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Global landscape of HIV–human protein complexes


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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Figure 1: Affinity purification of HIV-1 proteins, analysis and scoring of mass spectrometry data.
Figure 2: Comparison of PPI data with other HIV data sets.
Figure 3: Network representation of the HIV–human PPIs.
Figure 4: eIF3d is cleaved by HIV-1 PR and inhibits 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.

Author information

Authors and Affiliations



S.J. generated the protein–protein interaction map; P.C. developed the MiST scoring system; N.G., M. Shales, E.A., M.F., J.H.M., J.R.J. and R.D.H. provided computational support; K.E.M., K.L., J.R.J., H.H., G.M.J., I.D., J.F. and D.A.M. provided experimental support; S.J., S.C.C., A.J.O. and A.T. characterized the PR–eIF3d interaction; S.J., G.M.J., C.M. and G.M. confirmed the interactions by immunoprecipitation/western blot; L.P., S.L.R., J.M. and M. Stephens used RNAi for functional verification; T.A., G.C., F.D.B., J.A.Y., S.K.C., W.I.S., T.K., R.D.H., C.S.C., A.B., A.S., A.D.F. and N.J.K. supervised the research; and S.J., P.C., A.S. and N.J.K. wrote the manuscript.

Corresponding author

Correspondence to Nevan J. Krogan.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

The file contains Supplementary Figures 1-20 with legends, Supplementary Tables 1-14, Supplementary Methods, a Supplementary Discussion and Supplementary References. (PDF 5928 kb)

Supplementary Data 1

The data shows raw MS data. (XLS 10886 kb)

Supplementary Data 2

The data shows three components used for MiST scoring. (XLS 1860 kb)

Supplementary Data 3

The data shows MiST scored MS data (>0.75 and full list). (XLS 1619 kb)

Supplementary Data 4

The data shows functional enrichment of host factors. (XLS 223 kb)

Supplementary Data 5

The data shows VirusMint PPIs. (XLS 115 kb)

Supplementary Data 6

The data shows overlap of VirusMint with all MiST scores. (XLS 28 kb)

Supplementary Data 7

The data shows published RNAi screens. (XLS 109 kb)

Supplementary Data 8

The data shows overlap of RNAi screens with all MiST scores. (XLS 210 kb)

Supplementary Data 9

The data shows human-human PPIs used in HIV-human network representation. (XLS 44 kb)

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Jäger, S., Cimermancic, P., Gulbahce, N. et al. Global landscape of HIV–human protein complexes. Nature 481, 365–370 (2012).

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