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推薦原始出處： Cell, Volume 137,1 May 2009 doi:10.1016/j.cell.2009.02.046 HIV Enters Cells via Endocytosis and Dynamin-Dependent Fusion with Endosomes Kosuke Miyauchi1,2,Yuri Kim1,2,Olga Latinovic1,Vladimir Morozov1andGregory B. Melikyan1,, 1 Institute of Human Virology and Department of Microbiology and Immunology, University of Maryland School of Medicine, 725 W. Lombard Street, Baltimore, MD 21201, USA 2 These authors contributed equally to this work Summary Enveloped viruses that rely on a low pH-dependent step for entry initiate infection by fusing with acidic endosomes, whereas the entry sites for pH-independent viruses, such as HIV-1, have not been defined. These viruses have long been assumed to fuse directly with the plasma membrane. Here we used population-based measurements of the viral content delivery into the cytosol and time-resolved imaging of single viruses to demonstrate that complete HIV-1 fusion occurred in endosomes. In contrast, viral fusion with the plasma membrane did not progress beyond the lipid mixing step. HIV-1 underwent receptor-mediated internalization long before endosomal fusion, thus minimizing the surface exposure of conserved viral epitopes during fusion and reducing the efficacy of inhibitors targeting these epitopes. We also show that, strikingly, endosomal fusion is sensitive to a dynamin inhibitor, dynasore. These findings imply that HIV-1 infects cells via endocytosis and envelope glycoprotein- and dynamin-dependent fusion with intracellular compartments. (責任編輯：Doctor001) |
