Human ESCRT-II complex and its role in human immunodeficiency virus type 1 release.
The budding of many enveloped RNA viruses, including human immunodeficiency virus type 1 (HIV-1), requires some of the same cellular machinery as vesicle formation at the multivesicular body (MVB). In Saccharomyces cerevisiae, the ESCRT-II complex performs a central role in MVB protein sorting and vesicle formation, as it is recruited ... by the upstream ESCRT-I complex and nucleates assembly of the downstream ESCRT-III complex. Here, we report that the three subunits of human ESCRT-II, EAP20, EAP30, and EAP45, have a number of properties in common with their yeast orthologs. Specifically, EAP45 bound ubiquitin via its N-terminal GRAM-like ubiquitin-binding in EAP45 (GLUE) domain, both EAP45 and EAP30 bound the C-terminal domain of TSG101/ESCRT-I, and EAP20 bound the N-terminal half of CHMP6/ESCRT-III. Consistent with its expected role in MVB vesicle formation, (i) human ESCRT-II localized to endosomal membranes in a VPS4-dependent fashion and (ii) depletion of EAP20/ESCRT-II and CHMP6/ESCRT-III inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor, albeit to a lesser extent than depletion of TSG101/ESCRT-I. Nevertheless, HIV-1 release and infectivity were not reduced by efficient small interfering RNA depletion of EAP20/ESCRT-II or CHMP6/ESCRT-III. These observations indicate that there are probably multiple pathways for protein sorting/MVB vesicle formation in human cells and that HIV-1 does not utilize an ESCRT-II-dependent pathway to leave the cell.
Mesh Terms:
Adenosine Triphosphatases, Animals, Biological Markers, Biosensing Techniques, COS Cells, Carrier Proteins, Cercopithecus aethiops, DNA-Binding Proteins, Down-Regulation, Endosomal Sorting Complexes Required for Transport, HIV-1, Humans, Models, Molecular, Protein Binding, Protein Structure, Tertiary, Receptor, Epidermal Growth Factor, Repressor Proteins, Saccharomyces cerevisiae, Two-Hybrid System Techniques, Ubiquitin, Vesicular Transport Proteins, Virion
Adenosine Triphosphatases, Animals, Biological Markers, Biosensing Techniques, COS Cells, Carrier Proteins, Cercopithecus aethiops, DNA-Binding Proteins, Down-Regulation, Endosomal Sorting Complexes Required for Transport, HIV-1, Humans, Models, Molecular, Protein Binding, Protein Structure, Tertiary, Receptor, Epidermal Growth Factor, Repressor Proteins, Saccharomyces cerevisiae, Two-Hybrid System Techniques, Ubiquitin, Vesicular Transport Proteins, Virion
J. Virol.
Date: Oct. 01, 2006
PubMed ID: 16973552
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