Cellular uptake of hepatitis B virus envelope L particles is independent of sodium taurocholate cotransporting polypeptide, but dependent on heparan sulfate proteoglycan
Cellular uptake of hepatitis B virus envelope L particles is independent of sodium taurocholate cotransporting polypeptide, but dependent on heparan sulfate proteoglycan
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DOI：
10.1016/j.virol.2016.06.024
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发表时间：
2016-10-01
期刊：
影响因子：
3.7
通讯作者：
Kuroda, Shun'ichi
中科院分区：
文献类型：
--
作者：
Somiya, Masaharu;Liu, Qiushi;Kuroda, Shun'ichi
牛磺酸胆酸钠共转运多肽（NTCP）最近被发现为乙型肝炎病毒（HBV）受体，但HBV进入的详细机制尚不完全清楚。我们利用重组HBV表面抗原L蛋白颗粒（生物纳米胶囊，bnc）研究了HBV进入细胞的途径。用肉豆蔻酰基修饰bnc中的L蛋白后，在体外发现肉豆蔻酰基化bnc （myr - bnc）与NTCP结合，并竞争性地抑制体外HBV感染，这表明myr - bnc与HBV共享NTCP依赖的感染机制。然而，myr - bnc和血浆源性HBV表面抗原（HBsAg）颗粒的细胞进入率与ntcp -过表达HepG2细胞中的bnc相同。此外，这些颗粒的细胞进入主要是由硫酸肝素蛋白多糖介导的内吞作用驱动的，而与NTCP的表达无关。综上所述，细胞表面NTCP可能不参与HBV的细胞摄取，而细胞内NTCP可能起关键作用。(C) 2016 Elsevier Inc.版权所有。
Sodium taurocholate cotransporting polypeptide (NTCP) was recently discovered as a hepatitis B virus (HBV) receptor, however, the detailed mechanism of HBV entry is not yet fully understood. We investigated the cellular entry pathway of HBV using recombinant HBV surface antigen L protein particles (bio-nanocapsules, BNCs). After the modification of L protein in BNCs with myristoyl group, myristoylated BNCs (Myr-BNCs) were found to bind to NTCP in vitro, and inhibit in vitro HBV infection competitively, suggesting that Myr-BNCs share NTCP-dependent infection machinery with HBV. Nevertheless, the cellular entry rates of Myr-BNCs and plasma-derived HBV surface antigen (HBsAg) particles were the same as those of BNCs in NTCP-overexpressing HepG2 cells. Moreover, the cellular entry of these particles was mainly driven by heparan sulfate proteoglycan-mediated endocytosis regardless of NTCP expression. Taken together, cell-surface NTCP may not be involved in the cellular uptake of HBV, while presumably intracellular NTCP plays a critical role. (C) 2016 Elsevier Inc. All rights reserved.