Mouse homologues of hepatitis C virus human entry factors inhibit the entry of HCV pseudo-particles (HCVpp) into human hepatoma cells

Abstract

Hepatitis C virus (HCV) is a growing public health concern worldwide. No vaccine preventing HCV has yet been developed due to the hindrance of research on suitable small animal models. Moreover, it was known that human CD81, claudin[1]1 (CLDN1), scavenger receptor type B class I (SCARB1) and occludin (OCLN) (collectively called CCSO) are important factors for HCV entry into human hepatocytes. Therefore, we previously generated transgenic mice expressing CCSO in their hepatocytes, but these mice do not confer susceptibility to HCVpp or HCV entry. Earlier study also showed mouse hepatocytes had strong restriction factor(s) that inhibit HCV entry. Here, we tried to find out the inhibitory factor(s), and found mouse homologues (Cd81, Ocln) themselves are inhibitory for HCV entry in human hepatoma cells when they express the mouse homologues on their cell surfaces. So, deleting these inhibitory factors can make mouse hepatocytes more susceptible to HCV infectivity in vivo. This in vitro study would thus be helpful in making an efficient mouse model for HCV infection.