Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding
Open accessAbstract
Like other enveloped viruses, HIV-1 uses cellular machinery to bud from infected cells. We now show that Tsg101 protein, which functions in vacuolar protein sorting (Vps), is required for HIV-1 budding. The UEV domain of Tsg101 binds to an essential tetrapeptide (PTAP) motif within the p6 domain of the structural Gag protein and also to ubiquitin. Depletion of cellular Tsg101 by small interfering RNA arrests HIV-1 budding at a late stage, and budding is rescued by reintroduction of Tsg101. Dominant negative mutant Vps4 proteins that inhibit vacuolar protein sorting also arrest HIV-1 and MLV budding. These observations suggest that retroviruses bud by appropriating cellular machinery normally used in the Vps pathway to form multivesicular bodies.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
HIV-1 exploits host proteins such as TSG101 and ALIX to enhance its budding/release.
“HIV-1 exploits host proteins such as tumor susceptibility gene 101 (TSG101) and ALG-2 interacting protein X (ALIX) to enhance its budding/release.”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Garrus et al. 2001
The PT/SAP motif recruits ESCRT-I subunit TSG101, while the YPXnL motif in p6 mediates interaction with ALIX, a component of ESCRT-III complex.
“the PT/SAP motif recruits ESCRT-I subunit TSG101, while Tyr-Pro-Xn-Leu (YPXnL, where X is any residue and n is 1–3 amino acids) motif in the p6 mediates the interaction with ALIX, a component of ESCRT-III complex”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Garrus et al. 2001
Cites
Ubiquitin is part of the retrovirus budding machinery
Patnaik, A., Chau, V., & Wills, J. W. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.24.13069 · Cited by 292 · see citing works
Parent, L. J., Bennett, R. P., Craven, R. C., Nelle, T. D., Krishna, N. K., Bowzard, J. B., Wilson, C. B., Puffer, B. A., Montelaro, R. C., & Wills, J. W. (1995) · Journal of Virology · doi:10.1128/jvi.69.9.5455-5460.1995 · Cited by 258 · see citing works
Puffer, B. A., Parent, L. J., Wills, J. W., & Montelaro, R. C. (1997) · Journal of Virology · doi:10.1128/jvi.71.9.6541-6546.1997 · Cited by 217 · see citing works
Bishop, N., & Woodman, P. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009863200 · Cited by 187 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Biogenesis and secretion of exosomes
Kowal, J., Tkach, M., & Théry, C. (2014) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2014.05.004 · Cited by 1,781 · see citing works
Vietri, M., Radulovic, M., & Stenmark, H. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0177-4 · Cited by 962 · see citing works
AIP1/ALIX Is a Binding Partner for HIV-1 p6 and EIAV p9 Functioning in Virus Budding
Strack, B., Calistri, A., Craig, S., Popova, E., & Göttlinger, H. G. (2003) · Cell · doi:10.1016/s0092-8674(03)00653-6 · Cited by 825 · see citing works
Exosomes maintain cellular homeostasis by excreting harmful DNA from cells
Takahashi, A., Okada, R., Nagao, K., Kawamata, Y., Hanyu, A., Yoshimoto, S., Takasugi, M., Watanabe, S., Kanemaki, M. T., Obuse, C., et al. (2017) · Nature Communications · doi:10.1038/ncomms15287 · Cited by 761 · see citing works
HIV and Tuberculosis: a Deadly Human Syndemic
Kwan, C. K., & Ernst, J. D. (2011) · Clinical Microbiology Reviews · doi:10.1128/cmr.00042-10 · Cited by 720 · see citing works
Martin-Serrano, J., Zang, T., & Bieniasz, P. D. (2001) · Nature Medicine · doi:10.1038/nm1201-1313 · Cited by 710 · see citing works
Extracellular Vesicles and Nanoparticles: Emerging Complexities
