RT Journal Article
SR Electronic
T1 Functional microRNA screen uncovers O-linked N-acetylglucosamine transferase as a host factor modulating hepatitis C virus morphogenesis and infectivity
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 380
OP 392
DO 10.1136/gutjnl-2018-317423
VO 69
IS 2
A1 Katharina Herzog
A1 Simonetta Bandiera
A1 Sophie Pernot
A1 Catherine Fauvelle
A1 Frank Jühling
A1 Amélie Weiss
A1 Anne Bull
A1 Sarah C Durand
A1 Béatrice Chane-Woon-Ming
A1 Sébastien Pfeffer
A1 Marion Mercey
A1 Hervé Lerat
A1 Jean-Christophe Meunier
A1 Wolfgang Raffelsberger
A1 Laurent Brino
A1 Thomas F Baumert
A1 Mirjam B Zeisel
YR 2020
UL http://gut.bmj.com/content/69/2/380.abstract
AB Objective Infection of human hepatocytes by the hepatitis C virus (HCV) is a multistep process involving both viral and host factors. microRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. Given that miRNAs were indicated to regulate between 30% and 75% of all human genes, we aimed to investigate the functional and regulatory role of miRNAs for the HCV life cycle.Design To systematically reveal human miRNAs affecting the HCV life cycle, we performed a two-step functional high-throughput miRNA mimic screen in Huh7.5.1 cells infected with recombinant cell culture-derived HCV. miRNA targeting was then assessed using a combination of computational and functional approaches.Results We uncovered miR-501-3p and miR-619-3p as novel modulators of HCV assembly/release. We discovered that these miRNAs regulate O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression and identified OGT and O-GlcNAcylation as regulators of HCV morphogenesis and infectivity. Furthermore, increased OGT expression in patient-derived liver tissue was associated with HCV-induced liver disease and cancer.Conclusion miR-501-3p and miR-619-3p and their target OGT are previously undiscovered regulatory host factors for HCV assembly and infectivity. In addition to its effect on HCV morphogenesis, OGT may play a role in HCV-induced liver disease and hepatocarcinogenesis.