Mañes S, del Real G, Lacalle R A, Lucas P, Gómez-Moutón C, Sánchez-Palomino S, Delgado R, Alcamí J, Mira E, Martínez-A C
Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Madrid, Spain.
EMBO Rep. 2000 Aug;1(2):190-6. doi: 10.1093/embo-reports/kvd025.
HIV-1 infection triggers lateral membrane diffusion following interaction of the viral envelope with cell surface receptors. We show that these membrane changes are necessary for infection, as initial gp120-CD4 engagement leads to redistribution and clustering of membrane microdomains, enabling subsequent interaction of this complex with HIV-1 co-receptors. Disruption of cell membrane rafts by cholesterol depletion before viral exposure inhibits entry by both X4 and R5 strains of HIV-1, although viral replication in infected cells is unaffected by this treatment. This inhibitory effect is fully reversed by cholesterol replenishment of the cell membrane. These results indicate a general mechanism for HIV-1 envelope glycoprotein-mediated fusion by reorganization of membrane microdomains in the target cell, and offer new strategies for preventing HIV-1 infection.
HIV-1感染在病毒包膜与细胞表面受体相互作用后引发细胞膜侧向扩散。我们发现这些膜变化对于感染是必要的，因为最初的gp120-CD4结合会导致膜微结构域的重新分布和聚集，从而使该复合物随后能够与HIV-1共受体相互作用。在病毒暴露前通过胆固醇耗竭破坏细胞膜脂筏会抑制HIV-1的X4和R5毒株的进入，尽管这种处理对感染细胞中的病毒复制没有影响。通过补充细胞膜胆固醇可完全逆转这种抑制作用。这些结果表明了一种由HIV-1包膜糖蛋白介导的、通过靶细胞膜微结构域重组实现融合的普遍机制，并为预防HIV-1感染提供了新策略。
