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PMID:19410541
| Citation |
Miyauchi, K, Kim, Y, Latinovic, O, Morozov, V and Melikyan, GB (2009) HIV enters cells via endocytosis and dynamin-dependent fusion with endosomes. Cell 137:433-44 |
|---|---|
| Abstract |
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. |
| Links |
PubMed PMC2696170 Online version:10.1016/j.cell.2009.02.046 |
| Keywords |
Cell Membrane/metabolism; Cell Membrane/virology; Cells, Cultured; Clathrin/metabolism; Cytosol/metabolism; Cytosol/ultrastructure; Cytosol/virology; Dynamins/antagonists & inhibitors; Dynamins/metabolism; Endocytosis; HIV Envelope Protein gp41/chemistry; HIV Envelope Protein gp41/metabolism; HIV Infections/metabolism; HIV Infections/virology; HIV-1/chemistry; HIV-1/physiology; HIV-1/ultrastructure; Humans; Hydrazones/metabolism; Membrane Lipids/metabolism; Microscopy, Confocal; Protein Conformation; Protein Transport; Virus Internalization |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
involved_in |
GO:0075512: clathrin-dependent endocytosis of virus by host cell |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
Notes
See also
References
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