Comparison of central nervous system (CNS) disease produced by wild type (WT) and temperature sensitive (TS) mutants of vesicular stomatitis virus (VSV)

Intracerebral (i.c.) injection of wt VSV in Swiss weanling mice produced a rapidly fatal encephalitis with death of mice in 2-3 days. Histopathologically, such mice exhibited minimal changes of encephalitis on light microscopy. In contrast to the highly virulent, rapidly fatal CNS infection seen after i.c. inoculation of wt VSV, infection with ts (-10°C) and ts 31, but not ts 11 or ts 41, produced a more slowly progressive CNS infection characterized by hind limb paralysis and death 6-9 days after infection. Histopathologically CNS infection with ts 22 and ts 31 was associated with extensive spongiform changes in the grey matter of the spinal cord. Ultrastructurally, these vacuolar changes appeared to be principally of dendritic or astrocytic origin. Inoculation i.c. of ts 11 or ts 41, on the other hand, results neither in clinical illness nor histopathological lesions. An analysis of viral titers in brain and spinal cord after CNS infection with the ts mutants demonstrated a lack of correlation between appearance of spongiform myelopathy and either the growth or persistence of various ts mutants in the CNS. These results suggest that certain ts mutants of VSV possess the capability of altering CNS disease usually associated with VSV and of producing histopathological lesions bearing some similarity to the slow viral diseases of animals and man.