Jeppesen, D. K., Zhang, Q., Franklin, J. L., & Coffey, R. J. (2023) · Trends in Cell Biology · doi:10.1016/j.tcb.2023.01.002 · Cited by 705 · see citing works
Chertova, E., Chertov, O., Coren, L. V., Roser, J. D., Trubey, C. M., Bess, J. W., Sowder, R. C., Barsov, E., Hood, B. L., Fisher, R. J., et al. (2006) · Journal of Virology · doi:10.1128/jvi.01013-06 · Cited by 462 · see citing works
Galectin-3 Coordinates a Cellular System for Lysosomal Repair and Removal
Jia, J., Claude-Taupin, A., Gu, Y., Choi, S. W., Peters, R., Bissa, B., Mudd, M. H., Allers, L., Pallikkuth, S., Lidke, K. A., et al. (2020) · Developmental Cell · doi:10.1016/j.devcel.2019.10.025 · Cited by 434 · see citing works
The Molecular Mechanism of Hepcidin-mediated Ferroportin Down-Regulation
De Domenico, I., Ward, D. M., Langelier, C., Vaughn, M. B., Nemeth, E., Sundquist, W. I., Ganz, T., Musci, G., & Kaplan, J. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-01-0060 · Cited by 434 · see citing works
Self-citationALIX- and ESCRT-III–dependent sorting of tetraspanins to exosomes
Larios, J., Mercier, V., Roux, A., & Gruenberg, J. (2020) · Journal of Cell Biology · doi:10.1083/jcb.201904113 · Cited by 422 · see citing works
Cellular Proteins in Influenza Virus Particles
Shaw, M. L., Stone, K. L., Colangelo, C. M., Gulcicek, E. E., & Palese, P. (2008) · PLoS Pathogens · doi:10.1371/journal.ppat.1000085 · Cited by 324 · see citing works
Modulation of Glucocorticoid Receptor Function via Phosphorylation
ISMAILI, N., & GARABEDIAN, M. J. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1321.007 · Cited by 318 · see citing works
Structural and Biochemical Studies of ALIX/AIP1 and Its Role in Retrovirus Budding
Fisher, R. D., Chung, H.-Y., Zhai, Q., Robinson, H., Sundquist, W. I., & Hill, C. P. (2007) · Cell · doi:10.1016/j.cell.2007.01.035 · Cited by 315 · see citing works
Self-citationLlano, M., Vanegas, M., Fregoso, O., Saenz, D., Chung, S., Peretz, M., & Poeschla, E. M. (2004) · Journal of Virology · doi:10.1128/jvi.78.17.9524-9537.2004 · Cited by 305 · see citing works
Current Knowledge on Exosome Biogenesis, Cargo-Sorting Mechanism and Therapeutic Implications
Xie, S., Zhang, Q., & Jiang, L. (2022) · Membranes · doi:10.3390/membranes12050498 · Cited by 262 · see citing works
Role of ESCRT-I in Retroviral Budding
Martin-Serrano, J., Zang, T., & Bieniasz, P. D. (2003) · Journal of Virology · doi:10.1128/jvi.77.8.4794-4804.2003 · Cited by 250 · see citing works
Host factors exploited by retroviruses
Goff, S. P. (2007) · Nature Reviews Microbiology · doi:10.1038/nrmicro1541 · Cited by 247 · see citing works
Retroviral spread by induction of virological synapses
Jolly, C., & Sattentau, Q. J. (2004) · Traffic · doi:10.1111/j.1600-0854.2004.00209.x · Cited by 240 · see citing works
Martinez, L. A., Naguibneva, I., Lehrmann, H., Vervisch, A., Tchénio, T., Lozano, G., & Harel-Bellan, A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.222406899 · Cited by 210 · see citing works
Raposo, G., & Marks, M. S. (2002) · Traffic · doi:10.1034/j.1600-0854.2002.030401.x · Cited by 161 · see citing works
Structural basis for activation, assembly and membrane binding of ESCRT-III Snf7 filaments
Tang, S., Henne, W. M., Borbat, P. P., Buchkovich, N. J., Freed, J. H., Mao, Y., Fromme, J. C., & Emr, S. D. (2015) · eLife · doi:10.7554/elife.12548 · Cited by 156 · see citing works
Tavassoli, A., Lu, Q., Gam, J., Pan, H., Benkovic, S. J., & Cohen, S. N. (2008) · ACS Chemical Biology · doi:10.1021/cb800193n · Cited by 153 · see citing works
Usami, Y., Popov, S., & Göttlinger, H. G. (2007) · Journal of Virology · doi:10.1128/jvi.00314-07 · Cited by 143 · see citing works
