dead animals, and between sample sites. These were not fully accounted for by seasonal and condition-related changes in blubber thickness.
Cerebrospinal fluid (CSF) form nine lethally infected and three convalescent gnotobiotic dogs infected with the R252 strain of canine distemper virus (CDV) was evaluated prior to and following infection. Lethally infected dogs had a mean seven-fold increase in CSF albumin concentration compared to the preinoculation value, not present in dogs destined to survive. Immunochemical examination of tissue from these dogs revealed prominent perivascular localization of albumin. Examination of CSF cells demonstrated mild leukocytosis in both groups at the time when encephalopathic deaths occurred, with decreased lymphocyte percentages, particularly Thy-1-bearing lymphocytes, in lethally infected dogs. These dogs also had more extensive expression of viral antigens in CSF and peripheral blood leukocytes at the time of death than did surviving dogs, and failed to make antibody to viral antigens. The findings link terminal breakdown of the blood-brain barrier and extensive viral antigen expression in CSF leukocytes with experimental CDV infection resulting in death.
We have previously shown that, in experimentally inoculated mice, canine distemper virus (CDV), a neurotropic virus, selectively infects certain brain structures (hypothalamus, hippocampus, monoaminergic nuclei, etc). Here we demonstrate that tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 transcripts are selectively expressed in these CDV-targeted structures, except in the dentate gyrus, where cytokines are induced without prior CDV replication. The time-course of TNF-alpha expression vs. viral replication in the hypothalamus was different from that in hippocampus. In addition, we show that a substantial number of neurons express TNF-alpha and IL-6. These findings provide new insights into the possible participation of cytokines in the neurological disorders triggered by CDV infection.
The R252 neurotropic isolate of canine distemper virus (CDV) produces cytopathic effects (CPE) dominated by strand formation rather than by the formation of multinucleate giant cells. The lack of well-defined CPE and consequent rapid spread of infection throughout the cell monolayer has hindered plaque purification of this virus by conventional methods. However, the use of an immunological detection system which utilizes binding of hyperimmune dog serum to virus-infected cells, followed by the identification of those sites by staphylococcal Protein A-coupled sheep red blood cells (reverse passive haemadsorption) allowed infected foci in cell monolayers to be detected as early as 4 days after infection, coincident with the appearance of the first immunofluorescently identified viral foci. Foci of haemadsorption were specific to sites of CDV infection as demonstrated by blocking experiments. Material recovered from the plaques was successful in infecting Vero cells. Thus, immunologically mediated adsorption of Protein A coupled red blood cells can be used to identify and isolate foci of viral infection which exhibit minimal or no viral CPE without destroying viral replicative ability.
A cDNA library was prepared from canine distemper viral (CDV) messenger RNA (mRNA) derived from Vero cells lytically infected with the Onderstepoort strain (Ond) of CDV. A 300 base pair insert was identified which, by Northern blot analysis and Sanger sequence data, was shown to be specific to the nucleocapsid gene. The nucleocapsid (NC) clone was radiolabelled with 32P using nick translation and used to detect viral RNA in both dot-blot and in situ preparations of Vero cells lytically infected with Onderstepoort CDV (Ond-CDV) and immortalized mink lung cells persistently infected with racoon origin CDV (CCL64-RCDV). Dot-blot hybridization results paralleled immunofluorescent results in the lytically infected cells. In 18 persistently infected cell lines from the RCDV-CCL64 parental stock, 13 lines were positive and two were negative on both immunofluorescence and dot-blot hybridization analysis for CDV antigen and RNA, respectively. Viral nucleic acid was detected in these persistently infected cells, where as few as 1.9% of the members of a line were positive on immunofluorescence. A dot-blot autoradiographic signal was obtained in three lines which were negative for CDV antigen. CDV RNA was detected in both lytically and persistently infected cell lines by in situ hybridization, where decreasing probe length was important in increasing the sensitivity of this assay. Viral RNA was detected in over 90% of the lytically infected cells, where only 70% were positive for viral antigen by immunofluorescence.
The nucleotide sequence of the gene encoding the fusion protein of canine distemper virus was determined from cDNA clones derived from virus genome RNA and poly(A)+ RNA extracted from infected cells. The mRNA encoding the F protein is about 2300 nucleotides in length including the 3' poly(A) tail. There is a large open reading frame from nucleotides 86 to 2071 which begins at the first AUG codon in the F mRNA. This reading frame encodes a protein of 662 amino acid residues with a calculated mol. wt. of 73001. The first major hydrophobic domain in the amino acid sequence of the deduced protein (residues 104 to 130) may represent all or part of a signal sequence for cleavage of the N terminal part of the F2 protein. There are four potential N glycosylation sites in the F protein located within the F2 part of the molecule or the putative signal sequence, and one in the F1 portion. A second hydrophobic region corresponds to the proteolytic cleavage site which generates the F2 and F1 subunits. This stretches from residue 225 to 262 and the N terminal part of the F1 protein shows sequence conservation with the other paramyxoviruses. A third major hydrophobic domain near the C terminus of the F protein probably represents the membrane anchor for the F protein (residues 602 to 630). The F1 proteins of six paramyxoviruses are compared and shown to have substantial conservation of those residues important in the maintenance of tertiary structure of this protein.
