The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Global landscape of HIV–human protein complexes
Open accessAbstract
Human immunodeficiency virus (HIV) has a small genome and therefore relies heavily on the host cellular machinery to replicate. Identifying which host proteins and complexes come into physical contact with the viral proteins is crucial for a comprehensive understanding of how HIV rewires the host's cellular machinery during the course of infection. Here we report the use of affinity tagging and purification mass spectrometry to determine systematically the physical interactions of all 18 HIV-1 proteins and polyproteins with host proteins in two different human cell lines (HEK293 and Jurkat). Using a quantitative scoring system that we call MiST, we identified with high confidence 497 HIV-human protein-protein interactions involving 435 individual human proteins, with ∼40% of the interactions being identified in both cell types. We found that the host proteins hijacked by HIV, especially those found interacting in both cell types, are highly conserved across primates. We uncovered a number of host complexes targeted by viral proteins, including the finding that HIV protease cleaves eIF3d, a subunit of eukaryotic translation initiation factor 3. This host protein is one of eleven identified in this analysis that act to inhibit HIV replication. This data set facilitates a more comprehensive and detailed understanding of how the host machinery is manipulated during the course of HIV infection.
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In the citing paper
“In recent years, cellular factors interacting with HIV-1 proteins and RNAs have been identified using proteomic approaches (122-124).”
From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [122]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“The MA domain of Gag is a major interaction partner of the MSC, and MA has also been reported to interact with a few non-MSC ARSs (Table 1) (122).”
From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [122]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“| Interacts with HIV-1 5ЈUTR | ArgRS a , EPRS a | 122 |”
From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [122]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“| Interacts with RSV 5ЈUTR | LysRS a , SerRS2 | 122 |”
From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [122]
Experimental — accuracy not yet measuredIn the citing paper
“For example, in a large-scale interactome study, all the viral proteins encoded by the HIV genome were individually expressed in 293 and Jurkat cells and subjected to TAP AP-MS analysis (61).”
From The Impact of Mass Spectrometry–Based Proteomics on Fundamental Discoveries in Virology (2014) · cites this paper as [61]
In the citing paper
“Moreover, 97 of 127 selected interactions were confirmed by reciprocal isolations, highlighting the confidence of this data set.”
From The Impact of Mass Spectrometry–Based Proteomics on Fundamental Discoveries in Virology (2014) · cites this paper as [61]
In the citing paper
“Almost 200 interactions were identified in both cell types.”
From The Impact of Mass Spectrometry–Based Proteomics on Fundamental Discoveries in Virology (2014) · cites this paper as [61]
In the citing paper
“Another interaction specificity predictor, MiST, distinguished high-confidence virus-host protein interactions of epitope-tagged HIV proteins individually expressed in human cells (61).”
From The Impact of Mass Spectrometry–Based Proteomics on Fundamental Discoveries in Virology (2014) · cites this paper as [61]
In the citing paper
“Using AP-MS, nearly 500 specific HIV–host protein interactions were identified”
From Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection (2016) · cites this paper as [54]
In the citing paper
“When eIF3d was knocked down via RNA interference, an additional 10 host factors were found to hinder HIV replication by means of virus–host protein interactions.”
From Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection (2016) · cites this paper as [54]
In the citing paper
“approximately 40% of which were prevalent in both cell types.”
From Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection (2016) · cites this paper as [54]
In the citing paper
“the observed overlap in interactions between HEK293 and Jurkat cells was limited.”
From Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection (2016) · cites this paper as [54]
In the citing paper
“A host subunit of eukaryotic translation initiation factor 3, eIF3d, was found to be targeted for cleavage by an HIV protease.”
From Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection (2016) · cites this paper as [54]
In the citing paper
“the comparison of HEK293 cells with Jurkat cells, which are immortalized CD4+ T cells commonly used in HIV-1 studies, helped to substantiate the potential biological relevance of the subset of protein associations identified in both human cell types.”
From Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection (2016) · cites this paper as [54]
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Citations
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Metadata
- Authors
- Jäger, S., Cimermancic, P., Gulbahce, N., Johnson, J. R., McGovern, K. E., Clarke, S. C., Shales, M., Mercenne, G., Pache, L., Li, K., Hernandez, H., Jang, G. M., Roth, S. L., Akiva, E., Marlett, J., Stephens, M., D’Orso, I., Fernandes, J., Fahey, M., Mahon, C., O’Donoghue, A. J., Todorovic, A., Morris, J. H., Maltby, D. A., Alber, T., Cagney, G., Bushman, F. D., Young, J. A., Chanda, S. K., Sundquist, W. I., Kortemme, T., Hernandez, R. D., Craik, C. S., Burlingame, A., Sali, A., Frankel, A. D., & Krogan, N. J.
- Affiliations
- University of California, San Francisco (US)
- QB3 (US)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- University of Pennsylvania (US)
- Salk Institute for Biological Studies (US)
- University of California, Berkeley (US)
- University College Dublin (IE)
- University of Utah (US)
- Corresponding author
- Krogan, Nevan J.
- ORCID
- Jäger, Stefanie
- Gulbahce, Natali
- Johnson, Jeffrey R.
- McGovern, Kathryn E.
- Clarke, Starlynn C.
- Pache, Lars
- Li, Kathy
- Akiva, Eyal
- D’Orso, Iván
- Fernandes, Jason
- Fahey, Marie
- Mahon, Cathal
- O’Donoghue, Anthony J.
- Morris, John H.
- Cagney, Gerard
- Bushman, Frederic D.
- Young, John A.
- Chanda, Sumit K.
- Sundquist, Wesley I.
- Kortemme, Tanja
- Hernandez, Ryan D.
- Craik, Charles S.
- Burlingame, Alma
- Frankel, Alan D.
- Krogan, Nevan J.
- Venue
- Nature
- Published
- 2011-12-21
- Volume
- 481
- Issue
- 7381
- Pages
- 365-370
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3310911
- OpenAlex
- W1996076856
- Cited by
- 731
- References
- 29
- Citations by year
- 2026: 22 · 2025: 25 · 2024: 37 · 2023: 41 · 2022: 46 · 2021: 59 · 2020: 44 · 2019: 51 · 2018: 50 · 2017: 47 · 2016: 59 · 2015: 62 · 2014: 67 · 2013: 58 · 2012: 62
- FWCI
- 23.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (P50GM082250, P50GM081879, P50GM082545, P41GM103481, P01GM073732)
- National Institute of Allergy and Infectious Diseases (P01AI090935)
- National Center for Research Resources (P41RR001614, P41RR001081, U54RR022220)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Keywords
- HIV-1, host-virus protein interaction, protein-protein interaction, HIV replication, integrase, eIF3, primate conservation
- MeSH terms
- Affinity Labels, Amino Acid Sequence, Humans, Protein Binding, Mass Spectrometry, Virus Replication, Reproducibility of Results, HIV-1, HIV Infections, HIV Protease, Conserved Sequence, Jurkat Cells, Protein Interaction Mapping, Eukaryotic Initiation Factor-3, Immunoprecipitation, Human Immunodeficiency Virus Proteins, Host-Pathogen Interactions, HEK293 Cells, Protein Interaction Maps
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