Large hepatitis delta antigen is a novel clathrin adaptor-like protein
Large hepatitis delta antigen is a novel clathrin adaptor-like protein
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DOI：
10.1128/jvi.02809-06
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发表时间：
2007-06-01
影响因子：
5.4
通讯作者：
Chang, Ming-Fu
中科院分区：
文献类型：
--
作者：
Huang, Cheng;Chang, Shin C.;Chang, Ming-Fu
笼状蛋白介导的内吞作用是病毒进入的一种常见途径，但对病毒蛋白与胞浆中的笼状蛋白的直接联系知之甚少。在这项研究中，在大型丁型肝炎抗原(HDAg-L)的C末端发现了一个已知保守的网状蛋白适配器。与网状蛋白接头类似，HDAG-L通过网状蛋白盒直接与网状蛋白重链的N端相互作用。HDAg-L是一种对丁型肝炎病毒装配起重要作用的核质穿梭蛋白。在这里，我们证明了灯盏花素A和Wortmannin分别是网状蛋白介导的胞吐作用和内体转运的抑制剂，它们特异性地阻断了HDV的组装，但对乙肝病毒小表面抗原的组装没有影响。此外，胞质定位的hDAg-L还能抑制转铁蛋白的胞吞作用和表皮生长因子受体的降解。这些结果表明，HDAg-L是一种新的网状蛋白适配子，可能通过与网状蛋白的相互作用参与HDV与乙肝病毒重叠感染的成熟和致病过程。
Clathrin-mediated endocytosis is a common pathway for viral entry, but little is known about the direct association of viral protein with clathrin in the cytoplasm. In this study, a putative clathrin box known to be conserved in clathrin adaptors was identified at the C terminus of the large hepatitis delta antigen (HDAg-L). Similar to clathrin adaptors, HDAg-L directly interacted with the N terminus of the clathrin heavy chain through the clathrin box. HDAg-L is a nucleocytoplasmic shuttle protein important for the assembly of hepatitis delta virus (HDV). Here, we demonstrated that brefeldin A and wortmannin, inhibitors of clathrin-mediated exocytosis and endosomal trafficking, respectively, specifically blocked HDV assembly but had no effect on the assembly of the small surface antigen of hepatitis B virus. In addition, cytoplasm-localized HDAg-L inhibited the clathrin-mediated endocytosis of transferrin and the degradation of epidermal growth factor receptor. These results indicate that HDAg-L is a new clathrin adaptor-like protein, and it may be involved in the maturation and pathogenesis of HDV coinfection or superinfection with hepatitis B virus through interaction with clathrin.