Vif hijacks CBF-β to degrade APOBEC3G and promote HIV-1 infection
Open accessAbstract
Restriction factors, such as the retroviral complementary DNA deaminase APOBEC3G, are cellular proteins that dominantly block virus replication. The AIDS virus, human immunodeficiency virus type 1 (HIV-1), produces the accessory factor Vif, which counteracts the host's antiviral defence by hijacking a ubiquitin ligase complex, containing CUL5, ELOC, ELOB and a RING-box protein, and targeting APOBEC3G for degradation. Here we reveal, using an affinity tag/purification mass spectrometry approach, that Vif additionally recruits the transcription cofactor CBF-β to this ubiquitin ligase complex. CBF-β, which normally functions in concert with RUNX DNA binding proteins, allows the reconstitution of a recombinant six-protein assembly that elicits specific polyubiquitination activity with APOBEC3G, but not the related deaminase APOBEC3A. Using RNA knockdown and genetic complementation studies, we also demonstrate that CBF-β is required for Vif-mediated degradation of APOBEC3G and therefore for preserving HIV-1 infectivity. Finally, simian immunodeficiency virus (SIV) Vif also binds to and requires CBF-β to degrade rhesus macaque APOBEC3G, indicating functional conservation. Methods of disrupting the CBF-β-Vif interaction might enable HIV-1 restriction and provide a supplement to current antiviral therapies that primarily target viral proteins.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The Vif protein of HIV hijacks CRL5 and binds CBF-b, leading to degradation of A3F and A3G.
“For instance, the Vif protein of the human immunodeficiency virus (HIV) hijacks CRL5 and binds the cotranscription factor CBF-b leading to degradation of A3F and A3G, proteins that block viral replication.[95][96][97]”
From Chasing molecular glue degraders: screening approaches (2022) · cites this paper as [97]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein
Sheehy, A. M., Gaddis, N., Choi, J. D., & Malim, M. H. (2002) · Nature · doi:10.1038/nature00939 · Cited by 2,330 · see citing works
Recognition of the polyubiquitin proteolytic signal
Thrower, J. S., Hoffman, L. M., Rechsteiner, M., & Pickart, C. M. (2000) · The EMBO Journal · doi:10.1093/emboj/19.1.94 · Cited by 1,718 · see citing works
Induction of APOBEC3G Ubiquitination and Degradation by an HIV-1 Vif-Cul5-SCF Complex
Yu, X., Yu, Y., Liu, B., Luo, K., Kong, W., Mao, P., & Yu, X.-F. (2003) · Science · doi:10.1126/science.1089591 · Cited by 1,194 · see citing works
The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif
Sheehy, A. M., Gaddis, N., & Malim, M. H. (2003) · Nature Medicine · doi:10.1038/nm945 · Cited by 961 · see citing works
Global landscape of HIV–human protein complexes
Jäger, S., Cimermancic, P., Gulbahce, N., Johnson, J. R., McGovern, K. E., Clarke, S. C., Shales, M., Mercenne, G., Pache, L., Li, K., et al. (2012) · Nature · doi:10.1038/nature10719 · Cited by 731 · see citing works
Self-citationStopak, K., de Noronha, C. M. C., Yonemoto, W. M., & Greene, W. C. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00353-8 · Cited by 723 · see citing works
HIV-1 Accessory Proteins—Ensuring Viral Survival in a Hostile Environment
Malim, M. H., & Emerman, M. (2008) · Cell Host & Microbe · doi:10.1016/j.chom.2008.04.008 · Cited by 549 · see citing works
Kamura, T., Maenaka, K., Kotoshiba, S., Matsumoto, M., Kohda, D., Conaway, R. C., Conaway, J. W., & Nakayama, K. I. (2004) · Genes & Development · doi:10.1101/gad.1252404 · Cited by 476 · see citing works
Mehle, A., Strack, B., Ancuța, P., Zhang, C., McPike, M. P., & Gabuzda, D. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313093200 · Cited by 470 · see citing works
The Vif Protein of HIV Triggers Degradation of the Human Antiretroviral DNA Deaminase APOBEC3G
Conticello, S. G., Harris, R. S., & Neuberger, M. S. (2003) · Current Biology · doi:10.1016/j.cub.2003.10.034 · Cited by 468 · see citing works
