Hepatitis C Virus Infection of Cultured Human Hepatoma Cells Causes Apoptosis and Pyroptosis in Both Infected and Bystander Cells.
Hepatitis C Virus Infection of Cultured Human Hepatoma Cells Causes Apoptosis and Pyroptosis in Both Infected and Bystander Cells.
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DOI：
10.1038/srep37433
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发表时间：
2016-12-15
影响因子：
4.6
通讯作者：
Russell RS
中科院分区：
文献类型：
--
作者：
Kofahi HM;Taylor NG;Hirasawa K;Grant MD;Russell RS
感染丙型肝炎病毒（HCV）的个体处于发展进行性肝病的高风险中，包括肝硬化和肝细胞癌（HCC）。丙型肝炎病毒感染如何导致肝脏破坏多年来一直受到人们的关注，细胞凋亡已被提出作为一种操作机制。在这项研究中，我们采用了一种组织培养适应株的HCV（JFH 1 T），以测试HCV感染对诱导Huh-7.5细胞程序性细胞死亡（PCD）的影响。我们发现，HCV感染降低了增殖率，并诱导caspase-3介导的细胞凋亡的感染细胞群。然而，除了细胞凋亡，我们还观察到受感染的细胞经历胱天蛋白酶-1介导的pyroptosis，这是由NLRP 3炎性小体激活诱导的。通过将HCV感染的Huh-7.5细胞与HCV非允许细胞系共培养，我们还证明了在未感染的细胞中诱导凋亡和焦亡。旁观者凋亡，而不是旁观者pyroptosis，需要感染和旁观者细胞之间的细胞接触。总之，这些发现提供了新的信息，细胞死亡的机制，在响应HCV感染。旁观者细胞既可以诱导凋亡，也可以诱导焦亡，这一观察结果扩展了我们对HCV在肝脏中诱导的发病机制的理解。
Individuals infected with hepatitis C virus (HCV) are at high risk of developing progressive liver disease, including cirrhosis and hepatocellular carcinoma (HCC). How HCV infection causes liver destruction has been of significant interest for many years, and apoptosis has been proposed as one operative mechanism. In this study, we employed a tissue culture-adapted strain of HCV (JFH1T) to test effects of HCV infection on induction of programmed cell death (PCD) in Huh-7.5 cells. We found that HCV infection reduced the proliferation rate and induced caspase-3-mediated apoptosis in the infected cell population. However, in addition to apoptosis, we also observed infected cells undergoing caspase-1-mediated pyroptosis, which was induced by NLRP3 inflammasome activation. By co-culturing HCV-infected Huh-7.5 cells with an HCV-non-permissive cell line, we also demonstrated induction of both apoptosis and pyroptosis in uninfected cells. Bystander apoptosis, but not bystander pyroptosis, required cell-cell contact between infected and bystander cells. In summary, these findings provide new information on mechanisms of cell death in response to HCV infection. The observation that both apoptosis and pyroptosis can be induced in bystander cells extends our understanding of HCV-induced pathogenesis in the liver.
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