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Assembly of infectious HIV-1 in human epithelial and T-lymphoblastic cell lines.
- Source :
-
Journal of molecular biology [J Mol Biol] 2006 Jun 16; Vol. 359 (4), pp. 848-62. Date of Electronic Publication: 2006 Apr 25. - Publication Year :
- 2006
-
Abstract
- The canonical view of the ultimate steps of HIV-1 replication is that virus assembly and budding are taking place at the plasma membrane of infected cells. Surprisingly, recent studies revealed that these steps also occur on endosomal membranes in the interior of infected cells, such as macrophages. This prompted us to revisit the site of HIV-1 assembly in human epithelial-like cells and in infected human T-lymphoblastic cells. To address this question, we investigated the intracellular location of the major viral structural components of HIV-1, namely Gag, Env and the genomic RNA. Using a sub-cellular fractionation method, as well as immuno-confocal and electron microscopy, we show that Gag, the Env glycoproteins and the genomic RNA accumulate in late endosomes that contain infectious HIV-1 particles. In epithelial-like 293T cells, HIV-1 assembles and buds both at the plasma membrane and in endosomes, while in chronically infected human T lymphocytes, viral assembly mostly occurs within the cell where large amounts of infectious virions accumulate in endosomal compartments. In addition, HIV-1 release could be enhanced by ionomycin, a drug stimulating calcium-dependent exocytosis. These results favour the view that newly made Gag molecules associate with the genomic RNA in the cytosol, then viral core complexes can be targeted to late endosomes together with Env, where infectious HIV-1 are made and subsequently released by exocytosis.
- Subjects :
- Calcium metabolism
Cell Fractionation
Cell Line
Cell Membrane metabolism
Cell Membrane virology
Endosomes metabolism
Endosomes virology
Epithelial Cells drug effects
Epithelial Cells metabolism
Exocytosis physiology
Gene Products, env metabolism
Gene Products, gag metabolism
HIV-1 drug effects
Humans
Ionomycin pharmacology
Microscopy, Confocal methods
Microscopy, Electron methods
RNA, Viral metabolism
T-Lymphocytes drug effects
T-Lymphocytes metabolism
Virion pathogenicity
Epithelial Cells virology
HIV-1 pathogenicity
HIV-1 physiology
T-Lymphocytes virology
Virus Assembly
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2836
- Volume :
- 359
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 16682056
- Full Text :
- https://doi.org/10.1016/j.jmb.2006.04.017