[转移贴]讨论：为什么至今仍未发现HBV的受体？
原贴由applechan发表于 2007-9-14 23:42从上个世纪七十年代分离出HBV已经有好几十年了，而且各国特别是中国投了不少钱在里面，为什么至今仍对HBV的受体不确定？ 我容易吗我发表于 2007-9-15 16:18：
复旦大学生化与分子生物学实验室HBV受体的研究：
乙肝是中国人的重大疾病之一。但是到目前为止还没有确定乙肝病毒在肝脏细胞上的受体，这是因为受体是一个蛋白质复合体，用一般的分子生物学手段很难将一个复合体加以确定。我们在将各种手段进行综合，力图确定这个复合物。
http://www.hwdlab.net/show_hdr.php?xname=PSMF77K&dname=50CI221&xpos=0 bigben发表于 2008-1-8 20:29 ：
关于HBV受体最新的研究是发现了一个低亲和力的受体：硫酸乙酰肝素糖蛋白(heparan sulfate proteoglycans,HSPG)，高亲和力受体没有找到，结果发表在2008年Cell Microbiol上，是由德国吉森大学(Justus-Liebig-University Giessen)的一个研究组做的
标题: Role of glycosaminoglycans for binding and infection of hepatitis B virus.
作者: Leistner, C. M.; Gruen-Bernhard, S.; Glebe, D.
来源: Cell Microbiol, 2008, 10(1): 122-133
摘要:
Many parts of the life cycle of hepatitis B virus (HBV) infection of hepatocytes have been unravelled, but the attachment and entry process leading to infection is largely unknown. Using primary Tupaia hepatocyte cultures as an in vitro infection system, we determined that HBV uses cell-surface heparan sulfate proteoglycans as low-affinity receptor, because HBV infection was inhibited by heparin (IC50: 5 microg ml(-1)) or other higher-sulfated polymers, but not by lower-sulfated glycosaminoglycans, such as chondroitin sulfate. Pretreatment of primary hepatocytes with heparinase decreased viral binding and inhibited HBV infection completely. Interestingly, after preS1-dependent viral binding at 16 degrees C to the cell surface, subsequent infection could still be inhibited by HBV preS1-lipopeptides, but not by heparin any more, suggesting a shift of the virus to a high-affinity receptor. In summary, we suggest following multistep attachment process: in vivo, HBV is initially trapped within the liver in the space of Disse by heparan sulfate proteoglycans. Thereafter, HBV binds via its preS1 attachment site and the N-terminal myristic acid to a yet unknown, high-affinity receptor that confers uptake in a yet unknown compartment.
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国内生化所现上医医学分子病毒实验室谢幼华老师组发现一个脂蛋白脂酶(lipoprotein lipase, LPL)可能在介导HBV与“HBV受体”（未发现）之间作用起重要作用
标题: Identification and characterization of peptides that interact with hepatitis B virus via the putative receptor binding site.
作者: Deng, Q.; Zhai, J. W.; Michel, M. L. (...)
来源: J Virol, 2007, 81(8): 4244-4254
摘要:
A direct involvement of the PreS domain of the hepatitis B virus (HBV) large envelope protein, and in particular amino acid residues 21 to 47, in virus attachment to hepatocytes has been suggested by many previous studies. Several PreS-interacting proteins have been identified. However, they share few common sequence motifs, and a bona fide cellular receptor for HBV remains elusive. In this study, we aimed to identify PreS-interacting motifs and to search for novel HBV-interacting proteins and the long-sought receptor. PreS fusion proteins were used as baits to screen a phage display library of random peptides. A group of PreS-binding peptides were obtained. These peptides could bind to amino acids 21 to 47 of PreS1 and shared a linear motif (W1T2X3W4W5) sufficient for binding specifically to PreS and viral particles. Several human proteins with such a motif were identified through BLAST search. Analysis of their biochemical and structural properties suggested that lipoprotein lipase (LPL), a key enzyme in lipoprotein metabolism, might interact with PreS and HBV particles. The interaction of HBV with LPL was demonstrated by in vitro binding, virus capture, and cell attachment assays. These findings suggest that LPL may play a role in the initiation of HBV infection. Identification of peptides and protein ligands corresponding to LPL that bind to the HBV envelope will offer new therapeutic strategies against HBV infection.
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