Institute of Biosciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor DE, Malaysia.
Virol J. 2012 Aug 30;9:179. doi: 10.1186/1743-422X-9-179.
Recently it was shown that following infection of HeLa cells with Newcastle disease virus (NDV), the matrix (M) protein binds to Bax and subsequently the intrinsic pathway of apoptosis is activated. Moreover, there was very little alteration on mRNA and protein levels of Bax and Bcl-2 after infection with NDV.
In order to further investigate the role of members of the Bcl-2 family, Bax-knockout and wild-type HCT116 cells were infected with NDV strain AF2240. Although both cells underwent apoptosis through the activation of the intrinsic pathway and the release of cytochrome c from mitochondria, the percentage of dead Bax-knockout cells was significantly lower than wt cells (more than 10% at 48 h post-infection). In a parallel experiment, the effect of NDV on HT29 cells, that are originally Bcl-2-free, was studied. Apoptosis in HT29 cells was associated with Bax redistribution from cytoplasm to mitochondria, similar to that of HeLa and wt HCT116 cells.
Although the presence of Bax during NDV-induced apoptosis contributes to a faster cell death, it was concluded that other apoptotic protein(s) upstream of mitochondria are also involved since cancer cells die whether in the presence or absence of Bax. Therefore, the classic Bax/Bcl-2 ratio may not be a major determinant in NDV-induced apoptosis.
最近的研究表明，新城疫病毒（NDV）感染 HeLa 细胞后，基质（M）蛋白与 Bax 结合，随后内在凋亡途径被激活。此外，NDV 感染后 Bax 和 Bcl-2 的 mRNA 和蛋白水平几乎没有改变。
为了进一步研究 Bcl-2 家族成员的作用，用 NDV 株 AF2240 感染 Bax 敲除和野生型 HCT116 细胞。尽管两种细胞都通过内在途径的激活和线粒体释放细胞色素 c 来诱导凋亡，但 Bax 敲除细胞的死亡率明显低于 wt 细胞（感染后 48 小时超过 10%）。在平行实验中，研究了 NDV 对原本没有 Bcl-2 的 HT29 细胞的影响。HT29 细胞的凋亡与 Bax 从细胞质向线粒体的重新分布有关，与 HeLa 和 wt HCT116 细胞相似。
虽然 Bax 在 NDV 诱导的凋亡过程中的存在有助于更快的细胞死亡，但我们推断，线粒体上游的其他凋亡蛋白（s）也参与其中，因为癌细胞无论是否存在 Bax 都会死亡。因此，经典的 Bax/Bcl-2 比值可能不是 NDV 诱导凋亡的主要决定因素。
