Hepatitis C virus and intracellular antiviral

丙型肝炎病毒（HCV）是一种新兴的传染病。接触这种病毒的患者往往不能 清除这种病毒感染并成为慢性携带者。这种病毒的慢性感染可导致严重的肝脏 包括肝硬化和肝细胞癌的疾病。丙型肝炎病毒如何逃避宿主免疫建立 然而，慢性感染在很大程度上仍不清楚。近年来的研究表明，HCV可以抑制 细胞内抗病毒反应。本研究项目的目标是进一步研究HCV如何相互作用 以逃避细胞内的先天免疫。RIG-I是一种重要的模式识别受体 (PRR)它的激活可以导致一系列的抗病毒反应。最近的研究表明 HCV可以破坏RIG-I信号传导。因此，本项目具体目标1的目标是进一步调查 HCV和RIG-I信号传导之间的相互作用。PKR是一种双链RNA依赖性蛋白激酶。它 是细胞中另一个重要的PRR。它的激活将导致翻译起始因子的失活 eIF 2 α用于抑制细胞和病毒蛋白质合成。我们最近的研究表明， 可以诱导eIF 2 α的磷酸化，这似乎不抑制HCV复制。因此 具体目标2的目的是进一步研究PKR和eIF 2 α在抗HCV应答中的作用。 自噬是天然免疫的重要组成部分。它可以清除细胞内的病原体包括病毒 并且对于将胞质病毒RNA递送到内体以激活Toll样受体7也是关键的 （TLR7）。我们最近的研究表明，HCV可以抑制自噬体和 内体/溶酶体。HCV对宿主细胞的这种作用可能对于防止HCV的激活是重要的。 TLR7。具体目标3的目标是进一步研究HCV如何干扰自噬途径， 研究这种扰动对TLR 7激活的可能影响。 本项目的研究将有助于更好地了解HCV与宿主的相互作用 细胞因此，它将有助于本计划，以提高对宿主细胞如何控制的理解， 病毒复制以及病毒如何抑制细胞内的抗病毒防御。

Hepatitis C virus (HCV) is an emerging infectious disease. Patients exposed to this virus frequently fail to clear this viral infection and become chronic carriers. Chronic infection by this virus can lead to severe liver diseases including cirrhosis and hepatocellular carinoma. How HCV evades host immunity to establish chronic infection, however, remains largely unclear. Studies in recent years indicate that HCV can suppress intracellular antiviral responses. The goal of this research project is to further investigate how HCV interacts with its host cells to evade intracellular innate immunity. RIG-I is an important pattern recognition receptor (PRR) in cells and its activation can lead to a cascade of antiviral responses. Recent studies indicate that HCV can disrupt RIG-I signaling. Thus, the goal of specific aim 1 of this project is to further investigate the interactions between HCV and RIG-I signaling. PKR is a double-stranded RNA dependent protein kinase. It is another important PRR in cells. Its activation will result in the inactivation of the translation initiation factor elF2alpha for the suppression of cellular and viral protein synsthesis. Our recent studies indicate that HCV could induce the phophorylation of elF2alpha, which does not appear to suppress HCV replication. Thus, the goal of specific aim 2 is to further investigate the role of PKR and elF2alpha in anti-HCV response. Autophagy is an important arm of innate immunity. It can remove intracellular pathogens including viruses and is also critical for delivering cytosolic viral RNA to endosomes for the activation of toll-like receptor 7 (TLR7). Our recent studies indicated that HCV could suppress the fusion between autophagosomes and endosomes/lysosomes. This effect of HCV on host cells may be important for preventing the activation of TLR7. The goal of specific aim 3 is to further investigate how HCV perturbs the autophagic pathway and to study the possible effect of this perturbation on the activation of TLR7. The research of this project will lead to a better understanding of the interaction between HCV and its host cells. Thus, it will contribute positively to this Program to enhance the understanding of how host cells control viral replication and how viruses suppress intracellular antiviral defenses.