HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Atkins, G. J. Articles by Lancashire, C. L. Search for Related Content PubMed PubMed Citation Articles by Atkins, G. J. Articles by Lancashire, C. L. Agricola Articles by Atkins, G. J. Articles by Lancashire, C. L.

The Induction of Interferon by Temperature-Sensitive Mutants of Sindbis Virus: Its Relationship to Double-Stranded RNA Synthesis and Cytopathic Effect

Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, England

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.

Received 6 August 1975; accepted 1 October 1975.