The nucleotide sequence of the gene coding for the attachment protein of the Convac strain of the canine distemper virus (CDV), corresponding to the haemagglutinin (H) gene of measles virus was determined using a mRNA-derived cDNA clone and genomic viral RNA. The mRNA transcribed from the CDV H gene is 1944 nucleotides long excluding the polyadenylated tail. Only one long open reading frame was found comprising nucleotides 21-1841. The predicted protein has a single hydrophobic region which can serve as a membrane anchoring domain. The deduced 607 amino acids would code for a protein of 68,247 Da, to be compared with an approximate protein molecular weight in SDS-PAGE of the glycosylated protein, which is 85,000 Da. The CDV H protein exhibited seven potential N-linked glycosylation sites. These were concentrated to the carboxyterminal part of the CDV H protein and differed markedly from measles virus (MV) and rinderpest virus (RPV) where the potential sites were mostly conserved and located in the amino-terminal half of the proteins. In spite of the differences in amino acid composition of these three H proteins their hydrophilicity/hydrophobicity plots were closely similar with the major hydrophobic region at an identical location. All the 12 cysteine residues found in the CDV H protein were conserved in MV and RPV. The amino acid homology between CDV and MV H protein was 37% and between CDV and RPV H protein 38%. The fact that the corresponding homology between the MV and RPV proteins is almost 60% shows that the evolutionary separation between CDV and RPV occurred at a much earlier time than the separation between RPV and MV.
Canine distemper virus (CDV) causes an encephalomyelitis in dogs which varies with the viral strain. The CDV Cornell A75-17 strain produces a delayed, subacute to chronic, demyelinating CNS disease. In contrast, the Snyder Hill (CDV-SH) strain-associated neurological disease is more acute in onset, is usually non-demyelinating and primarily produces lesions in the gray matter. In these studies we describe the effects of these two virulent and one avirulent CDV strain, Rockborn (CDV-RO), on astrocytes in dissociated canine brain cell cultures. In multiple replicate experiments, astrocytes were infected most rapidly by CDV-RO [100% of astrocytes were infected by 14 days post-inoculation (p.i.)]. This strain caused severe cytopathic effect (CPE) and cytolysis. CDV-SH similarly produced a rapid infection of the astrocytes. In contrast, CDV A75-17 infected less than 25% of the astrocyte population during the first 28 days p.i. (+/- 7 days); after 28 days p.i., a rapid rise in astrocyte infection occurred. Both virulent viruses caused astrocytic syncytial formation but did not cause cytolysis of the astrocyte population as was observed with the attenuated virus. Titers of infectious virus, released into the supernatant fluid, reflected the degree of astrocyte infection. Virus released by the cultures late in CDV A75-17 infection showed enhanced ability to infect newly derived astrocytes; in contrast, brain cell passaged CDV-SH did not show increased growth in these cells. These results show that (1) there is a difference in growth rate, CPE and capacity for adaptation of three different CDV strains in astrocytes in vitro, and (2) some aspects of the disease (such as persistence in white matter) produced by the virulent strains in vivo may be related to the course of astrocyte infection observed in vitro.
The technique of in situ hybridisation was applied using radioactively labelled riboprobes to examine for the presence of canine distemper (CDV) and measles (MV) RNA in Paget's disease of bone. The results indicate that in 41% of Paget's patients, CDV RNA could be detected in osteoclasts, osteoblasts, and osteocytes, but not in controls. In contrast, RNA to the measles virus was not detected. We suggest that CDV may in some cases play a role in the aetiology of Paget's disease.
We have previously shown that the canine paramyxovirus, canine distemper virus (CDV), is a possible aetiologic agent in Paget's disease of bone and in the canine bone disorder, metaphyseal osteopathy. More recently, we have examined the effects of CDV on the formation of multinucleated, tartrate resistant acid phosphatase positive, calcitonin receptor positive, osteoclast-like cells in cultures of canine bone marrow mononuclear cells, and shown that both in vitro and in vivo infection with CDV produced a dose dependent increase in the number and size of osteoclast-like cells. We have now extended these results to show that CDV infection induces interleukin-6 and c-Fos mRNA in these cells, similar to our recent findings in pagetic bone cells. These results further support the hypothesis that CDV might be involved in the aetiopathogenesis of Paget's disease and metaphyseal osteopathy and suggest that canine marrow culture systems will prove useful as an in vitro model to examine the disease processes in more detail.
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.