Department of Pathology and Animal Health, Infectious Diseases, Faculty of Veterinary Medicine, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy.
Vet Microbiol. 2010 Feb 24;141(1-2):36-45. doi: 10.1016/j.vetmic.2009.09.001. Epub 2009 Sep 11.
A previous study demonstrated that infection of a canine fibrosarcoma cell line (A-72 cells) by canine coronavirus (CCoV) resulted in apoptosis (Ruggieri et al., 2007). In this study, we investigated the cell death processes during infection and the underlying mechanisms. We found that CCoV-II triggers apoptosis in A-72 cells by activating initiator (caspase-8 and -9) and executioner (caspase-3 and -6) caspases. The proteolytic cleavage of poly(ADP-ribose) polymerases (PARPs) confirmed the activation of executioner caspases. Furthermore, CCoV-II infection resulted in truncated bid (tbid) translocation from the cytosolic to the mitochondrial fraction, the cytochrome c release from mitochondria, and alterations in the pro- and anti-apoptotic proteins of bcl-2 family. Our data indicated that, in this experimental model, both intrinsic and extrinsic pathways are involved. In addition, we demonstrated that the inhibition of apoptosis by caspase inhibitors did not affect CCoV replication, suggesting that apoptosis does not play a role in facilitating viral release.
先前的一项研究表明，犬冠状病毒（CCoV）感染犬纤维肉瘤细胞系（A-72 细胞）会导致细胞凋亡（Ruggieri 等人，2007）。在这项研究中，我们研究了感染过程中的细胞死亡过程和潜在的机制。我们发现 CCoV-II 通过激活起始（半胱天冬酶-8 和 -9）和执行（半胱天冬酶-3 和 -6）半胱天冬酶来触发 A-72 细胞凋亡。多聚（ADP-核糖）聚合酶（PARPs）的蛋白水解裂解证实了执行半胱天冬酶的激活。此外，CCoV-II 感染导致截断的 bid（tbid）从细胞质向线粒体部分易位，细胞色素 c 从线粒体释放，以及 bcl-2 家族的促凋亡和抗凋亡蛋白的改变。我们的数据表明，在这个实验模型中，涉及内在和外在途径。此外，我们证明凋亡抑制剂对 CCoV 复制的抑制作用不影响凋亡，这表明凋亡在促进病毒释放中不起作用。