Self-citationKim, H. T., Kim, K. P., Lledı́as, F., Kisselev, A. F., Scaglione, K. M., Skowyra, D., Gygi, S. P., & Goldberg, A. L. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m609659200 · Cited by 438 · see citing works
Multimodal Activation of the Ubiquitin Ligase SCF by Nedd8 Conjugation
Saha, A., & Deshaies, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.08.021 · Cited by 396 · see citing works
Refsland, E. W., Stenglein, M. D., Shindo, K., Albin, J. S., Brown, W. L., & Harris, R. S. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq174 · Cited by 356 · see citing works
Self-citationHultquist, J. F., Lengyel, J., Refsland, E. W., LaRue, R. S., Lackey, L., Brown, W. L., & Harris, R. S. (2011) · Journal of Virology · doi:10.1128/jvi.05238-11 · Cited by 339 · see citing works
Self-citationDefining APOBEC3 Expression Patterns in Human Tissues and Hematopoietic Cell Subsets
Koning, F. A., Newman, E. N. C., Kim, E., Kunstman, K., Wolinsky, S. M., & Malim, M. H. (2009) · Journal of Virology · doi:10.1128/jvi.01089-09 · Cited by 334 · see citing works
APOBEC3 proteins mediate the clearance of foreign DNA from human cells
Stenglein, M. D., Burns, M. B., Li, M., Lengyel, J., & Harris, R. S. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1744 · Cited by 326 · see citing works
Self-citationGetting into position: the catalytic mechanisms of protein ubiquitylation
Passmore, L. A., & Barford, D. (2004) · Biochemical Journal · doi:10.1042/bj20040198 · Cited by 305 · see citing works
Petroski, M. D., & Deshaies, R. J. (2005) · Cell · doi:10.1016/j.cell.2005.09.033 · Cited by 304 · see citing works
Mehle, A., Gonçalves, J., Santa‐Marta, M., McPike, M. P., & Gabuzda, D. H. (2004) · Genes & Development · doi:10.1101/gad.1249904 · Cited by 294 · see citing works
E2-RING Expansion of the NEDD8 Cascade Confers Specificity to Cullin Modification
Huang, D. T. C., Ayrault, O., Hunt, H. W., Taherbhoy, A. M., Duda, D. M., Scott, D. C., Borg, L. A., Neale, G. A. M., Murray, P. J., Roussel, M. F., et al. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.01.011 · Cited by 282 · see citing works
Sequential E2s Drive Polyubiquitin Chain Assembly on APC Targets
Rodrigo-Brenni, M. C., & Morgan, D. O. (2007) · Cell · doi:10.1016/j.cell.2007.05.027 · Cited by 250 · see citing works
Retrovirus Restriction Factors
Goff, S. P. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.12.001 · Cited by 215 · see citing works
Interactions of host APOBEC3 restriction factors with HIV-1 in vivo: implications for therapeutics
Albin, J. S., & Harris, R. S. (2010) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399409001343 · Cited by 185 · see citing works
Self-citationStanley, B. J., Ehrlich, E. S., Short, L., Yu, Y., Xiao, Z., Yu, X.-F., & Xiong, Y. (2008) · Journal of Virology · doi:10.1128/jvi.00767-08 · Cited by 131 · see citing works
Priming and Extending: A UbcH5/Cdc34 E2 Handoff Mechanism for Polyubiquitination on a SCF Substrate
Wu, K., Kovacev, J., & Pan, Z.-Q. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.02.025 · Cited by 126 · see citing works
Interplay of transcription factors in T-cell differentiation and function: the role of Runx
Wong, W. F., Kohu, K., Chiba, T., Sato, T., & Satake, M. (2010) · Immunology · doi:10.1111/j.1365-2567.2010.03381.x · Cited by 112 · see citing works
DeHart, J. L., Bosque, A., Harris, R. S., & Planelles, V. (2008) · Journal of Virology · doi:10.1128/jvi.00377-08 · Cited by 58 · see citing works
Self-citationPurification and characterization of HIV–human protein complexes
Jäger, S., Gulbahce, N., Cimermančič, P., Kane, J., He, N., Chou, S., D’Orso, I., Fernandes, J. D., Jang, G. Μ., Frankel, A. D., et al. (2010) · Methods · doi:10.1016/j.ymeth.2010.08.007 · Cited by 57 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Global landscape of HIV–human protein complexes
Jäger, S., Cimermancic, P., Gulbahce, N., Johnson, J. R., McGovern, K. E., Clarke, S. C., Shales, M., Mercenne, G., Pache, L., Li, K., et al. (2012) · Nature · doi:10.1038/nature10719 · Cited by 731 · see citing works
