1. Academic Validation
  2. Upregulation of HBV transcription by sodium taurocholate cotransporting polypeptide at the postentry step is inhibited by the entry inhibitor Myrcludex B

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

  • Emerg Microbes Infect. 2018 Nov 21;7(1):186. doi: 10.1038/s41426-018-0189-8.
Kaitao Zhao 1 2 Shuhui Liu 1 2 Yingshan Chen 1 2 Yongxuan Yao 1 2 Ming Zhou 3 Yifei Yuan 1 2 Yun Wang 1 Rongjuan Pei 1 Jizheng Chen 1 Xue Hu 1 Yuan Zhou 1 He Zhao 1 Mengji Lu 4 Chunchen Wu 5 Xinwen Chen 6 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, 430071, Wuhan, China.
  • 2 University of Chinese Academy of Sciences, 100049, Beijing, China.
  • 3 Shenzhen Xenotransplantation Research and Development Center, State and Local Joint Cancer Genome Clinical Application of Key Technology Laboratory, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, 518035, Shenzhen, China.
  • 4 Institute of Virology, University Hospital of Essen, 45147, Essen, Germany.
  • 5 State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, 430071, Wuhan, China. wucc@wh.iov.cn.
  • 6 State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, 430071, Wuhan, China. chenxw@wh.iov.cn.
  • 7 University of Chinese Academy of Sciences, 100049, Beijing, China. chenxw@wh.iov.cn.
Abstract

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.

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