The uncoupled relationship between the temperature sensitivity and neurovirulence in mice of mutants of vesicular stomatitis virus

Inoculation of wild-type (wt) VSV intracerebrally (i.c.) in Swiss weanling mice results in a rapidly fatal illness with death in 2 to 3 days. In contrast, i.c. inoculation of temperature-sensitive (ts) VSV mutants G31 and G22, but not ts G11 or ts G41, results in a more slowly progressive CNS disease with distinct neurologic signs. Studies undertaken to evaluate the neurovirulence of ts VSV mutants indicated that the ability of ts mutants to produce pathologic changes in the CNS of mice appeared related to their ability to replicate to high titer in brain and spinal cord. However, replication of ts VSV mutants in brain alone was not sufficient to produce clinical illness. More importantly, the ability of ts VSV mutants to replicate at non-permissive temperatures in vitro did not appear to correlate with neurovirulence. VSV harvests from brains and spinal cords of mice infected with each of the ts mutants were temperature insensitive. In spite of their temperature-insensitivity, the biologic behavior of viruses recovered from CNS tissues was, surprisingly, not that which was characteristic of revertant clones. Virus isolates recovered from infected CNS tissues, despite their temperature-insensitivity, behaved biologically like the original stocks of ts mutant virus. These data suggest that temperature-sensitivity is not directly correlated with the unique pathogenesis elicited by infection with ts VSV mutants.