Type I Interferon Responses to Hepatitis C Virus

I 型干扰素对丙型肝炎病毒的反应

• 批准号: 7488093
• 负责人: ERIKA Adriana EKSIOGLU
• 金额: $ 3.19万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7488093
• 关键词: Acute; Adverse effects; Aggressive course; Antiviral Agents; Apoptosis; Attenuated; Biochemical Genetics; Biological; Cell Culture System; Cell Line; Cells; Chronic; Chronic Hepatitis C; Clone Cells; Coculture Techniques; Contracts; Cultured Cells; Data; Doctor of Philosophy; Equilibrium; Evolution; Experimental Models; Fellowship; GPRC5C gene; Goals; Hepatitis C; Hepatitis C virus; Hepatocyte; Hispanics; Human; Immune; Immune response; Immune system; Immunity; Immunocompetent; Individual; Infection; Interferon Type I; Interferons; Investigation; Knowledge; Laboratories; Lead; Life Cycle Stages; Light; Liver diseases; Liver neoplasms; Malignant Neoplasms; Malignant neoplasm of liver; Modeling; Molecular; Natural Immunity; Outcomes Research; Pathogenesis; Patients; Phenotype; Predoctoral Individual National Research Service Award; Preventive; Production; Proteins; Public Health; RNA; RNA Viruses; Research; Resistance; Ribavirin; Risk; Role; Series; Signal Pathway; System; Testing; Vaccines; Viral; Virus; Virus Diseases; Work; Writing; base; design; eIF-2 Kinase; hepatoma cell; human TLR3 protein; insight; mutant; neoplastic cell; novel; novel strategies; particle; research study; response; tool

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.

描述（由申请人提供）：丙型肝炎病毒是一种单链RNA病毒，感染全球1.7亿人，西班牙裔个体感染HCV的风险较高。事实上，西班牙裔与慢性丙型肝炎感染的侵袭性过程有关。它导致慢性肝病和癌症在大约80%的感染个体.目前，没有可用的疫苗，并且目前治疗这种病毒的疗法是昂贵的、漫长的（6-12个月），与显著的副作用相关，并且仅导致50%的患者的持续病毒应答。HCV研究中的基本问题是病毒如何在没有全身性免疫缺陷的宿主中建立持续和生产性感染。这个问题的答案可能会导致理解病毒如何在免疫活性宿主中持续存在。一个基本的假设是，HCV已经发展出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性抗病毒免疫在HCV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HCV和肝细胞之间的平衡，在慢性感染的设置对增强肝细胞先天免疫防御，从而消除HCV从人类宿主。