Paramyxoviruses are reported to block apoptosis for their replication, but the mechanisms remain unclear. Furthermore, regulation of mitochondrial apoptosis by paramyxoviruses has been hardly reported. We investigated whether and how human parainfluenza virus type 2 (hPIV-2) counteracts apoptosis. Infection of recombinant hPIV-2 carrying mutated V protein showed higher caspase 3/7 activity and higher cytochrome release from mitochondria than wild type hPIV-2 infection. This indicates that V protein controls mitochondrial apoptosis pathway. hPIV-2 V protein interacted with Bad, an apoptotic promoting protein, and this interaction inhibited the binding of Bad to Bcl-X. V protein also bound to 14-3-3ε, which was essential for inhibition of 14-3-3ε cleavage. Our data collectively suggest that hPIV-2 V protein has two means of preventing mitochondrial apoptosis pathway: the inhibition of Bad-Bcl-X interaction and the suppression of 14-3-3ε cleavage. This is the first report of the mechanisms behind how paramyxoviruses modulate mitochondrial apoptosis pathways.

中文翻译：

---

人副流感病毒2型V蛋白通过两种途径抑制线粒体凋亡途径

据报道，副粘病毒可以阻止细胞凋亡的复制，但其机制仍不清楚。此外，副粘病毒对线粒体凋亡的调节几乎没有报道。我们研究了人类副流感病毒 2 型 (hPIV-2) 是否以及如何抵抗细胞凋亡。与野生型 hPIV-2 感染相比，携带突变 V 蛋白的重组 hPIV-2 的感染显示出更高的 caspase 3/7 活性和更高的线粒体细胞色素释放。这表明V蛋白控制线粒体凋亡途径。 hPIV-2 V蛋白与凋亡促进蛋白Bad相互作用，并且这种相互作用抑制Bad与Bcl-X的结合。 V 蛋白还与 14-3-3ε 结合，这对于抑制 14-3-3ε 裂解至关重要。我们的数据共同表明，hPIV-2 V 蛋白有两种预防线粒体凋亡途径的方法：抑制 Bad-Bcl-X 相互作用和抑制 14-3-3ε 裂解。这是副粘病毒调节线粒体凋亡途径背后机制的第一份报告。