Murine central nervous system infection by a viral temperature-sensitive mutant: a subacute disease leading to demyelination.
Temperature-sensitive (ts) mutants of viruses may represent an important mechanism for viral persistence. Ts mutants of different complementation groups of vesicular stomatitus virus (VSV) have shown various disease patterns in infected mice which were at variance with the clinical and pathologic features of wild-type virus infection. To investigate whether neurovirulence of different ts mutants was dependent on the individual mutant or on the biochemical defect(s) common to all members of a complementation group, we infected mice with ts G32 VSV, a mutant of the same complementation group III as the previously described ts G31 VSV. Pathologic changes in infected mice were sharply different from those produced by ts G31 VSV and actually similar to those produced by ts G41 VSV, a member of Complementation Group IV, also previously described. These results suggest that the biologic behavior of ts mutants is dependent on the individual characteristics of each mutant. The most important alterations by ts G32 VSV were in the white matter of brain and spinal cord, where extensive inflammatory demyelination was observed. Lack of inflammation and demyelination in similarly infected nude mice would suggest that, in this infection, demyelination is produced by the host immune response rather than by direct viral myelinolytic activity. Such findings are similar to those we described in other viral infections and support the hypothesis of a common host-mediated pathway leading to demyelination in a variety of unrelated viral infections. These conclusions may have relevance to human demyelinating diseases.
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D001369:Axons / Q000473:pathology / Q000648:ultrastructure; D003337:Corpus Callosum / Q000473:pathology / Q000648:ultrastructure; D003711:Demyelinating Diseases / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009154:Mutation; D013116:Spinal Cord / Q000473:pathology / Q000648:ultrastructure; D013696:Temperature; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics; D014777:Virus Diseases / Q000276:immunology / Q000473:pathology*
D000956:Antigens, Viral