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牛磺胆酸钠共转运蛋白介导绒猴乙型肝炎病毒感染食蟹猴肝细胞。

Sodium taurocholate cotransporting polypeptide mediates woolly monkey hepatitis B virus infection of Tupaia hepatocytes.

机构信息

National Institute of Biological Sciences, Beijing, China.

出版信息

J Virol. 2013 Jun;87(12):7176-84. doi: 10.1128/JVI.03533-12. Epub 2013 Apr 17.

Abstract

Primary Tupaia hepatocytes (PTHs) are susceptible to woolly monkey hepatitis B virus (WMHBV) infection, but the identity of the cellular receptor(s) mediating WMHBV infection of PTHs remains unclear. Recently, sodium taurocholate cotransporting polypeptide (NTCP) was identified as a functional receptor for human hepatitis B virus (HBV) infection of primary human and Tupaia hepatocytes. In this study, a synthetic pre-S1 peptide from WMHBV was found to bind specifically to cells expressing Tupaia NTCP (tsNTCP) and it efficiently blocked WMHBV entry into PTHs; silencing of tsNTCP in PTHs significantly inhibited WMHBV infection. Ectopic expression of tsNTCP rendered HepG2 cells susceptible to WMHBV infection. These data demonstrate that tsNTCP is a functional receptor for WMHBV infection of PTHs. The result also indicates that NTCP's orthologs likely act as a common cellular receptor for all known primate hepadnaviruses.

摘要

原代食蟹猴肝细胞(PTHs)易感染绒猴乙型肝炎病毒(WMHBV),但介导 WMHBV 感染 PTHs 的细胞受体(s)的身份仍不清楚。最近,牛磺胆酸钠共转运蛋白(NTCP)被鉴定为人类乙型肝炎病毒(HBV)感染原代人和食蟹猴肝细胞的功能受体。在这项研究中,发现 WMHBV 的合成前 S1 肽特异性结合表达食蟹猴 NTCP(tsNTCP)的细胞,并且有效地阻止 WMHBV 进入 PTHs;在 PTHs 中沉默 tsNTCP 可显著抑制 WMHBV 感染。tsNTCP 的异位表达使 HepG2 细胞易感染 WMHBV。这些数据表明 tsNTCP 是 PTHs 感染 WMHBV 的功能受体。该结果还表明,NTCP 的同源物可能作为所有已知灵长类动物嗜肝病毒的共同细胞受体发挥作用。

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