Establishment of Persistent Infection in Mouse Cells by Sindbis Virus and its Temperature-sensitive Mutants

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Abstract
Summary 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 °C. At 30 °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 °C (the restrictive temperature) but the virus was eventually eliminated. At 30 °C (the permissive temperature) in L cells all mutants established persistent infection. In ME cells at 30 °C, RNA- mutants (unable to synthesize virus-specified RNA at 39 °C) established persistent infection whereas the cells did not recover from infection with RNA+ mutants (able to synthesize virus-specified RNA at 39 °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 °C and 39 °C, but its activity could not be detected in either cell line at 30 °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 °C is probably due to the action of interferon.

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