Leistner Corinna M, Gruen-Bernhard Stefanie, Glebe Dieter
Institute of Medical Virology, Justus Liebig University, Frankfurter Str. 107, 35392 Giessen, Germany.
Cell Microbiol. 2008 Jan;10(1):122-33. doi: 10.1111/j.1462-5822.2007.01023.x.
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 Dissé 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.
乙型肝炎病毒（HBV）感染肝细胞生命周期的许多环节已被阐明，但导致感染的附着和进入过程仍不清楚。我们使用原代树鼩肝细胞培养物作为体外感染系统，确定HBV将细胞表面硫酸乙酰肝素蛋白聚糖用作低亲和力受体，因为HBV感染受到肝素（IC50：5μg/ml（-1））或其他高硫酸化聚合物的抑制，但不受低硫酸化糖胺聚糖（如硫酸软骨素）的抑制。用肝素酶预处理原代肝细胞可减少病毒结合并完全抑制HBV感染。有趣的是，在16℃下preS1依赖性病毒与细胞表面结合后，随后的感染仍可被HBV preS1脂肽抑制，但不再受肝素抑制，这表明病毒已转变为高亲和力受体。总之，我们提出以下多步骤附着过程：在体内，HBV最初被硫酸乙酰肝素蛋白聚糖捕获在狄氏间隙的肝脏内。此后，HBV通过其preS1附着位点和N端肉豆蔻酸与一个未知的高亲和力受体结合，该受体在一个未知的区室中促进摄取。
