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（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结果。I型干扰素β（IFN-β）系统在病毒感染后被迅速诱导，并在先天免疫中起核心作用。干扰素调节因子-3（interferon regulatory factor-3，IRF-3）作为宿主第一道防线被I型干扰素诱导后立即磷酸化，形成同源二聚体并移位至细胞核。在表达HCV全基因组（HCR 6-Rz）后，由新城堡病病毒（NDV）引起的IFN-β诱导显著降低。在表达核心至NS 2蛋白区域（HCR 6-Fse）的细胞系中观察到类似的修饰。然而，在表达NS 2至NS 5 B区域的细胞系（HCR 6-Age）中未观察到这种降低。HCR 6-Rz和HCR 6-Fse表达后，NDV感染诱导的IRF-3二聚体形成也受到抑制，但HCR 6-Age不表达。我们进一步分析使用瞬时表达的HCV核心，E1或E2在HepG 2细胞。IRF-3二聚体形成的抑制由HCV核心蛋白单独引起。这些结果提示HCV核心蛋白可能具有一种新的重要生物学功能，可能与HCV的持续存在和致病有关。

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.