Global landscape of HIV-human protein complexes.

Abstract

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.

• Authors: Stefanie Jäger, Peter Cimermancic, Natali Gulbahce, Jeffrey R Johnson, Kathryn E McGovern, Starlynn C Clarke, Michael Shales, Gaelle Mercenne, Lars Pache, Kathy Li, Hilda Hernandez, Gwendolyn M Jang, Shoshannah L Roth, Eyal Akiva, John Marlett, Melanie Stephens, Iván D'Orso, Jason Fernandes, Marie Fahey, Cathal Mahon, Anthony J O'Donoghue, Aleksandar Todorovic, John H Morris, David A Maltby, Tom Alber, Gerard Cagney, Frederic D Bushman, John A Young, Sumit K Chanda, Wesley I Sundquist, Tanja Kortemme, Ryan D Hernandez, Charles S Craik, Alma Burlingame, Andrej Sali, Alan D Frankel, Nevan J Krogan
• Journal: Nature (Nature) Vol. 481 Issue 7381 Pg. 365-70 (Dec 21 2011) ISSN: 1476-4687 [Electronic] England
• PMID: 22190034 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Affinity Labels
• EIF3D protein, human
• Eukaryotic Initiation Factor-3
• Human Immunodeficiency Virus Proteins
• HIV Protease

Topics

• Affinity Labels
• Amino Acid Sequence
• Conserved Sequence
• Eukaryotic Initiation Factor-3 (chemistry, metabolism)
• HEK293 Cells
• HIV Infections (metabolism, virology)
• HIV Protease (metabolism)
• HIV-1 (chemistry, metabolism, physiology)
• Host-Pathogen Interactions
• Human Immunodeficiency Virus Proteins (analysis, chemistry, isolation & purification, metabolism)
• Humans
• Immunoprecipitation
• Jurkat Cells
• Mass Spectrometry
• Protein Binding
• Protein Interaction Mapping (methods)
• Protein Interaction Maps (physiology)
• Reproducibility of Results
• Virus Replication