Gallo Stephen A, Finnegan Catherine M, Viard Mathias, Raviv Yossef, Dimitrov Antony, Rawat Satinder S, Puri Anu, Durell Stewart, Blumenthal Robert
Laboratory of Experimental and Computational Biology, Center for Cancer Research, NCI-Frederick, National Institute of Health, Miller Drive, Frederick, MD 21702-1201, USA.
Biochim Biophys Acta. 2003 Jul 11;1614(1):36-50. doi: 10.1016/s0005-2736(03)00161-5.
The current general model of HIV viral entry involves the binding of the trimeric viral envelope glycoprotein gp120/gp41 to cell surface receptor CD4 and chemokine co-receptor CXCR4 or CCR5, which triggers conformational changes in the envelope proteins. Gp120 then dissociates from gp41, allowing for the fusion peptide to be inserted into the target membrane and the pre-hairpin configuration of the ectodomain to form. The C-terminal heptad repeat region and the leucine/isoleucine zipper region then form the thermostable six-helix coiled-coil, which drives the membrane merger and eventual fusion. This model needs updating, as there has been a wealth of data produced in the last few years concerning HIV entry, including target cell dependencies, fusion kinetic data, and conformational intermediates. A more complete model must include the involvement of membrane microdomains, actin polymerization, glycosphingolipids, and possibly CD4 and chemokine signaling in entry. In addition, kinetic experiments involving the addition of fusion inhibitors have revealed some of the rate-limiting steps in this process, adding a temporal component to the model. A review of these data that may require an updated version of the original model is presented here.
目前，HIV病毒进入细胞的一般模型涉及三聚体病毒包膜糖蛋白gp120/gp41与细胞表面受体CD4以及趋化因子共受体CXCR4或CCR5的结合，这会触发包膜蛋白的构象变化。然后，gp120与gp41解离，使融合肽插入靶膜并形成胞外域的前发夹结构。C端七肽重复区域和亮氨酸/异亮氨酸拉链区域随后形成热稳定的六螺旋卷曲螺旋，驱动膜融合并最终实现融合。由于在过去几年中产生了大量关于HIV进入细胞的数据，包括靶细胞依赖性、融合动力学数据和构象中间体，因此该模型需要更新。一个更完整的模型必须包括膜微结构域、肌动蛋白聚合、糖鞘脂的参与，以及进入过程中可能涉及的CD4和趋化因子信号传导。此外，涉及添加融合抑制剂的动力学实验揭示了这一过程中的一些限速步骤，为该模型增加了时间因素。本文对这些可能需要更新原始模型的数据进行了综述。
