Canine Distemper Virus Infection Research Articles

Immunological and pathological findings in demyelinating encephalitis associated with canine distemper virus infection.

Nine dogs with canine distemper encephalitis (CDE) were examined with immunological techniques including demonstration of antibodies against canine distemper virus (CDV) in the serum and against myelin basic protein (MBP) in serum and in CSF. Mitogen stimulation tests of lymphocytes were also done. The brains were examined pathologically and immunoglobulin and C3 were demonstrated in lesions by means of immunohistological techniques. Six dogs with acute CDE had none or low antibody levels against CDV or MBP, and there was no immunoglobulin in demyelinating lesions. Some of these dogs had depressed lymphocyte mitogen responses. Two dogs with chronic CDE showed recovery of lymphocyte mitogen responses. One of these had a significant antibody response against CDV and MBP in the serum. Both dogs with chronic CDE had very high antibody titers against MBP in the CSF and demyelinating lesions contained immunoglobulin. These results suggest that acute demyelination in CDE is probably due to some direct viral activity and that the progression of demyelination in chronic CDE is associated with a local immune response.

Canine distemper virus infection of weanling mice: Pathogenesis of CNS disease

Intracerebral inoculation of canine distemper virus (CDV) into weanling BALB/c, ICR and SJL mice produced acute encephalitis 2–3 weeks later. All animals that became ill exhibited lethargy and hind-limb paralysis followed by death. BALB/c mice were more susceptible to CDV than ICR or SJL mice. Pathologic changes were characterized primarily by meningitis and focal areas of parenchymal inflammation, necrosis and microglial hypertrophy. CDV was readily isolated from infected mouse brain 10–23 days after infection, and peak virus titers occurred at the height of neurologic disease 14–17 days after infection. CDV antigen was detected by immunofluorescence throughout grey and white matter of the brain and brain stem. CDV was rescued from explanted mouse brain tissue after it could not be isolated from brain homogenates. BALB/c mice which were inoculated intracerebrally with CDV one month after initial virus injection developed meningitis and a non-inflammatory degeneration of white matter.

SEARCH FOR CANINE-DISTEMPER-VIRUS ANTIBODIES IN MULTIPLE SCLEROSIS: A Detailed Virological Evaluation

Sera and cerebrospinal fluid samples from multiple-sclerosis (MS) patients, matched controls, and subacute sclerosing panencephalitis (SSPE) patients were analysed for the presence of antibodies specific for measles and canine distemper virus (CDV). Virus-specific antibodies were identified by hæmagglutination inhibition, neutralisation, and immune precipitation in combination with polyacrylamide-gel electrophoresis. SSPE and MS patients had a higher antibody activity towards measles virus than controls. Moreover, human sera partly neutralised CDV; this was attributed to antibody activity against CDV proteins, antigenically related to those of measles virus. However, CDV-specific antibodies were not found in the samples tested. These findings indicate that MS can develop without a preceding CDV infection.

Induction of chronic neurologic disease in mice with canine distemper virus.

The capacity of a mouse-adapted strain of canine distemper virus (CDV) to induce central nervous system (CNS) disease in weanling mice was investigated. Lethality of infection was found to be mouse-strain-dependent. In sensitive strains, an acute meningoencephalomyelitis developed. Brain tissue from acutely ill animals demonstrated numerous foci of viral antigen, and extracts yielded infectious virus. Mice of resistant strains, notably the SJL strain, survived the effects of acute infection, appeared well for several weeks, and then began to develop signs of subacute CNS disease. Preliminary histopathologic examination of brain and cord from acutely ill animals revealed prominent perivascular mononuclear cell infiltrates, mononuclear cell meningitis, and gliosis. These features were also found in the subacute disease, where, however, the lesions were less severe. Also, in the latter, virus antigen could not be demonstrated. The results indicate that CDV infection of mice may provide a promising model system for the study of virus-induced chronic CNS disease.

Polioencephalomalacia associated with canine distemper virus infection.

