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 spectrometry1, 2, 3 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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- Supplementary Information (5.7M)
The file contains Supplementary Figures 1-20 with legends, Supplementary Tables 1-14, Supplementary Methods, a Supplementary Discussion and Supplementary References.
- Supplementary Data 1 (10.6M)
The data shows raw MS data.
- Supplementary Data 2 (1.8M)
The data shows three components used for MiST scoring.
- Supplementary Data 3 (1.5M)
The data shows MiST scored MS data (>0.75 and full list).
- Supplementary Data 4 (223K)
The data shows functional enrichment of host factors.
- Supplementary Data 5 (115K)
The data shows VirusMint PPIs.
- Supplementary Data 6 (28K)
The data shows overlap of VirusMint with all MiST scores.
- Supplementary Data 7 (109K)
The data shows published RNAi screens.
- Supplementary Data 8 (210K)
The data shows overlap of RNAi screens with all MiST scores.
- Supplementary Data 9 (44K)
The data shows human-human PPIs used in HIV-human network representation.