Pathogenicity of an attenuated, temperature-sensitive mutant of western equine encephalitis virus induced by a chemical mutagen.

To know the pathogenicity of the chemically induced, temperature-sensitive (ts) mutant of western equine encephalitis virus, designated tsNG39, the lethality for mice injected with tsNG39, virus yield, interferon production, and histological changes in the brains of these mice were examined in parallel with those of mice inoculated with the parent strain (PS). All of the mice injected intracranially with PS died within 3.5 days after injection irrespective of the inoculum size of virus, whereas the lethality of the mice inoculated with tsNG39 varied from 94.3 to 65.5% among groups of mice and this variation seemed to be correlated with the inoculum size of virus rather than with the maximum virus titer in the brain. By histological examination, two types of changes in the brain were distinguished, inflammatory and degenerative ones. Inflammatory changes were more prominent in the brains injected with tsNG39 than in those receiving PS. Degenerative changes were dominant in the brains injected with PS, but they were slight in the earlier phase of infection by tsNG39 became prominent only later. The degree of degenerative change was well correlated with both the virus titer in the mouse brain and the death pattern of mice injected with PS or tsNG39. Since degenerative changes are thought to be caused by the direct effect of injected virus, these results indicated that the factor responsible for the low virulence of tsNG39 was the slow viral growth in the brain.