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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We thank A. Choi, Z. Rizvi and E. Kwon for cloning of human genes and J. Cate for purified eIF3. We also thank J. Gross, R. Andino, R. Harris, M. Daugherty and members of the Krogan lab for discussion. This research was funded by grants from QB3@UCSF and the National Institutes of Health (P50 GM082250 to N.J.K., A.D.F., C.S.C. and T.A.; P01 AI090935 to N.J.K., S.K.C., J.A.Y. and F.D.B.; P50 GM081879 to N.J.K. and A.B.; P50 GM082545 to W.I.S.; P41RR001614 to A.B.; U54 RR022220 to A.S.; P01 GM073732-05 to A.T.; CHRP-ID08-TBI-063 to S.K.C.; P41 RR001081 to J.H.M.) and from the Nomis Foundation (to J.A.Y.). N.J.K. is a Searle Scholar and a Keck Young Investigator.
The data shows raw MS data.
The data shows three components used for MiST scoring.
The data shows MiST scored MS data (>0.75 and full list).
The data shows functional enrichment of host factors.
The data shows VirusMint PPIs.
The data shows overlap of VirusMint with all MiST scores.
The data shows published RNAi screens.
The data shows overlap of RNAi screens with all MiST scores.
The data shows human-human PPIs used in HIV-human network representation.