Naturally occurring substitutions in the P/V gene convert the noncytopathic paramyxovirus XXXX into a virus that induces alpha/beta interferon synthesis and cell death.

@entity1 @entity22218 @entity2391 @entity6897 @entity3027
The V protein of the paramyxovirus @entity22218 ) is responsible for targeted degradation of @entity6897 and the block in alpha/beta interferon ( @entity3027 /beta) signaling that occurs after SV5 infection of @entity1 cells. We have analyzed the growth properties of a recombinant SV5 that was engineered to be defective in targeting @entity6897 degradation. A recombinant SV5 (rSV5-P/V-CPI-) was engineered to contain six naturally occurring P/V protein mutations, three of which have been shown in previous transfection experiments to disrupt the V-mediated block in @entity3027 /beta signaling. In contrast to wild-type (WT) SV5, @entity1 cells infected with rSV5-P/V-CPI- had @entity6897 levels similar to those in mock-infected cells. Cells infected with rSV5-P/V-CPI- were found to express higher-than-WT levels of viral proteins and mRNA, suggesting that the P/V mutations had disrupted the regulation of viral RNA synthesis. Despite the inability to target @entity6897 for degradation, single-step growth assays showed that the rSV5-P/V-CPI- mutant virus grew better than WT SV5 in all cell lines tested. Unexpectedly, cells infected with rSV5-P/V-CPI- but not WT SV5 showed an activation of a reporter gene that was under control of the @entity2391 promoter. The secretion of IFN from cells infected with rSV5-P/V-CPI- but not WT SV5 was confirmed by a bioassay for IFN. The rSV5-P/V-CPI- mutant grew to higher titers than did WT rSV5 at early times in multistep growth assays. However, rSV5-P/V-CPI- growth quickly reached a final plateau while WT rSV5 continued to grow and produced a final titer higher than that of rSV5-P/V-CPI- by late times postinfection. In contrast to WT rSV5, infection of a variety of cell lines with rSV5-P/V-CPI- induced cell death pathways with characteristics of apoptosis. Our results confirm a role for the SV5 V protein in blocking IFN signaling but also suggest new roles for the P/V gene products in controlling viral gene expression, the induction of @entity3027 /beta synthesis, and virus-induced apoptosis.
