Department of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.
Department of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.
Cell Host Microbe. 2016 Jul 13;20(1):25-35. doi: 10.1016/j.chom.2016.05.013. Epub 2016 Jun 16.
Hepatitis B virus (HBV) replication is strictly limited to the liver. Virions attach to hepatocytes through interactions of the viral PreS envelope protein domain with heparan sulfate proteoglycans (HSPGs). However, HSPG is ubiquitously present on many cell types, suggesting that HBV employs mechanisms to avoid attachment at extrahepatic sites. We demonstrate that HBV particles are released from cells in an inactive form with PreS hidden in the interior. These HSPG-non-binding (N-type) particles develop receptor binding competence by translocating PreS across the envelope onto their surface. Conversion into HSPG-binding (B-type) particles occurs spontaneously and renders HBV infectious. Low-dose inoculation of mice with human liver xenografts demonstrates superiority of N-type particles in establishing infections, while mature B-type virions, generated via N-type conversion, are profoundly impaired, correlating with non-selective accumulation in extrahepatic tissues. This dynamic topology switch represents a maturation process utilized by HBV to most likely avoid non-productive docking outside the liver.
乙型肝炎病毒 (HBV) 的复制严格局限于肝脏。病毒粒子通过病毒前 S 包膜蛋白结构域与硫酸乙酰肝素蛋白聚糖 (HSPG) 的相互作用附着到肝细胞上。然而，HSPG 在许多细胞类型中广泛存在，这表明 HBV 采用了避免在肝外部位附着的机制。我们证明，HBV 粒子以 PreS 隐藏在内部的无活性形式从细胞中释放。这些不与 HSPG 结合的 (N 型) 粒子通过将 PreS 穿过包膜转移到其表面而获得受体结合能力。自发发生转化为与 HSPG 结合的 (B 型) 粒子，并使 HBV 具有感染性。用人类肝异种移植物对小鼠进行低剂量接种表明 N 型粒子在建立感染方面具有优越性，而通过 N 型转化生成的成熟 B 型病毒粒子则受到严重损害，与非选择性地在肝外组织中积累相关。这种动态拓扑开关代表了 HBV 利用的成熟过程，很可能避免在肝脏外进行非生产性对接。