Kadiu, I., & Gendelman, H. E. (2011) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-011-9298-z · Cited by 100 · see citing works
The ESCRT machinery: new roles at new holes
Olmos, Y., & Carlton, J. (2016) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2015.12.001 · Cited by 98 · see citing works
Ubiquitin conjugation to Gag is essential for ESCRT-mediated HIV-1 budding
Sette, P., Nagashima, K., Piper, R. C., & Bouamr, F. (2013) · Retrovirology · doi:10.1186/1742-4690-10-79 · Cited by 81 · see citing works
Tartour, K., Nguyen, X.-N., Appourchaux, R., Assil, S., Barateau, V., Bloyet, L.-M., Burlaud Gaillard, J., Confort, M.-P., Escudero-Perez, B., Gruffat, H., et al. (2017) · PLOS Pathogens · doi:10.1371/journal.ppat.1006610 · Cited by 69 · see citing works
Basic Residues in the Nucleocapsid Domain of Gag Are Critical for Late Events of HIV-1 Budding
Dussupt, V., Sette, P., Bello, N. F., Javid, M. P., Nagashima, K., & Bouamr, F. (2011) · Journal of Virology · doi:10.1128/jvi.01562-10 · Cited by 60 · see citing works
Importance of viral late domains in budding and release of enveloped RNA viruses
Welker, L., Paillart, J.-C., & Bernacchi, S. (2021) · Viruses · doi:10.3390/v13081559 · Cited by 36 · see citing works
Recent advances in HIV-1 Gag inhibitor design and development
Dick, A., & Cocklin, S. (2020) · Molecules · doi:10.3390/molecules25071687 · Cited by 28 · see citing works
A Structural View on ESCRT-Mediated Abscission
Horváth, P., & Müller-Reichert, T. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.586880 · Cited by 16 · see citing works
Membrane manipulations by the ESCRT machinery
Odorizzi, G. (2015) · F1000Research · doi:10.12688/f1000research.6319.1 · Cited by 11 · see citing works
Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication
Jehad, M. A., Ali, L. M., Pillai, V. N., Prabhu, S. G., Mustafa, F., & Rizvi, T. A. (2026) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuaf066 · Cited by 5 · see citing works
“11 ) (Garrus et al. 2001 , Martin-Serrano et al. 2001 , VerPlank et al. 2001 , Demirov et al. 2002 , Strack et al. 2003 , Fisher et al. 2007 , Lee et al. 2007 , Mun-shi et al. 2007 , Zhai et al. 2008 , Dussupt et al. 2009 , Friedrich et al. 2016 , Schemelev et al. 2024 ).”
- Authors
- Garrus, J. E., von Schwedler, U. K., Pornillos, O. W., Morham, S. G., Zavitz, K. H., Wang, H. E., Wettstein, D. A., Stray, K. M., Côté, M., Rich, R. L., Myszka, D. G., & Sundquist, W. I.
- Affiliations
- University of Utah (US)
- Myriad Genetics (US)
- Corresponding author
- Sundquist, Wesley I.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2001-10
- Volume
- 107
- Issue
- 1
- Pages
- 55-65
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2130448025
- Cited by
- 1,369
- References
- 4
- Citations by year
- 2026: 18 · 2025: 18 · 2024: 32 · 2023: 29 · 2022: 27 · 2021: 38 · 2020: 46 · 2019: 40 · 2018: 34 · 2017: 32 · 2016: 29 · 2015: 36 · 2014: 49 · 2013: 55 · 2012: 66
- FWCI
- 28.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (P32 GM07464)
- 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
- TSG101, vacuolar protein sorting, HIV-1 budding, retroviral budding, PTAP motif, ubiquitin, VPS4, multivesicular bodies, murine leukemia virus
- MeSH terms
- Tsg101 Protein, Adenosine Triphosphatases, Cell Line, DNA-Binding Proteins, Fungal Proteins, Humans, Protein Binding, Recombinant Fusion Proteins, RNA, Transcription Factors, Vacuoles, HIV-1, Gene Products, gag, Genes, Reporter, Surface Plasmon Resonance, Two-Hybrid System Techniques, Amino Acid Motifs, Protein Transport, Ubiquitin, Saccharomyces cerevisiae Proteins, Endosomal Sorting Complexes Required for Transport
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
