A role for ubiquitin ligase recruitment in retrovirus release
Open accessAbstract
Retroviral Gag polyproteins have specific regions, commonly referred to as late assembly (L) domains, which are required for the efficient separation of assembled virions from the host cell. The L domain of HIV-1 is in the C-terminal p6 gag domain and contains an essential P(T/S)AP core motif that is widely conserved among lentiviruses. In contrast, the L domains of oncoretroviruses such as Rous sarcoma virus (RSV) have a more N-terminal location and a PPxY core motif. In the present study, we used chimeric Gag constructs to probe for L domain activity, and observed that the unrelated L domains of RSV and HIV-1 both induced the appearance of Gag-ubiquitin conjugates in virus-like particles (VLP). Furthermore, a single-amino acid substitution that abolished the activity of the RSV L domain in VLP release also abrogated its ability to induce Gag ubiquitination. Particularly robust Gag ubiquitination and enhancement of VLP release were observed in the presence of the candidate L domain of Ebola virus, which contains overlapping P(T/S)AP and PPxY motifs. The release defect of a minimal Gag construct could also be corrected through the attachment of a peptide that serves as a physiological docking site for the ubiquitin ligase Nedd4. Furthermore, VLP formation by a full-length Gag polyprotein was sensitive to lactacystin, which depletes the levels of free ubiquitin through inhibition of the proteasome. Our findings suggest that the engagement of the ubiquitin conjugation machinery by L domains plays a crucial role in the release of a diverse group of enveloped viruses.
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?
Ubiquitination of Gag is a common feature among retroviruses, intricately associated with retroviral budding/release.
“ubiquitination of Gag is a common feature among retroviruses, intricately associated with retroviral budding/release”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Strack et al. 2000
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
Flagged first, then by citations
Cited by
Sorted by citations
Martin-Serrano, J., Zang, T., & Bieniasz, P. D. (2001) · Nature Medicine · doi:10.1038/nm1201-1313 · Cited by 710 · see citing works
VerPlank, L., Bouamr, F., LaGrassa, T. J., Agresta, B., Kikonyogo, A., Leis, J., & Carter, C. A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.131059198 · Cited by 584 · see citing works
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
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
Demirov, D. G., Orenstein, J. M., & Freed, E. O. (2002) · Journal of Virology · doi:10.1128/jvi.76.1.105-117.2002 · Cited by 201 · see citing works
Vesicular Release of Ebola Virus Matrix Protein VP40
Timmins, J., Scianimanico, S., Schoehn, G., & Weissenhorn, W. (2001) · Virology · doi:10.1006/viro.2001.0860 · Cited by 190 · see citing works
Ebola Virus Matrix Protein VP40 Uses the COPII Transport System for Its Intracellular Transport
Yamayoshi, S., Noda, T., Ebihara, H., Goto, H., Morikawa, Y., Lukashevich, I. S., Neumann, G., Feldmann, H., & Kawaoka, Y. (2008) · Cell Host & Microbe · doi:10.1016/j.chom.2008.02.001 · Cited by 100 · 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
Strack, B., Calistri, A., & Göttlinger, H. G. (2002) · Journal of Virology · doi:10.1128/jvi.76.11.5472-5479.2002 · Cited by 80 · see citing works
Self-citationBeyond 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 (Wills et al. 1994 , Parent et al. 1995 , Puffer et al. 1997 , Patnaik et al. 2000 , Schubert et al. 2000 , Strack et al. 2000 , Vogt 2000 , Le Blanc et al. 2002 , Myers and Allen 2002 , Gottwein et al. 2003 , Patton et al. 2005 , Narahara and Yasuda 2015 , Bartusch and Prange 2016 , Del…”
- Authors
- Strack, B., Calistri, A., Accola, M. A., Palù, G., & Göttlinger, H. G.
- Affiliations
- Harvard University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2000-11-21
- Volume
- 97
- Issue
- 24
- Pages
- 13063-13068
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC27178
- OpenAlex
- W2115909676
- Cited by
- 309
- References
- 3
- Citations by year
- 2025: 6 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 9 · 2019: 5 · 2018: 6 · 2017: 6 · 2016: 6 · 2015: 6 · 2014: 8 · 2013: 9 · 2012: 6
- FWCI
- 11.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- National Institutes of Health (AI29873)
- Center for AIDS Research, University of Washington
- National Cancer Institute (T32 CA09141, T32CA009141)
- National Institute of Allergy and Infectious Diseases (AI29873, AI28691, P30AI028691, R37AI029873, R01AI029873)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Keywords
- Gag protein, ubiquitination, virus release, HIV-1, Rous sarcoma virus, Ebola virus, PPxY motif, virus-like particles, proteasome, lactacystin, lentivirus
- MeSH terms
- Amino Acid Sequence, Avian Sarcoma Viruses, HeLa Cells, Humans, Ligases, Molecular Sequence Data, Recombinant Proteins, Transfection, Ubiquitins, Virion, Virus Replication, HIV-1, Gene Products, gag, Sequence Alignment, Conserved Sequence, Sequence Homology, Amino Acid, Ebolavirus, Ubiquitin-Protein Ligases
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
