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Updated: Apr 20, 2026

Two Methods of Heterokaryon Formation to Discover HCV Restriction Factors
Published on: July 16, 2012
Interferon-inducible cholesterol-25-hydroxylase inhibits hepatitis C virus replication via distinct mechanisms
Yongzhi Chen1, Shanshan Wang2, Zhaohong Yi3
11] CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Chaoyang District, Beijing, China [2] University of Chinese Academy of Sciences, Beijing, China.
Abstract:
Cholesterol 25-hydroxylase (CH25H) as an interferon-stimulated gene (ISG) has recently been shown to exert broad antiviral activity through the production of 25-hydroxycholesterol (25HC), which is believed to inhibit the virus-cell membrane fusion during viral entry. However, little is known about the function of CH25H on HCV infection and replication and whether antiviral function of CH25H is exclusively mediated by 25HC. In the present study, we have found that although 25HC produced by CH25H can inhibit HCV replication, CH25H mutants lacking the hydroxylase activity still carry the antiviral activity against HCV but not other viruses such as MHV-68. Further studies have revealed that CH25H can interact with the NS5A protein of HCV and inhibit its dimer formation, which is essential for HCV replication. Thus, our work has uncovered a novel mechanism by which CH25H restricts HCV replication, suggesting that CH25H inhibits viral infection through both 25HC-dependent and independent events.
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