HIV Enters Cells via Endocytosis and Dynamin-Dependent Fusion with Endosomes
By Kosuke Miyauchi, Yuri Kim, O. Latinovic, V. Morozov, G. Melikyan. Cell, 2009
705 citations recorded by the source corpus.
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. These findings imply that HIV-1 infects cells via envelope glycoprotein- and dynamin-dependent fusion with intracellular compartments.
Subfields: Cell Biology, Public Health, Environmental and Occupational Health, Virology
View Paper: https://www.semanticscholar.org/paper/4f63832bed31eff3db3d683ec732e49de25657f5
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Citations in the corpus
- Subcellular targeting strategies for drug design and delivery (2010, background): “Although HIV fusion is presumed to occur at the plasma membrane, a new study using high-resolution time lapse imaging suggests that the fusion of HIV occurs in the endosome”
- Distinct Patterns of IFITM-Mediated Restriction of Filoviruses, SARS Coronavirus, and Influenza A Virus (2011, background): “In contrast, other entry proteins such as the envelope proteins of HIV-1 and MLV do not require access to an acidic compartment, and these viruses are presumed to fuse at the plasma membrane or in an early endocytic vesicle [9].”
- Phosphoinositides: tiny lipids with giant impact on cell regulation. (2013, background): “coli (1348), Salmonella (1544), or viruses such as hepatitis C (1577), HIV (1069), or influenza (472), just to name a few from an ever-increasing list.”
- HIV: cell binding and entry. (2012, background): “Homozygosity for this polymorphism results in profound resistance to HIV infection, although several D32 homozygotes have been infected with X4 viruses (Balotta et al. 1997; O’Brien et al. 1997; Theodorou et al. 1997).”