Upregulation of HBV transcription by sodium taurocholate cotransporting polypeptide at the postentry step is inhibited by the entry inhibitor Myrcludex B.
Emerg Microbes Infect
; 7(1): 186, 2018 Nov 21.
Article
em En
| MEDLINE
| ID: mdl-30459339
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Ativação Transcricional
/
Vírus da Hepatite B
/
Transportadores de Ânions Orgânicos Dependentes de Sódio
/
Simportadores
/
Internalização do Vírus
/
Lipopeptídeos
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article