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Researchers at Institut Pasteur of Shanghai discoveranew mechanism for restricting Hepatitis C Virusinfection by host innate immunity

Hepatitis C virus (HCV) is an important human pathogen that causes chronic liver diseases including hepatitis, liver cirrhosis and hepatocellular carcinoma. The tremendous progress has been achieved in the therapeutics of HCV thanks to the development of direct antiviral agents, but the worldwide application of these antiviral agents is limited due to the high cost. Furthermore, no vaccine is available for preventing new HCV infection. Therefore, HCV still imposes a big threat to human public health.

Yu Xiang, the first author of the paper and aPh.D. student in Prof. Jin Zhong’s laboratory at Institut Pasteur of Shanghai, Chinese Academy of Sciences, discovered 25-hydroxychelsterol (25HC) and its synthesizing enzyme cholesterol-25-hydroxylase (CH25H) efficiently inhibit HCV infection. CH25H inhibits HCV infection by suppressing the maturation of SREBPs, critical transcription factors for host lipid biosynthesis. Interestingly, CH25H constitutes a part of host innate immune response against virus infection. In contrast to studies in mice, CH25H is not induced by interferons, but rather represents a primary and direct host response to viral infection. This study shed light on the function of CH25H in controlling HCV infection and shall provide a new strategy for anti-HCV therapeutics.

This paper entitled “Identification of cholesterol-25-hydroxylase as a novel host restriction factor as a part of primary innate immune responses against hepatitis C virus infection”waspublished online by Journal of Virology on April 22, 2015.

This study was performed in collaboration with Prof.Bao-Liang Song’s group at Wuhan University, and supported by grants from the National Natural ScienceFoundation of China, the Chinese National 973 Program and the Chinese National Science and Technology Mega Projects on Major Infectious Diseases.

Link for this article: http://www.ncbi.nlm.nih.gov/pubmed/25903345

A. 25HC inhibits HCV infection. B. CH25H is up-regulated upon HCV infection. C. CH25H knockdown promotes HCV infection.

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