Establishment of persistent infection in mouse cells by Sindbis virus and its temperature-sensitive mutants.

The ability of wild-type (wt) Sindbis virus and six temperature-sensitive (ts) mutants to establish persistent infection in mouse L cells and a line of mouse embryo (ME) cells was determined. The wt established persistent infection in both ME cells and L cells at 39 degrees C. At 30 degrees C the wt established persistent infection in L cells but not ME cells, which did not recover from the initial infection. For the ts mutants, both cell lines survived the initial infection at 39 degrees C (the restrictive temperature) but the virus was eventually eliminated. At 30 degrees C (the permissive temperature) in L cells all mutants established persistent infection. In ME cells at 30 degrees C, RNA- mutants (unable to synthesize virus-specified RNA at 39 degrees C) established persistent infection whereas the cells did not recover from infection with RNA+ mutants (able to synthesize virus-specified RNA at 39 degrees C). The wt virus was less cytopathic in L cells than in BHK or ME cells. Interferon was produced by both L and ME cells at 30 degrees C and 39 degrees C, but its activity could not be detected in either cell line at 30 degrees C. It is proposed that establishment of persistent infection is dependent on reduced cytopathogenicity in the early stage of infection, and that further evolution of the virus then occurs to a less cytopathic form. Elimination of the virus at 39 degrees C is probably due to the action of interferon.