Apoptosis induction and interferon signaling but not IFN-beta promoter induction by an SV5 P/V mutant are rescued by coinfection with wild-type SV5.
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-beta 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 (DeltaPsi(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-beta promoter by rSV5-P/V-CPI- infection. However, the IFN-beta 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.
Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1064, USA.
Elizabeth K
EK
Wansley
Jason M
JM
Grayson
Griffith D
GD
Parks
D017209:Apoptosis; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials; D008928:Mitochondria; D009154:Mutation; D045402:Parainfluenza Virus 5 / Q000235:genetics / Q000472:pathogenicity*; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016601:RNA-Binding Proteins; D015398:Signal Transduction; D015533:Transcriptional Activation; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D015678:Viral Structural Proteins / Q000235:genetics* / Q000378:metabolism
D016898:Interferon-alpha; C097018:P protein, Simian parainfluenza virus 5; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; C097019:V protein, Simian parainfluenza virus 5; D014764:Viral Proteins; D015678:Viral Structural Proteins; D016899:Interferon-beta