Relationship between neurovirulence and temperature sensitivity of an attenuated western equine encephalitis virus

Summary An attenuated strain of western equine encephalitis virus which arose spontaneously during a persistent infection was compared with the virulent parent strain for its growth potential over the temperature range 32° to 42° C. At 42° C, the attenuated strain proved unable to grow in a one-step growth experiment and failed to produce plaques. The temperature sensitivity was found to be due not to inactivation at 42° C of the attenuated virus particles, but to some temperature sensitive step occurring late in the replicative cycle. When the attenuated strain was passaged at 41 °C and clones selected for growth at this temperature, the resulting population did not regain the neurovirulence of the wild-type virus. In contrast, when virulent-revertants were selected from the attenuated, temperature-sensitive virus, temperature sensitivity remained unchanged. These findings indicated a lack of covariation of the temperature sensitivity and neurovirulence of western equine encephalitis virus, and suggest that mutation to avirulence and temperature sensitivity probably occurred independently.