Type I Interferon Responses to Hepatitis C Virus

描述（由申请人提供）：丙型肝炎病毒是一种单链RNA病毒，全世界有1.7亿人感染丙型肝炎病毒，西班牙裔人群感染丙型肝炎病毒的风险更高。事实上，西班牙裔与慢性丙型肝炎感染的侵袭性病程有关。在大约80%的感染者中，它会导致慢性肝病和癌症。目前，尚无疫苗可用，目前治疗这种病毒的疗法价格昂贵，时间长（6-12个月），伴有明显的副作用，并且只有50%的患者能产生持续的病毒反应。丙型肝炎病毒研究的基本问题是病毒如何在没有全面性免疫缺陷的宿主中建立持久和多产的感染。对这个问题的回答可能会导致对病毒如何在免疫能力强的宿主中持续存在的理解。一个基本的假设是，HCV已经发展出了逃避宿主免疫反应的策略。本研究的目的是阐明细胞内先天抗病毒免疫在丙型肝炎病毒和宿主细胞共同进化中的作用。如果我们的中心假设是正确的，我们应该能够测试新的方法来改变慢性感染背景下HCV和肝细胞之间的平衡，从而增强肝细胞的先天免疫防御，从而从人类宿主中消除HCV。

DESCRIPTION (provided by applicant): Hepatitis C Virus is a single stranded RNA virus that infects 170 million people world wide and the risk of contracting HCV is higher in Hispanics individuals. In fact, Hispanics are Associated with an aggressive course of Chronic Hepatitis C Infection. It causes chronic liver disease and cancer in approximately 80 % of infected individuals. Currently, there is no vaccine available and current therapies to treat this virus are costly, lengthy (6-12 months), associated with significant side effects, and result in sustained viral response by only 50% of the patients. The fundamental question in HCV research is how the virus establishes a persistent and productive infection in the host where there is no generalized immune deficiency. Answers to this question may lead to an understanding of how the virus persists in an immunocompetent host. A basic hypothesis is that HCV has developed strategies to evade the host's immune responses. The objective of this proposal is to elucidate the role of intracellular innate antiviral immunity in the co-evolution of HCV and host cells. If our central hypothesis is correct, we should be able to test novel approaches to shift the balance between HCV and hepatocytes in the setting of chronic infection toward an enhanced hepatocyte innate immune defense resulting in elimination of HCV from the human host.