Hepatic cells derived from induced pluripotent stem cells of pigtail macaques support hepatitis C virus infection

Abstract

The narrow species tropism of hepatitis C virus (HCV) limits animal studies. We found that pigtail macaque (Macaca nemestrina) hepatic cells derived from induced pluripotent stem cells support the entire HCV life cycle, although infection efficiency was limited by defects in the HCV cell entry process. This block was overcome by either increasing occludin expression, complementing the cells with human CD81, or infecting them with a strain of HCV with less restricted requirements for CD81. Using this system, we can modify viral and host cell genetics to make pigtail macaques a suitable, clinically relevant model for the study of HCV infection.

Keywords: 2′C-methyl-adenosine; 2′CMA; Animal Model; GLuc; Gaussia luciferase; HCV; HCVcc; HCVpp; Hepatitis C Virus; Macaca nemestrina; Macaca nemestrina induced pluripotent stem cells; Macaca nemestrina–derived hepatocyte-like cells; Mn; MnHep; MniPSC; Monkey; OCLN; Replication; VSVGpp; cell culture–derived hepatitis C virus; hepatitis C virus; hepatitis C virus pseudoparticles; occludin; vesicular stomatitis virus glycoprotein.