SELECTED MUTANTS OF MOUSE HEPATITIS-VIRUS TYPE-4 (JHM-STRAIN) INDUCE DIFFERENT CNS DISEASES - PATHOBIOLOGY OF DISEASE INDUCED BY WILD-TYPE AND MUTANT-TS8 AND MUTANT-TS15 IN BALB/C AND SJL/J MICE

  • 1 January 1982
    • journal article
    • research article
    • Vol. 109  (2) , 157-168
Abstract
The model system of CNS disease induced by mouse hepatitis virus type 4 (MHV-4) is explored by comparison of wild type (wt) MHV-4 and 2 temperature-sensitive (ts) mutants, designated ts8 and ts15, in BALB/c and SJL/J mice. In BALB/c mice, 3 plaque-forming units (PFU) of wt MHV-4 given intracerebrally caused fatal encephalomyelitis in all mice by 7 days after infection, with spread of virus outside the CNS, especially to liver. In SJL/J mice, 3 PFU of wt virus was cleared within 2-3 days, with little spread, and up to 100 PFU failed to cause fatal encephalomyelitis. Larger amounts of virus, like 1000 PFU, caused fatal encephalomyelitis in SJL/J mice. In contrast, 104 PFU of MHV-4 ts8 did not cause death in either BALB/c or SJL/J mice, and persisted in the CNS of both strains while retaining its ts phenotype. There was significantly less spread of virus outside the CNS. BALB/c mice usually showed demyelination, remyelination, and recurrent demyelination with ts8, while SJL/J mice only rarely had lesions. Intracerebral inoculation with 104 PFU of MHV-4 ts15 was associated with a persistent infection in CNS and liver of BALB/c mice; only occasional demyelination and hepatic lesions occurred. ts15 did not cause death in either BALB/c or SJL/J mice and did not cause histopathologic injury in SJL/J mice.