Interferon induction by 11 temperature-sensitive (ts) mutants of the HR strain, and 38 ts mutants of the AR339 strain of Sindbis virus was investigated. All HR and AR339 mutants induced interferon at 30 °C. Induction by the mutants at the restrictive temperature (39 °C) was dependent on the time of incubation, and, in some instances, on the input multiplicity. At an input multiplicity of 5, and after an incubation time of 16 h at 39 °C, induction by the AR339 mutants was dependent on virus RNA synthesis. All HR mutants showing detectable RNA synthesis at 39 °C induced interferon, but of those showing undetectable RNA synthesis at 39 °C, three induced interferon and three did not. At 42 °C, RNA synthesis by the HR wild-type and all ts mutants was depressed, and only one mutant and the wild type induced interferon. Temperature shift experiments showed that interferon induction was dependent on an early virus function. It is postulated that interferon induction is dependent on a low threshold level of RNA synthesis occurring early in infection.


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