Pathogenesis of Temperature-Sensitive Mutants of Sindbis Virus in the Embryonated Egg. III. Autologous, Homologous, and Heterologous Interference

Two temperature-sensitive (ts) mutants of Sindbis virus able to synthesize RNA, but not two ts mutants defective in viral RNA synthesis, reduced the lethality of the superinfecting heat-resistant parent strain of Sindbis virus in embryonated chicken eggs as compared with results in controls. Autologous interference (of mutant with parent) was observed under a variety of conditions. Time-course studies in one selected system showed that lower titers of superinfecting parent virus were detected in doubly infected eggs than in controls eggs infected with only parent virus. Homologous interference with lethality (of mutant with an immunologically different yet related group A togavirus) was observed when the interfering virus was a ts mutant of either Sindbis virus or Eastern equine encephalitis virus. Heterologous interference (mutant with unrelated virus) could also be demonstrated with a ts mutant of Sindbis virus against vaccinia virus-induced pock formation or death. In an autologous interference experiment, in which the ts mutant of Sindbis virus was administered by the yolk sac route and the egg was challenged with parent heat-resistant Sindbis virus by the allantoic route, an interferon-like substance was found in the allantoic fluids at the time of challenge. It is concluded that certain ts viruses of togavirus group A can induce autologous, homologous, and heterologous viral interference in vivo.