Self-citationBulatov, E., & Ciulli, A. (2015) · Biochemical Journal · doi:10.1042/bj20141450 · Cited by 237 · see citing works
Structural basis for hijacking CBF-β and CUL5 E3 ligase complex by HIV-1 Vif
Guo, Y., Dong, L., Qiu, X., Wang, Y., Zhang, B., Liu, H., Yu, Y., Zang, Y., Yang, M., & Huang, Z. (2014) · Nature · doi:10.1038/nature12884 · Cited by 202 · see citing works
Chasing molecular glue degraders: screening approaches
Domostegui, A., Nieto-Barrado, L., Perez-Lopez, C., & Mayor-Ruiz, C. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00197g · Cited by 200 · see citing works
Miteva, Y. V., Budayeva, H. G., & Cristea, I. M. (2013) · Analytical Chemistry · doi:10.1021/ac3033257 · Cited by 105 · see citing works
Cullin E3 Ligases and Their Rewiring by Viral Factors
Mahon, C., Krogan, N., Craik, C., & Pick, E. (2014) · Biomolecules · doi:10.3390/biom4040897 · Cited by 101 · see citing works
Self-citationThe Impact of Mass Spectrometry–Based Proteomics on Fundamental Discoveries in Virology
Greco, T. M., Diner, B. A., & Cristea, I. M. (2014) · Annual Review of Virology · doi:10.1146/annurev-virology-031413-085527 · Cited by 67 · see citing works
Dispersed Sites of HIV Vif-Dependent Polyubiquitination in the DNA Deaminase APOBEC3F
Albin, J. S., Anderson, J. S., Johnson, J. R., Harjes, E., Matsuo, H., Krogan, N. J., & Harris, R. S. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.01.010 · Cited by 25 · see citing works
Self-citationFrom serendipity to strategy: molecular glue degraders in cancer therapeutics
Darling, S., Bajrami, I., & West, S. C. (2025) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2025.2564068 · Cited by 10 · see citing works
“…viruses, including Hiv and HPv, have also employed this strategy in mammalian cells as they use both peptides and nucleotides to induce proximity between host e3 ligases and their selected targets to increase viral infectivity (Huh et al. 2007; Jäger et al. 2011; ito et al. 2023; li et al. 2023).”
- Authors
- Jäger, S., Kim, D. Y., Hultquist, J. F., Shindo, K., LaRue, R. S., Kwon, E., Li, M., Anderson, B. D., Yen, L., Stanley, D., Mahon, C., Kane, J., Franks-Skiba, K., Cimermancic, P., Burlingame, A., Sali, A., Craik, C. S., Harris, R. S., Gross, J. D., & Krogan, N. J.
- Affiliations
- University of California, San Francisco (US)
- University of Minnesota (US)
- QB3 (US)
- Corresponding author
- Harris, Reuben S.
- Gross, John D.
- Krogan, Nevan J.
- ORCID
- Venue
- Nature
- Published
- 2011-12-21
- Volume
- 481
- Issue
- 7381
- Pages
- 371-375
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3310910
- OpenAlex
- W2075049040
- Cited by
- 352
- References
- 28
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 14 · 2023: 16 · 2022: 16 · 2021: 26 · 2020: 17 · 2019: 26 · 2018: 27 · 2017: 29 · 2016: 29 · 2015: 27 · 2014: 38 · 2013: 34 · 2012: 30
- FWCI
- 13.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute of General Medical Sciences (P50GM082250, P50GM081879, R01GM078360, P41GM103481, P01GM091743)
- National Institute of Allergy and Infectious Diseases (R01AI064046, P01AI090935, T32AI083196)
- National Center for Research Resources (P41RR001614, U54RR022220)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- CBFβ, Vif, APOBEC3G, HIV-1, host restriction factors, polyubiquitination, protein degradation, HIV-1 infectivity, APOBEC3A, simian immunodeficiency virus, antiviral drug targets, Runx transcription factors
- MeSH terms
- APOBEC-3G Deaminase, Affinity Labels, Animals, Cytidine Deaminase, Genetic Complementation Test, Humans, Macaca mulatta, Models, Biological, Protein Binding, Mass Spectrometry, Virus Replication, Simian Immunodeficiency Virus, HIV-1, HIV Infections, Gene Products, vif, Jurkat Cells, Ubiquitin-Protein Ligases, Cullin Proteins, Core Binding Factor beta Subunit, vif Gene Products, Human Immunodeficiency Virus, Ubiquitination, Host-Pathogen Interactions, Gene Knockdown Techniques, HEK293 Cells, Proteolysis
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
