Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The GDVII strain and other members of the GDVII subgroup of Theiler's murine encephalomyelitis viruses (TMEV) cause an acute lethal neuronal infection in mice, whereas the DA strain and other members of the TO subgroup of TMEV cause a chronic demyelinating disease associated with a persistent virus infection. We used GDVII/DA chimeric infectious cDNAs to produce intratypic recombinant viruses in order to clarify reasons for the TMEV subgroup-specific difference in demyelinating activity. We found that both the GDVII and DA strains contain a genetic determinant(s) for demyelinating activity. No demyelination occurs following GDVII strain inoculation because this strain produces an early neuronal disease that kills mice before white matter disease and persistent infection can occur.
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PMID:Strains from both Theiler's virus subgroups encode a determinant for demyelination. 224 99

The DA strain of Theiler's murine encephalomyelitis virus (DAV) causes a chronic demyelinating disease in susceptible mouse strains. To elucidate the pathogenesis of DAV-induced demyelination, the authors investigated the spatial and chronologic relationship between virus (antigen and RNA), myelin-specific mRNAs, and demyelination in DAV-infected mice using immunohistochemistry, in situ hybridization, and slot blot hybridization analyses. In spinal cord white matter, viral RNA was detected easily in ventral root entry zones 1 to 2 weeks after infection. Viral RNA increased to maximum levels by 4 weeks after infection, which was associated with inflammation and mild demyelination. At 8 to 12 weeks after infection, when demyelination became most extensive, viral RNA was significantly decreased. Demyelination did not chronologically or spatially parallel the presence of viral RNA within the spinal cord. Decrease of myelin-specific mRNAs, including myelin-basic protein and proteolipid protein mRNAs, was observed within the demyelinating lesions with or without detectable viral RNA. These results indicate that a viral infection of white matter in the early phase of the infection initiates spinal cord disease leading to demyelination, but later an ongoing immunopathologic process contributes to the presence of extensive demyelination.
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PMID:The relationship between viral RNA, myelin-specific mRNAs, and demyelination in central nervous system disease during Theiler's virus infection. 226 Jun 33

Amino acid sequence homology was found between viral and host encephalitogenic protein. Immune responses were then generated in rabbits by using the viral peptide that cross-reacts with the self protein. Mononuclear cell infiltration was observed in the central nervous systems of animals immunized with the viral peptide. Myelin basic protein (MBP) is a host protein whose encephalitogenic site of ten amino acids induces experimental allergic encephalomyelitis. By computer analysis, hepatitis B virus polymerase (HBVP) was found to share six consecutive amino acids with the encephalitogenic site of rabbit MBP. Rabbits given injections of a selected eight- or ten-amino acid peptide from HBVP made antibody that reacted with the predetermined sequences of HBVP and also with native MBP. Peripheral blood mononuclear cells from the immunized rabbits proliferated when incubated with either MBP or HBVP. Central nervous system tissue taken from these rabbits had a histologic picture reminiscent of experimental allergic encephalomyelitis. Thus, viral infection may trigger the production of antibodies and mononuclear cells that cross-react with self proteins by a mechanism termed molecular mimicry. Tissue injury from the resultant autoallergic event can take place in the absence of the infectious virus that initiated the immune response.
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PMID:Amino acid homology between the encephalitogenic site of myelin basic protein and virus: mechanism for autoimmunity. 241 48

Lewis and Brown Norway rats were infected at different ages with the neurotropic murine coronavirus strain, JHM and the resultant central nervous system diseases were studied. Suckling rats of both strains came down with a fatal, acute encephalomyelitis. Weanling Lewis rats developed a subacute demyelinating encephalomyelitis which neuropathologically revealed changes of an immunopathologic reaction. In contrast, Brown Norway rats developed a clinically silent subacute demyelinating encephalomyelitis with a persistent JHM virus infection which was less severe and quite different from the subacute demyelinating encephalomyelitis in Lewis rats with respect to size, distribution, and localization of the demyelinating plaques as well as the type of infiltrating cells. In addition, infected Lewis rats showed a pronounced lymphocyte proliferation to myelin basic protein and JHM virus whereas lymphocytes from infected Brown Norway rats did not react to these two antigens. These observations demonstrate the pathogenetic importance of host factors in the development of virus-induced demyelination.
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PMID:Comparative analysis of coronavirus JHM-induced demyelinating encephalomyelitis in Lewis and Brown Norway rats. 244 66