Eight dogs with severe neurologic signs, including seizures, had polioencephalomalacia of the pyriform cortex, Ammon's horn and deep structures in the temporal lobe. The polioencephalomalacia was considered to be a consequence of canine distemper virus infection based on clinical signs, typical inclusions, the demonstration of viral antigens in the lesions and of characteristic paramyxovirus nucleocapsids by electron microscopy. Little evidence for neuronal destruction by direct viral activity was found. Selective nerve cell necrosis was attributed to ischemia (vascular lesions and seizure induced consumptive anoxia) and immune mechanisms. The selective involvement of the rhinencephalic structures was thought to be related to the mode of entry and spread of the virus.

Syncytia inhibition by immune lymphocytes: in vitro test for immunity to canine distemper.

A simple and rapid (24-h) assay for peripheral blood lymphocyte-associated immunity to canine distemper virus (CDV) is described. The test is based upon leukocyte-associated inhibition of CDV-induced syncytia formation in Vero cells. The technique quantitates the response morphologically, thereby eliminating the requirement for release of radiolabeled compounds. Positive results were determined from specific-pathogen-free and gnotobiotic dogs exposed to CDV via hyperimmunization, vaccination with a modified live virus vaccine, and after virulent virus infection. Preinoculation lymphocytes and lymphocytes from non-immune dogs did not inhibit CDV-induced syncytia formation. Maximum responses were observed 7 to 21 days after initial exposure and declined thereafter. The method can be used to further investigate the role of immune lymphocytes in the recovery from CDV infection.

Observations on the distribution of canine distemper virus in the central nervous system of dogs with demyelinating encephalitis

The distribution of canine distemper virus in the central nervous system was examined in 11 dogs with demyelinating encephalitis by the direct fluorescent antibody technique on paraffin sections of brain and spinal cord. In the grey matter there was a good correlation between the presence and severity of lesions and presence and amount of viral antigen. Large concentrations of virus were found in neurons and their processes. In most demyelinating lesions only small amounts of viral antigen were found, mostly located in astrocytes. The potential importance of the role of the astrocyte in demyelination in canine distemper virus infection is stressed.

A canine distemper model of virus-induced anergy.

For development of an animal model of virus-induced anergy, the effect of canine distemper virus (CDV) upon cell-mediated immunity in dogs was investigated. First, canine cutaneous reactions and in vitro lymphocyte responses to soluble protein antigens were characterized. Dogs immunized with picryl guinea pig albumin and with keyhole limpet hemocyanin (both in complete Freund's adjuvant) responded reproducibly to intracutaneous challenge with these antigens. Reactivity peaked in 20-40 days (maximal induration, 6-50 mm). Lymphocytes from these animals responded in vitro to stimulation with keyhole limpet hemocyanin or purified protein derivative. This stimulation was antigen-specific and was maximal on day 6 of culture. Infection with CDV depressed cutaneous reactivity and lymphocyte response in vitro to antigens and mitogens. This effect was transient in animals previously vaccinated with attenuated CDV; however, gnotobiotic puppies (susceptible to CDV) had prolonged depression of cell-mediated immunity and lymphopenia. Some of these animals developed neurologic symptoms and died. The findings indicate that CDV infection is a potentially useful model for study of virus-induced depression of T (thymus)-cell responses and support the hypothesis that there is more than one mechanism responsible for this phenomenon.

Effects of canine distemper virus infection on lymphoid function in vitro and in vivo.

In the present study, the immunodepressive effects of canine distemper virus (CDV) infection of dogs on two parameters of lymphocyte function, namely phytomitogen-induced cellular proliferation and skin allograft rejection, were investigated. Infection of susceptible gnotobiotic dogs with virulent R252-CDV resulted in a depression of peripheral blood lymphocyte mitogen response as measured by (3H)thymidine incorporation for up to 10 weeks after inoculation. This effect coincided with the appearance of viral antigen by immunofluorescence in leukocytes but persisted after the virus was no longer detectable. Loss of mitogen reactivity was seen in all infected dogs. However, when these same CDV-infected dogs were challenged with foreign skin allografts, no significant retention of grafts over controls was observed despite the depressed lymphocyte activity. Considering the in vitro and in vivo data it was concluded that, although immunodepressive effects of CDV were demonstrated in vitro, paralled in vivo experiments indicated that less than complete suppression of immune functions occurs during the course of CDV infection.

Epizootic of canine distemper virus infection among urban raccoons and gray foxes.

