Li Jisu, Tong Shuping
Liver Research Center, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, USA.
Liver Research Center, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, USA. ; Key lab of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Clin Mol Hepatol. 2015 Sep;21(3):193-9. doi: 10.3350/cmh.2015.21.3.193. Epub 2015 Sep 30.
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.
乙型肝炎病毒（HBV）是嗜肝DNA病毒（嗜肝病毒）的原型，可感染广泛的人类和非人类宿主。先前对鸭乙型肝炎病毒（DHBV）的研究确定鸭羧肽酶D（dCPD）为全长大包膜蛋白的宿主特异性结合伴侣，而p120为大包膜蛋白几个截短版本的结合伴侣。p120是鸭甘氨酸脱羧酶（dGLDC）的P蛋白，在DHBV可感染组织中表达受限。多项证据表明dCPD，尤其是p120在DHBV的有效感染中具有重要作用，尽管dCPD和p120的cDNA均不能使任何细胞系对DHBV感染敏感。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端的结合伴侣。重要的是，敲低和重组实验明确证明NTCP对于HBV和丁型肝炎病毒（HDV，一种利用HBV包膜蛋白进行传播的RNA病毒）的体外感染既是必需的也是充分的。尚不清楚的是NTCP是否是体内主要的HBV受体。一些HBV患者是已知可消除其受体功能的NTCP突变的纯合子，这一事实表明存在不依赖NTCP的HBV进入途径。此外，NTCP很可能仅介导HBV进入过程的一个步骤，仍有待发现其他有助于HBV有效感染的辅助因子。NTCP为控制慢性HBV感染提供了一个新的治疗靶点。
