Human ESCRT-II Complex and Its Role in Human Immunodeficiency Virus Type 1 Release
Open accessAbstract
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.
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Loss of ALIX recruitment to viral budding sites or cytokinetic bridges impairs but does not terminate these events.
“the loss of ALIX recruitment to viral budding sites through HIV L domain deletion or to cytokinetic bridges via cellular depletion by RNA interference (RNAi) impairs but does not terminate these events.”
From Budding of a Retrovirus: Some Assemblies Required (2020) · cites this paper as [17]
Redundant and parallel ESCRT-III recruiting axes are mandated.
“This mandates the presence of redundant and parallel ESCRT-III recruiting axes perhaps fulfilled by the intermediary ESCRT-II complex [13,17,18] or additional ALIX homologs and orthologs [19,20,21].”
From Budding of a Retrovirus: Some Assemblies Required (2020) · cites this paper as [17]
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“This mandates the presence of redundant and parallel ESCRT-III recruiting axes perhaps fulfilled by the intermediary ESCRT-II complex [13,17,18] or additional ALIX homologs and orthologs [19–21].”
Background
- Authors
- Langelier, C., von Schwedler, U. K., Fisher, R. D., De Domenico, I., White, P. L., Hill, C. P., Kaplan, J., Ward, D., & Sundquist, W. I.
- Affiliations
- University of Utah (US)
- Departments of Biochemistry
- Pathology, University of Utah, Salt Lake City, Utah 84112
- Corresponding author
- Sundquist, Wesley I.
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2006-10
- Volume
- 80
- Issue
- 19
- Pages
- 9465-9480
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC1617254
- OpenAlex
- W2128892763
- Cited by
- 166
- References
- 6
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 5 · 2021: 7 · 2020: 8 · 2019: 4 · 2018: 10 · 2017: 8 · 2016: 5 · 2015: 5 · 2014: 10 · 2013: 10 · 2012: 16
- FWCI
- 6.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Virology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AI51174)
- National Heart, Lung, and Blood Institute (HL29622)
- National Institute of General Medical Sciences (GM 066521, P01GM066521)
- National Institute of Allergy and Infectious Diseases (AI-51174, R01AI051174, R37AI051174)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK070947, R01DK070947)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- HIV-1 budding, multivesicular bodies, TSG101, VPS4, ubiquitin binding, protein sorting, vesicle formation, viral release, HIV-1 infectivity
- MeSH terms
- ATPases Associated with Diverse Cellular Activities, Adenosine Triphosphatases, Animals, Carrier Proteins, Chlorocebus aethiops, DNA-Binding Proteins, Humans, Models, Molecular, Protein Binding, Repressor Proteins, Saccharomyces cerevisiae, Virion, Biosensing Techniques, Biomarkers, HIV-1, Down-Regulation, Protein Structure, Tertiary, COS Cells, Two-Hybrid System Techniques, Vacuolar Proton-Translocating ATPases, Ubiquitin, Vesicular Transport Proteins, Endosomal Sorting Complexes Required for Transport, ErbB Receptors
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