Intracerebral inoculation of weanling Lewis rats with measles virus led to the development of subacute measles encephalomyelitis (SAME) 4-8 weeks after infection. The disease is characterized pathologically by an intense inflammatory infiltration within both the white and grey matter of the central nervous system (CNS) without apparent demyelination. Both during and after SAME splenic lymphocytes from these animals could be restimulated in vitro to proliferate in the presence of myelin base protein (MBP). MBP-specific class II MHC-restricted T cell lines were isolated from this cell population. They were shown to exhibit no cross-reactivity with measles virus and to induce experimental allergic encephalitis (EAE) in naive syngeneic recipients following adoptive transfer. The clinical and histopathological signs of this T cell-mediated disease were identical to that seen in classical T cell-mediated EAE. A humoral immune response to MBP was only detected in a limited number of those rats with SAME. These results indicate that autoimmune reactions to brain antigen can arise during measles virus infection which may contribute to the pathogenesis of measles virus-associated encephalomyelitis.
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PMID:Induction of autoimmune reactions to myelin basic protein in measles virus encephalitis in Lewis rats. 244 22

Infections of rodents by murine coronaviruses can lead to chronic diseases of the central nervous system. These infections are interesting systems to study mechanisms which could be relevant for the pathogenesis of certain human diseases. One major factor influencing the outcome of infection is related to the virus. To understand the virological basis for neurovirulence we compared JHM-virus isolates with different biological properties. JHM-Wt causes only acute disease, JHM-Ts43 a demyelinating encephalomyelitis and a virus shedded from persistently infected cells (JHM-Pi) is not virulent at all. The spread of these viruses in glial cell cultures reflects their different neurovirulence for animals. The peplomer E2 of these viruses reveals structural and antigenic differences. We characterised the epitopes of E2 with a panel of monoclonal antibodies. Four epitopes are associated with regions important for neutralisation, cell fusion and attachment. More than five epitopes are not related to such functions. Epitopes differ in their location and accessibility on the E2 protein subunits between JHM-Wt, JHM-Ts43 and JHM-Pi. To identify epitopes in regions important for pathogenesis, we performed animal studies with variants selected by monoclonal antibodies. Variants changed in a defined epitope (E2-Ba) induce in Balb/c mice a chronic disease. Variants changed in only one of the other three neutralisation epitopes induce acute disease. These results support and extend the observation that the peplomer protein E2 is a major determinant for virulence and antigenic variability of coronaviruses 1,4,5,6,8,10,17,19,22,23. Increasing evidence had been obtained that certain structural features of this protein are important for the cell tropism of the virus. Furthermore, this protein influences strongly the type and specificity of immune responses against viral and host antigens. The highly advanced knowledge on structure and replication of coronaviruses will be of great value to analyze further mechanisms leading to inflammatory demyelinating diseases associated with a persistent virus infection.
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PMID:Coronavirus JHM induced demyelinating disease: specific domains on the E2-protein are associated with neurovirulence. 244 42

Thirteen dogs with encephalomyelitis attributable to canine distemper virus infection were classified into 3 groups on the basis of histopathologic evidence of virus-induced lesions in CNS tissue. Analysis of data indicated a similarity within groups when arranged by age, clinical neurologic signs, and alterations in the CSF electrophoretic protein values. Comparison with results in dogs with experimentally induced canine distemper encephalomyelitis suggested that when grouped by age, CSF electrophoretic values are helpful in predicting the CNS histopathologic changes in dogs with naturally acquired canine distemper encephalomyelitis.
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PMID:Electrophoretic determination of albumin and gamma globulin concentrations in the cerebrospinal fluid of dogs with encephalomyelitis attributable to canine distemper virus infection: 13 cases (1980-1987). 247 52

