Phospholipid scramblase 1 mediates hepatitis C virus entry into host cells

Hepatitis C virus (HCV) infects human hepatocytes through several host factors. However, other prerequisite factors for viral entry remain to be identified. Using a yeast two-hybrid screen, we found that human phospholipid scramblase 1 interacts with HCV envelope proteins E1 and E2. These physical interactions were confirmed by co-immunoprecipitation and GST pull-down assays. Knocking down the expression of PLSCR1 inhibited the entry of HCV pseudoparticles. Moreover, PLSCR1 was required for the initial attachment of HCV onto hepatoma cells, where it specifically interacted with entry factor OCLN. We show that PLSCR1 is a novel attachment factor for HCV entry.Structured summary of protein interactionsOCLN physically interacts with PLSCR1 by anti tag coimmunoprecipitation (View interaction)E2 physically interacts with PLSCR1 by anti tag coimmunoprecipitation (View interaction)PLSCR1 physically interacts with E2 by anti tag coimmunoprecipitation (View interaction)PLSCR1 physically interacts with OCLN by anti tag coimmunoprecipitation (View interaction)PLSCR1 physically interacts with E2 by pull down (View interaction)E1 physically interacts with PLSCR1 by two hybrid (View interaction)E2 physically interacts with PLSCR1 by two hybrid (View interaction)PLSCR1 physically interacts with E1 by anti tag coimmunoprecipitation (View interaction)E2 physically interacts with PLSCR1 by pull down (View interaction)E1 physically interacts with PLSCR1 by pull down (View interaction)

► Human phospholipid scramblase 1 interacts with HCV envelope proteins E1 and E2.
► Knockdown the expression of PLSCR1 inhibits the entry of HCV pseudoparticles.
► PLSCR1 is required for the initial attachment of HCV with hepatoma cells.
► PLSCR1 specifically interacts with entry factor OCLN.