An epizootic of canine distemper (CD) virus infection is described among raccoons and gray foxes in urban Sarasota County, Florida. The epizootic persisted for 2 years with a total of 114 raccoons and 8 gray foxes being handled by Sarasota County Animal Control. Virus was isolated from clinically ill raccoons on two separate occasions, 7 months apart. CD antibodies were detected in 54.5% of a sample comprising both clinically ill and apparently normal raccoons. The incidence of CD in dogs in the county did not increase during the 2 year period.

Myelin-specific autoantibodies associated with central nervous system demyelination in canine distemper virus infection.

Sera from dogs with spontaneously occurring and experimentally produced canine distemper virus-associated demyelinating encephalitis were examined for antibodies to central nervous system myelin by the complement fixation and indirect immunofluorescent methods. Complement-fixing immunoglobulin M antibodies and non-complement-fixing immunoglobulin G antibodies were found in 97% of the spontaneous cases. In comparison, only 28% of control sera contained these antibodies; furthermore, mean antibody titers in the control groups were significantly lower (P < 0.005) when compared to the distemper group. Complement-fixing antimyelin antibodies were also demonstrated in gnotobiotic dogs with experimentally induced distemper virus-associated demyelination. The antibody response could be correlated with clinicopathological features of the disease produced. Results of this study indicate that demyelination in canine distemper may proceed by immune mechanisms.

Ultrastructural features of canine distemper virus infection in a dog kidney cell line.

SUMMARY Cultures of dog kidney cells were infected with canine distemper virus at an input multiplicity of 1.9 and the subsequent events followed by electron microscopy, conventional staining methods and virus titration. Maturation and release of virus commenced within 24 hr of infection and was a slow but prolonged process, the infected cell producing small amounts of virus for at least 48 hr. After formation in cytoplasmic foci, often perinuclear, the virus nucleocapsid migrated to the cell membrane, below which it adopted a symmetrical configuration, the cell membrane at the same time acquiring a layer of fine surface projections. Maturation of virus then occurred by a protrusion and pinching off of these areas. Cytoplasmic aggregates of nucleocapsid were not detected by light microscopy. The characteristic phloxinophilic cytoplasmic inclusions, which appeared between 24 and 48 hr after infection, did not stain with acridine orange. Some consisted of a mass of amorphous electron-dense material and others of nucleocapsid-like filaments enmeshed in an electron-dense matrix but all contained a number of pockets in which membrane-bound vacuoles and tubules were prominent.

Ultrastructural features of canine distemper virus infection of the chorioallantoic membrane of the hen's egg.

SUMMARY The chick embryo chorio-allantoic membrane was examined 6 days after inoculation of the ondestepoort strain of canine distemper virus. Multinucleated cells containing cytoplasmic inclusions were observed in the chorionic epithelium. These inclusions consisted of randomly arranged nucleocapsid filaments. The filaments had an outer lightly staining layer of radial fibrils in addition to their dense core. Budding and mature virus particles were observed less frequently. The morphological stages of distemper virus replication resembled those reported for measles and rinderpest viruses in other systems.

Subclinical infection of dogs by canine-adapted measles virus evidenced by their subsequent immunity to canine distemper virus.

Moura, Roberto A. (Chas. Pfizer and Company, Inc., Terre Haute, Ind.) and Joel Warren. Subclinical infection of dogs by canine-adapted measles virus evidenced by their subsequent immunity to canine distemper virus. J. Bacteriol. 82:702-705. 1961.-Young dogs were inoculated with virulent measles virus which had been adapted to canine kidney or human amnion cell culture. None of the animals showed any clinical symptoms nor could virus be isolated from the blood, although measles-neutralizing and complement-fixing antibodies developed during convalescence. All dogs failed to develop antibody to canine distemper. However, when these and normal control animals were subsequently inoculated intracerebrally with virulent distemper virus, each of the controls succumbed to typical symptoms, whereas all of the measles-immune dogs survived. These results suggest that the cross-protection conferred by measles against canine distemper virus infection involves factors other than humoral antibody. The immunity persists for a considerable length of time.

Fat metabolism in three forms of experimental obesity. IV. Instantaneous rates of lipogenesis in vivo.

Fat metabolism in three forms of experimental obesity. IV. Instantaneous rates of lipogenesis in vivo.

Fat metabolism in three forms of experimental obesity; acetate incorporation.

Fat metabolism in three forms of experimental obesity; acetate incorporation.