From DCPD to NTCP: the long journey towards identifying a functional hepatitis B virus receptor.
From DCPD to NTCP: the long journey towards identifying a functional hepatitis B virus receptor.
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DOI：
10.3350/cmh.2015.21.3.193
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发表时间：
2015-09
影响因子：
8.9
通讯作者：
Tong S
中科院分区：
文献类型：
--
作者：
Li J;Tong S
B型肝炎病毒（HBV）是嗜肝DNA病毒（嗜肝DNA病毒）的原型，感染广泛的人类和非人类宿主。鸭肝炎B病毒（DHBV）的前期研究发现，鸭羧肽酶D（dCPD）是全长大包膜蛋白的宿主特异性结合伴侣，p120是几种截短型大包膜蛋白的结合伴侣。p120是鸭甘氨酸脱羧酶（dGLDC）的P蛋白，在鸭乙型肝炎病毒（DHBV）感染的组织中限制性表达。尽管dCPD和p120 cDNA都不能在任何细胞系中赋予DHBV感染的易感性，但一些证据表明dCPD，尤其是p120在生产性DHBV感染中的重要性。最近，牛磺胆酸钠共转运多肽（NTCP）已被确定为HBV大包膜蛋白N-末端的结合伴侣。重要的是，敲除和重建实验明确表明，NTCP是HBV和丁型肝炎病毒（HDV）（一种使用HBV包膜蛋白进行传播的RNA病毒）体外感染的必要和充分条件。目前尚不清楚NTCP是否是体内主要的HBV受体。事实上，一些HBV患者是纯合子与NTCP突变，已知取消其受体功能，表明存在的NTCP非依赖性途径的HBV进入。此外，NTCP很可能仅介导HBV进入过程的一个步骤，而生产性HBV感染的其他辅助因子仍有待发现。NTCP为控制慢性HBV感染提供了新的治疗靶点。
Hepatitis B virus (HBV) is the prototype of hepatotropic DNA viruses (hepadnaviruses) infecting a wide range of human and non-human hosts. Previous studies with duck hepatitis B virus (DHBV) identified duck carboxypeptidase D (dCPD) as a host specific binding partner for full-length large envelope protein, and p120 as a binding partner for several truncated versions of the large envelope protein. p120 is the P protein of duck glycine decarboxylase (dGLDC) with restricted expression in DHBV infectible tissues. Several lines of evidence suggest the importance of dCPD, and especially p120, in productive DHBV infection, although neither dCPD nor p120 cDNA could confer susceptibility to DHBV infection in any cell line. Recently, sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a binding partner for the N-terminus of HBV large envelope protein. Importantly, knock down and reconstitution experiments unequivocally demonstrated that NTCP is both necessary and sufficient for in vitro infection by HBV and hepatitis delta virus (HDV), an RNA virus using HBV envelope proteins for its transmission. What remains unclear is whether NTCP is the major HBV receptor in vivo. The fact that some HBV patients are homozygous with an NTCP mutation known to abolish its receptor function suggests the existence of NTCP-independent pathways of HBV entry. Also, NTCP very likely mediates just one step of the HBV entry process, with additional co-factors for productive HBV infection still to be discovered. NTCP offers a novel therapeutic target for the control of chronic HBV infection.