Chronic Theiler's murine encephalomyelitis virus infection of susceptible mice is an animal model for human demyelinating diseases. Previously we described an altered and diminished pattern of central nervous system disease in immunocompetent SJL/J mice infected with a variant virus. This variant virus H7A6-2 was selected with a neutralizing mAb recognizing the capsid protein VP-1 of Theiler's virus. Here we characterize the variant virus by ELISA and neutralization assays and by sequencing selected regions of the viral RNA genome and relate the alteration to disease. The variant virus contains one single point mutation within a neutralizing epitope of VP-1. This nucleotide change lead to an amino acid replacement at amino acid 101 of VP-1, a threonine (wild type) to an isoleucine (variant). Model building based on sequence alignments and the known structure of the related Mengo virus indicates that the altered amino acid is located in an exposed loop on the surface of the virus at the periphery of a site that has been proposed to be the receptor binding site. The results of ELISA, neutralization assay, and direct RNA sequencing provide for the first time an opportunity to precisely map an important structural determinant of neurovirulence.
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PMID:Alteration of amino acid 101 within capsid protein VP-1 changes the pathogenicity of Theiler's murine encephalomyelitis virus. 247 6

Viruses can initiate disease by many different means. Direct viral, immune mediated and host factors all play important parts. Molecular mimicry or having cross-reacting determinants that result in immune responses which have the potential to cause damage can be incorporated into this framework. Here, autoimmune responses generated by virus infection have been presented in relation to these other parameters. The cross-reacting immune response originally generated by virus would have to be directed toward or involve a disease inducing site such as an EAE (encephalitogenic), thyroiditis, or diabetogenic site. If the cross-reaction took place at a nondisease inducing site, the ensuring immune response may result in the production of autoantibodies, however no disease would occur. In other systems autoantibodies can potentiate an ongoing inflammatory response. This may be the case that is described here with Theiler's murine encephalomyelitis virus infection. Lastly, viruses having common determinants with MHC determinants may modify immune responses leading to immunosuppression and allowing virus to persist. In addition, similar determinants may lead to disease by an alternative route. For example, we have described a region of human cytomegalovirus that has a common determinant with HLA DR beta chain. This region is associated with diabetes in humans (Todd et al. 1988). Thus, many factors are involved in the outcome of disease induction by viruses of which autoimmunity is one.
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PMID:Is Theiler's murine encephalomyelitis virus infection of mice an autoimmune disease? 253 48

Theiler's murine encephalomyelitis virus infection of mice is an animal model for human demyelinating diseases. To further define the role of this virus in the disease process, we selected a virus variant resistant to neutralization by a monoclonal antibody to VP-1. This virus variant was then injected into SJL/J mice. Central nervous system tissue was compared between variant virus- and wild-type virus-infected mice. Within the brain, no large differences were observed between the two groups as to the distribution of inflammatory infiltrates around the injection site and the number of viral antigen-positive cells during the first weeks of the observation period. In contrast, in the spinal cord major differences were found between variant virus- and wild-type virus-infected mice regarding the number of inflammatory lesions, infected cells, and the size of the areas involved with time. By immunohistochemistry, equivalent numbers of infected cells could be found in the spinal cord 1 week postinfection (p.i.): however, after that time, the number of infected cells in the wild-type virus-infected mice continued to increase, whereas the virus-positive cells from the variant virus-infected mice gradually decreased. Thus, the number of viral antigen-containing cells peaked by 1 week p.i. in the variant virus-infected animals. Conversely, the number of infected cells in the spinal cords from mice inoculated with wild-type virus steadily increased until 8 weeks p.i. At this time (8 weeks p.i.), no more variant virus antigen-positive cells could be observed within the spinal cord. Plaque assay of central nervous system tissue confirmed these differences between the two groups observed by immunohistochemistry. No infectious variant virus could be isolated after 2 weeks p.i. from the brain and 4 weeks p.i. from the spinal cord, whereas infectious wild-type virus could be detected up to the end of the observation period (12 weeks p.i.). Virus which was isolated from variant virus-infected mice still retained the neutralization-resistant phenotype. These studies emphasize the important biological in vivo activity of Theiler's virus VP-1 in determining neurovirulence.
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PMID:A neutralization-resistant Theiler's virus variant produces an altered disease pattern in the mouse central nervous system. 253 41


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