Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del IPN, Av. IPN 2508. Col. San Pedro Zacatenco, México, D.F CP 07360, Mexico.
Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del IPN, México City, Mexico.
Virology. 2019 Jan 15;527:146-158. doi: 10.1016/j.virol.2018.11.017. Epub 2018 Dec 4.
Calicivirus infection causes intrinsic apoptosis, leading to viral propagation in the host. During murine norovirus infection, a reduction in the anti-apoptotic protein survivin has been documented. Here we report that in feline calicivirus infection, a downregulation of the anti-apoptotic proteins survivin and XIAP occur, which correlates with the translocation of the pro-apoptotic protein Smac/DIABLO from the mitochondria to the cytoplasm and the activation of caspase-3. Inhibition of survivin degradation by lactacystin treatment caused a delay in apoptosis progression, reducing virus release, without affecting virus production. However, the overexpression of survivin caused a negative effect in viral progeny production. Overexpression of the leader of the capsid protein (LC), but not of the protease-polymerase NS6/7, results in the downregulation of survivin and XIAP, caspase activation and mitochondrial damage. These results indicate that LC is responsible for the induction of apoptosis in transfected cells and most probably in FCV infection.
杯状病毒感染会导致细胞发生内在凋亡，从而促进病毒在宿主体内的增殖。在感染鼠诺如病毒时，已发现抗凋亡蛋白生存素的表达减少。在此我们报告，在猫杯状病毒感染中，抗凋亡蛋白生存素和 XIAP 下调，这与促凋亡蛋白 Smac/DIABLO 从线粒体易位到细胞质以及 caspase-3 的激活相关。用乳胞素抑制生存素的降解会导致细胞凋亡进程延迟，从而减少病毒释放，但不影响病毒的产生。然而，生存素的过表达会对病毒子代的产生产生负面影响。衣壳蛋白（LC）的前导区的过表达（但不是蛋白酶-聚合酶 NS6/7）会导致生存素和 XIAP 的下调、半胱天冬酶的激活和线粒体损伤。这些结果表明，LC 负责诱导转染细胞凋亡，很可能也负责 FCV 感染中的细胞凋亡。
