Targeted recombination between MHV-2 and MHV-A59 to study neurotropic determinants of MHV.
MHV-A59 produces acute encephalitis, acute hepatitis and chronic demyelination in infected mice. MHV-2 produces only hepatitis and mild meningitis but without encephalitis or demyelination. We have previously studied a set of recombinant viruses between these two strains. The common denominator of viruses that produced encephalitis was a membrane (M) gene derived from MHV-A59. Thus to study the potential contribution of the M gene to acute encephalitis, chimeric viruses were produced in which the M gene of MHV-A59 was substituted with the M gene of MHV-2 by targeted recombination. A control virus was produced in which the M gene of A59 was recombined back into an A59 background. Viruses were then analyzed for their biologic properties and compared with the phenotypes of MHV-A59 and MHV-2 by histopathology and plaque assays for viral titers in organs following intracerebral (IC) inoculation. All three chimeric viruses had a phenotype similar to MHV-A59. Thus, the replacement of the M gene of MHV-A59 with that of MHV-2 is insufficient to produce a phenotype that lacks encephalitis similar to MHV-2.
Department of Pathology and Laboratory Medicine, University of Pennsylvania, School of Medicine, Philadelphia 19104, USA.
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E
Lavi
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Kuo
J A
JA
Haluskey
P S
PS
Masters
D000818:Animals; D003711:Demyelinating Diseases / Q000821:virology; D007739:L Cells; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D006517:Murine hepatitis virus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D011995:Recombination, Genetic; D014774:Virulence; D014779:Virus Replication