Moorman Jonathan P, Prayther Deborah, McVay Derek, Hahn Young S, Hahn Chang S
Department of Internal Medicine, East Tennessee State University, James H. Quillen College of Medicine, Johnson City, TN 37614, USA.
Virology. 2003 Aug 1;312(2):320-9. doi: 10.1016/s0042-6822(03)00208-3.
Hepatitis C virus (HCV) is remarkable for its ability to establish persistent infection. Studies suggest that HCV core protein modulates immune responses to viral infection and can bind Fas receptor in vitro. To further examine the role of HCV core protein in Fas signaling, full-length (aa 1-192) and truncated (aa 1-152) HCV core proteins were expressed in Jurkat lymphocytes and cells were assayed for apoptotic response, caspase activation, and Fas activation. Jurkat expressing full-length but not truncated core protein exhibited ligand-independent apoptosis. Cytoplasmic targeting of truncated core protein recapitulated its ability to induce apoptosis. Activation of caspases 8 and 3 was necessary and sufficient for full-length core to induce apoptosis. Jurkat cells expressing full-length but not truncated core protein induced Fas receptor aggregation. HCV core activates apoptotic pathways in Jurkat via Fas and requires cytoplasmic localization of core. Infection of host lymphocytes by HCV may alter apoptotic signaling and skew host responses to acute infection.
丙型肝炎病毒（HCV）以其建立持续感染的能力而著称。研究表明，HCV核心蛋白可调节对病毒感染的免疫反应，并且在体外能与Fas受体结合。为了进一步研究HCV核心蛋白在Fas信号传导中的作用，在Jurkat淋巴细胞中表达了全长（第1至192位氨基酸）和截短（第1至152位氨基酸）的HCV核心蛋白，并检测细胞的凋亡反应、半胱天冬酶激活及Fas激活情况。表达全长而非截短核心蛋白的Jurkat细胞表现出不依赖配体的凋亡。截短核心蛋白的胞质靶向作用重现了其诱导凋亡的能力。半胱天冬酶8和3的激活对于全长核心蛋白诱导凋亡是必需且充分的。表达全长而非截短核心蛋白的Jurkat细胞诱导了Fas受体聚集。HCV核心蛋白通过Fas在Jurkat细胞中激活凋亡途径，且核心蛋白需要定位于胞质。HCV感染宿主淋巴细胞可能会改变凋亡信号传导，并使宿主对急性感染的反应发生偏差。
