Fischer Richard, Baumert Thomas, Blum Hubert-E
Department of Internal Medicine II, University of Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany.
World J Gastroenterol. 2007 Sep 28;13(36):4865-72. doi: 10.3748/wjg.v13.i36.4865.
Apoptosis is central for the control and elimination of viral infections. In chronic hepatitis C virus (HCV) infection, enhanced hepatocyte apoptosis and upregulation of the death inducing ligands CD95/Fas, TRAIL and TNFalpha occur. Nevertheless, HCV infection persists in the majority of patients. The impact of apoptosis in chronic HCV infection is not well understood. It may be harmful by triggering liver fibrosis, or essential in interferon (IFN) induced HCV elimination. For virtually all HCV proteins, pro- and anti-apoptotic effects have been described, especially for the core and NS5A protein. To date, it is not known which HCV protein affects apoptosis in vivo and whether the infectious virions act pro- or anti-apoptotic. With the availability of an infectious tissue culture system, we now can address pathophysiologically relevant issues. This review focuses on the effect of HCV infection and different HCV proteins on apoptosis and of the corresponding signaling cascades.
细胞凋亡对于控制和消除病毒感染至关重要。在慢性丙型肝炎病毒（HCV）感染中，肝细胞凋亡增强，死亡诱导配体CD95/Fas、肿瘤坏死因子相关凋亡诱导配体（TRAIL）和肿瘤坏死因子α（TNFα）上调。然而，大多数患者的HCV感染持续存在。细胞凋亡在慢性HCV感染中的影响尚未完全明确。它可能通过引发肝纤维化而有害，或者在干扰素（IFN）诱导的HCV清除中起关键作用。几乎所有的HCV蛋白都具有促凋亡和抗凋亡作用，尤其是核心蛋白和NS5A蛋白。迄今为止，尚不清楚哪种HCV蛋白在体内影响细胞凋亡，以及感染性病毒粒子是具有促凋亡还是抗凋亡作用。随着感染性组织培养系统的出现，我们现在能够解决病理生理学相关问题。本综述重点关注HCV感染和不同HCV蛋白对细胞凋亡的影响以及相应的信号级联反应。
