Exchange of P/V genes between two non-cytopathic simian virus 5 variants results in a recombinant virus that kills cells through death pathways that are sensitive to caspase inhibitors.
The paramyxovirus Simian virus 5 (SV5) is largely non-cytopathic in human epithelial and fibroblast cells. WF-PIV has been described previously as a naturally occurring SV5 variant that encodes P and V proteins differing from the wild-type (WT) SV5 proteins in eight and five amino acid positions, respectively. In this study, it is shown that WF-PIV is like WT SV5 by being largely non-cytopathic in A549 lung epithelial cells. However, substitution of the WF-PIV P/V gene into the background of WT SV5 resulted in a hybrid virus (P/V-WF) that induced apoptotic cell death not seen with either of the parental viruses. The kinetics of HeLa cell killing and induction of apoptosis by the P/V-WF chimera differed from those of the previously described P/V-CPI- chimera by being slower and less extensive. HeLa cell killing by the P/V-WF chimera was effectively reduced by inhibitors of caspase-9, but not of caspase-8. These results demonstrate that an exchange of P/V genes from two non-cytopathic SV5 variants can produce apoptosis-inducing chimeras, and that the role of the SV5 P/V gene products in limiting apoptosis can be dependent on expression in the context of a native viral genome.
Dillon
Patrick J
PJ
Department of Microbiology and Immunology, Wake Forest University, School of Medicine, Winston-Salem, NC 27157-1064, USA.
Wansley
Elizabeth K
EK
Department of Microbiology and Immunology, Wake Forest University, School of Medicine, Winston-Salem, NC 27157-1064, USA.
Young
Virginia A
VA
Department of Microbiology and Immunology, Wake Forest University, School of Medicine, Winston-Salem, NC 27157-1064, USA.
Alexander-Miller
Martha A
MA
Department of Microbiology and Immunology, Wake Forest University, School of Medicine, Winston-Salem, NC 27157-1064, USA.
Parks
Griffith D
GD
Department of Microbiology and Immunology, Wake Forest University, School of Medicine, Winston-Salem, NC 27157-1064, USA.
D017209:Apoptosis; D061945:Caspase Inhibitors; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival; D003588:Cytopathogenic Effect, Viral / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000821:virology*; D006367:HeLa Cells; D006801:Humans; D045402:Parainfluenza Virus 5 / Q000235:genetics / Q000472:pathogenicity*; D010750:Phosphoproteins / Q000235:genetics*; D016601:RNA-Binding Proteins; D011995:Recombination, Genetic; D014764:Viral Proteins / Q000235:genetics*; D015678:Viral Structural Proteins / Q000235:genetics*
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; 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