Upregulation of HBV transcription by sodium taurocholate cotransporting polypeptide at the postentry step is inhibited by the entry inhibitor Myrcludex B

• Published in: Emerging microbes & infections Vol. 7; no. 1; pp. 1 - 14
• Main Authors: Zhao, Kaitao, Liu, Shuhui, Chen, Yingshan, Yao, Yongxuan, Zhou, Ming, Yuan, Yifei, Wang, Yun, Pei, Rongjuan, Chen, Jizheng, Hu, Xue, Zhou, Yuan, Zhao, He, Lu, Mengji, Wu, Chunchen, Chen, Xinwen
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 21.11.2018; Taylor & Francis Ltd; Nature Publishing Group UK; Taylor & Francis Group
• Subjects: Animals; Antiviral Agents - pharmacology; Bile; Cell Line; DNA, Viral - genetics; Hep G2 Cells; Hepatitis B virus - drug effects; Hepatitis B virus - genetics; Hepatitis B virus - physiology; Hepatocytes - virology; Humans; Lipopeptides - pharmacology; Male; Mice; Mice, Inbred C57BL; Organic Anion Transporters, Sodium-Dependent - genetics; Polypeptides; Promoter Regions, Genetic; Real-Time Polymerase Chain Reaction; Receptors, Cytoplasmic and Nuclear - genetics; Symporters - genetics; Transcriptional Activation; Up-Regulation; Virus Internalization - drug effects
• ISSN: 2222-1751; 2222-1751
• DOI: 10.1038/s41426-018-0189-8

Sodium taurocholate cotransporting polypeptide (NTCP) is a functional receptor for hepatitis B virus (HBV) entry. However, little is known regarding whether NTCP is involved in regulating the postentry steps of the HBV life cycle. Here, we found that NTCP expression upregulated HBV transcription at the postentry step and that the NTCP-targeting entry inhibitor Myrcludex B (MyrB) effectively suppressed HBV transcription both in an HBV in vitro infection system and in mice hydrodynamically injected with an HBV expression plasmid. Mechanistically, NTCP upregulated HBV transcription via farnesoid X receptor α (FxRα)-mediated activation of the HBV EN2/core promoter at the postentry step in a manner that was dependent on the bile acid (BA)-transport function of NTCP, which was blocked by MyrB. Our findings uncover a novel role for NTCP in the HBV life cycle and provide a reference for the use of novel NTCP-targeting entry inhibitors to suppress HBV infection and replication.