Apoptosis induction and interferon signaling but not IFN-β promoter induction by an SV5 P/V mutant are rescued by coinfection with wild-type SV5

Abstract

Infection of human cells with the paramyxovirus simian virus 5 (SV5) results in minimal cytopathic effect, and host interferon (IFN) and apoptotic pathways are not activated. We have previously shown that an rSV5 containing six naturally occurring P/V gene substitutions (rSV5-P/V-CPI−) displays premature and elevated expression of viral RNA and protein. In addition, cells infected with rSV5-P/V-CPI− show induction of the IFN-β promoter as well as activation of IFN signaling and apoptotic pathways. In this article, we have tested the hypothesis that rSV5-WT can supply trans-acting factors that prevent host cell antiviral responses induced by rSV5-P/V-CPI−. During coinfection of human A549 cells, rSV5-WT blocked cell rounding, loss of cell volume, and DNA fragmentation induced by rSV5-P/V-CPI−, three later events in the apoptotic pathway, but was not able to block the loss of mitochondrial membrane potential (ΔΨ m ), an early event in the cell death process. As expected, IFN signaling was blocked during coinfections, and this was attributed to the loss of STAT1 induced by the rSV5-WT V protein. Surprisingly, simultaneous infection with rSV5-WT could not suppress the activation of the IFN-β promoter by rSV5-P/V-CPI− infection. However, the IFN-β promoter was not activated in cells that were first preinfected for 1 h with rSV5-WT and then subsequently infected with rSV5-P/V-CPI−. A model is proposed for activation of host responses to infection with the rSV5-P/V-CPI− mutant and the steps that are blocked by rSV5-WT.