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Impairment of the dimer formation of interferon regulatory factor-3 by hepatitis C virus core protein leads to evade interferon system

丙型肝炎病毒核心蛋白损害干扰素调节因子3二聚体形成导致逃避干扰素系统

基本信息

批准号：
14370106
负责人：
KOHARA Michinori
金额：
$ 8.9万
依托单位：
Tokyo Metropolitan Organization for Medical Research
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370106/
关键词：
Hepatitis C Virus Interferon IRF-3 Persistent infection Dimer formation

项目摘要

One of the prominent features of hepatitis C virus (HCV) is persistent infection, which is assumed to be a crucial event as a result of evading host defense system. Type I interferon beta (IFN-β) system is induced rapidly after viral infection and plays a central role in innate immunity. Upon immediate induction of type I IFN as host first defense line, interferon regulatory factor-3 (IRF-3) is phosphorylated, formed of homodimer and translocates to nucleus. IFN-β induction due to new castle disease virus (NDV) was significantly decreased after the expression of full HCV genome (HCR6-Rz). Similar modification was observed in cell line expressing core to the NS2 protein region (HCR6-Fse). However, this decreasing was not observed in cell line expressing NS2 to the NS5B region (HCR6-Age). IRF-3 dimer formation induced by NDV infection was also suppressed after the expression of HCR6-Rz and HCR6-Fse, but not HCR6-Age. We further analyzed using transiently expressed HCV core, E1 or E2 in HepG2 cells. The suppression of IRF-3 dimer formation was caused by HCV core protein alone. These results indicated that a new crucial biological function of HCV core protein that may be related to persistence and pathogenesis of HCV.

丙型肝炎病毒(HCV)的显著特征之一是持续感染，这被认为是逃避宿主防御系统的关键事件。I型干扰素-β(I型干扰素-β)系统在病毒感染后迅速诱导，在天然免疫中起核心作用。在诱导型干扰素作为宿主第一防线后，干扰素调节因子-3(IRF-3)被磷酸化，形成同源二聚体，并移位到细胞核。新城疫病毒诱导的干扰素-β在丙型肝炎病毒全基因组(HCR6Rz)表达后显著降低。在表达核心到NS2蛋白区域的细胞系(HCR6-FSE)中也观察到类似的修饰。然而，在表达NS2至NS5B区的细胞系(HCR6-AGE)中并未观察到这种减少。新城疫病毒感染诱导的IRF-3二聚体的形成在HCR6-Rz和HCR6-FSE表达后也受到抑制，但不能抑制HCR6-Age的表达。我们进一步分析了在HepG2细胞中瞬时表达的丙型肝炎病毒核心蛋白E1或E2。抑制IRF-3二聚体的形成是由丙型肝炎病毒核心蛋白单独作用引起的。这些结果表明，丙型肝炎病毒核心蛋白的一个新的重要生物学功能可能与丙型肝炎病毒的持久性和致病机制有关。