Dillon Patrick J, Wansley Elizabeth K, Young Virginia A, Alexander-Miller Martha A, Parks Griffith D
Department of Microbiology and Immunology, Wake Forest University, School of Medicine, Winston-Salem, NC 27157-1064, USA.
J Gen Virol. 2006 Dec;87(Pt 12):3643-3648. doi: 10.1099/vir.0.82242-0.
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.
副粘病毒猴病毒5（SV5）在人上皮细胞和成纤维细胞中大多无细胞病变效应。WF-PIV先前已被描述为一种天然存在的SV5变体，其编码的P蛋白和V蛋白分别在8个和5个氨基酸位置上与野生型（WT）SV5蛋白不同。在本研究中，结果表明WF-PIV与WT SV5相似，在A549肺上皮细胞中大多无细胞病变效应。然而，将WF-PIV的P/V基因替换到WT SV5的背景中产生了一种杂交病毒（P/V-WF），该病毒诱导了亲代病毒均未出现的凋亡性细胞死亡。P/V-WF嵌合体导致HeLa细胞死亡和诱导凋亡的动力学与先前描述的P/V-CPI-嵌合体不同，其速度较慢且程度较轻。caspase-9抑制剂可有效减少P/V-WF嵌合体对HeLa细胞的杀伤，但caspase-8抑制剂则无效。这些结果表明，两种无细胞病变效应的SV5变体的P/V基因交换可产生诱导凋亡的嵌合体，并且SV5 P/V基因产物在限制凋亡中的作用可能取决于其在天然病毒基因组背景下的表达。
