Jolly Clare, Sattentau Quentin J
The Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom.
J Virol. 2005 Sep;79(18):12088-94. doi: 10.1128/JVI.79.18.12088-12094.2005.
Human immunodeficiency virus type 1 (HIV-1) can spread directly between T cells by forming a supramolecular structure termed a virological synapse (VS). HIV-1 envelope glycoproteins (Env) are required for VS assembly, but their mode of recruitment is unclear. We investigated the distribution of GM1-rich lipid rafts in HIV-1-infected (effector) T cells and observed Env colocalization with polarized raft markers GM1 and CD59 but not with the transferrin receptor that is excluded from lipid rafts. In conjugates of effector T cells and target CD4+ T cells, GM1, Env, and Gag relocated to the cell-cell interface. The depletion of cholesterol in the infected cell dispersed Env and GM1 within the plasma membrane, eliminated Gag clustering at the site of cell-cell contact, and abolished assembly of the VS. Raft integrity is therefore critical for Env and Gag co-clustering and VS assembly in T-cell conjugates.
1型人类免疫缺陷病毒（HIV-1）可通过形成一种称为病毒突触（VS）的超分子结构在T细胞之间直接传播。VS组装需要HIV-1包膜糖蛋白（Env），但其招募方式尚不清楚。我们研究了富含GM1的脂筏在HIV-1感染的（效应）T细胞中的分布，观察到Env与极化的筏标记物GM1和CD59共定位，但与被排除在脂筏之外的转铁蛋白受体不共定位。在效应T细胞与靶CD4+T细胞的结合物中，GM1、Env和Gag重新定位到细胞-细胞界面。感染细胞中胆固醇的消耗使Env和GM1分散在质膜内，消除了细胞-细胞接触部位的Gag聚集，并废除了VS的组装。因此，筏的完整性对于T细胞结合物中Env和Gag的共聚集以及VS的组装至关重要。
