a concerted action of hepatitis c virus p7 and nonstructural protein 2 regulates core localization at the endoplasmic reticulum and virus assembly丙型肝炎病毒p7的协调一致的行动和非结构蛋白2调节的核心定位在内质网和病毒组装.pdfVIP

A Concerted Action of Hepatitis C Virus P7 and Nonstructural Protein 2 Regulates Core Localization at the Endoplasmic Reticulum and Virus Assembly 1,2,3 ´ 1,2,3 4 ¨ 1,2,3 Bertrand Boson , Ophelia Granio , Ralf Bartenschlager , Franc¸ois-Loıc Cosset * ´ ´ 1 Universite de Lyon, Lyon, France, 2 INSERM, U758, Lyon, France, 3 Ecole Normale Superieure de Lyon, Lyon, France, 4 Department of Infectious Diseases, Molecular Virology, University of Heidelberg, Heidelberg, Germany Abstract Hepatitis C virus (HCV) assembly remains a poorly understood process. Lipid droplets (LDs) are thought to act as platforms for the assembly of viral components. The JFH1 HCV strain replicates and assembles in association with LD-associated membranes, around which viral core protein is predominantly detected. In contrast, despite its intrinsic capacity to localize to LDs when expressed individually, we found that the core protein of the high-titer Jc1 recombinant virus was hardly detected on LDs of cell culture-grown HCV (HCVcc)-infected cells, but was mainly localized at endoplasmic reticulum (ER) membranes where it colocalized with the HCV envelope glycoproteins. Furthermore, high-titer cell culture-adapted JFH1 virus, obtained after long-term culture in Huh7.5 cells, exhibited an ER-localized core in contrast to non-adapted JFH1 virus, strengthening the hypothesis that ER localization of core is required for efficient HCV assembly. Our results further indicate that p7 and NS2 are HCV strain-specific factors that govern the recruitment of core protein from LDs to ER assembly sites. Indeed, using expression