Jolly Clare, Kashefi Kirk, Hollinshead Michael, Sattentau Quentin J
The Sir William Dunn School of Pathology, University of Oxford, UK.
J Exp Med. 2004 Jan 19;199(2):283-93. doi: 10.1084/jem.20030648.
Direct cell-cell transfer is an efficient mechanism of viral dissemination within an infected host, and human immunodeficiency virus 1 (HIV-1) can exploit this mode of spread. Receptor recognition by HIV-1 occurs via interactions between the viral surface envelope glycoprotein (Env), gp120, and CD4 and a chemokine receptor, CCR5 or CXCR4. Here, we demonstrate that the binding of CXCR4-using HIV-1-infected effector T cells to primary CD4(+)/CXCR4(+) target T cells results in rapid recruitment to the interface of CD4, CXCR4, talin, and lymphocyte function-associated antigen 1 on the target cell, and of Env and Gag on the effector cell. Recruitment of these membrane molecules into polarized clusters was dependent on Env engagement of CD4 and CXCR4 and required remodelling of the actin cytoskeleton. Transfer of Gag from effector to target cell was observed by 1 h after conjugate formation, was independent of cell-cell fusion, and was probably mediated by directed virion fusion with the target cell. We propose that receptor engagement by Env directs the rapid, actin-dependent recruitment of HIV receptors and adhesion molecules to the interface, resulting in a stable adhesive junction across which HIV infects the target cell.
直接的细胞间转移是病毒在受感染宿主体内传播的一种有效机制，人类免疫缺陷病毒1（HIV-1）可以利用这种传播方式。HIV-1通过病毒表面包膜糖蛋白（Env）gp120与CD4以及趋化因子受体CCR5或CXCR4之间的相互作用来识别受体。在此，我们证明，使用CXCR4的HIV-1感染的效应T细胞与原代CD4(+)/CXCR4(+)靶T细胞的结合导致CD4、CXCR4、踝蛋白和淋巴细胞功能相关抗原1迅速募集到靶细胞的界面，以及Env和Gag募集到效应细胞的界面。这些膜分子募集到极化簇中依赖于Env与CD4和CXCR4的结合，并且需要肌动蛋白细胞骨架的重塑。在形成共轭体1小时后观察到Gag从效应细胞转移到靶细胞，这一过程独立于细胞间融合，并且可能是由定向病毒体与靶细胞融合介导的。我们提出，Env与受体的结合引导HIV受体和黏附分子迅速、依赖肌动蛋白地募集到界面，从而形成一个稳定的黏附连接，HIV通过该连接感染靶细胞。
