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The Induction of Interferon by Temperature-Sensitive Mutants of Sindbis Virus: Its Relationship to Double-Stranded RNA Synthesis and Cytopathic Effect
Abstract
SUMMARY
Sindbis virus strain AR339 induces interferon by 3 h after infection at 39 °C and by 8 h after infection at 30 °C. The time course of interferon induction between 4 and 9 h after infection at the restrictive temperature (39 °C) was measured for 24 temperature-sensitive (ts) mutants, all of which induced interferon by 16 h after infection. Mutants showing total RNA synthesis at 39 °C greater than 10% of the wild-type level induced interferon with kinetics similar to the wild-type. Of those mutants showing 1 to 10% of the wild-type level of RNA synthesis at 39 °C, four induced interferon with kinetics similar to the wild type, whereas six showed a lag in induction. Nine mutants, showing 0 to 5% of the wild-type level of RNA synthesis at 39 °C, and the wild type, were examined for single and double-stranded RNA synthesis at 30 and 39 °C, using a combination of lithium chloride precipitation and CF11 cellulose chromatography. Six of these mutants showed a lag in interferon induction at 30 °C, while three showed no lag. For all nine mutants, double-stranded RNA synthesis at 39 °C was undetectable, although easily detectable for the wild type. Both the wild type and the mutants synthesized double-stranded RNA at 30 °C. For all mutants, time of interferon induction at 39 °C was correlated with c.p.e. as measured by trypan blue uptake 30 h after infection.
The mutant F104, showing undetectable RNA synthesis and a long lag in interferon induction at 39 °C, was examined for interferon to be induced with wild-type kinetics, and this was correlated with an increased c.p.e. 30 h after infection. Increased RNA synthesis and infectious virus production were detectable at 30 °C after an initial hour at 30 °C.
It is concluded that, for interferon to be induced with normal kinetics, early virus functions are required, but that normal levels of double-stranded RNA synthesis are not necessary. The events which lead to interferon induction also lead to visible c.p.e.
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© Journal of General Virology 1976