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An integrated map of HIV-human protein complexes that facilitate viral infection.

Emig-Agius D, Olivieri K, Pache L, Shih HL, Pustovalova O, Bessarabova M, Young JA, Chanda SK, Ideker T - PLoS ONE (2014)

Bottom Line: Recent proteomic and genetic studies have aimed to identify a complete network of interactions between HIV and human proteins and genes.This HIV-human interaction network provides invaluable information as to how HIV exploits the host machinery and can be used as a starting point for further functional analyses.Thus, our HIV-human protein complex map provides a significant resource of potential HIV-host interactions for further study.

View Article: PubMed Central - PubMed

Affiliation: Departments of Medicine and Bioengineering, University of California at San Diego, La Jolla, California, United States of America; IP&Science, Thomson Reuters Scientific Inc., Carlsbad, California, United States of America.

ABSTRACT
Recent proteomic and genetic studies have aimed to identify a complete network of interactions between HIV and human proteins and genes. This HIV-human interaction network provides invaluable information as to how HIV exploits the host machinery and can be used as a starting point for further functional analyses. We integrated this network with complementary datasets of protein function and interaction to nominate human protein complexes with likely roles in viral infection. Based on our approach we identified a global map of 40 HIV-human protein complexes with putative roles in HIV infection, some of which are involved in DNA replication and repair, transcription, translation, and cytoskeletal regulation. Targeted RNAi screens were used to validate several proteins and complexes for functional impact on viral infection. Thus, our HIV-human protein complex map provides a significant resource of potential HIV-host interactions for further study.

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Map of HIV-human protein complexes.40 identified human protein complexes are shown together with the HIV protein targeting the complex. Green rectangles correspond to HIV proteins. Human complexes are shown as ellipses. A color gradient from red (high) to yellow (low) indicates the average rank of the complex in the APMS- and RNAi-propagations. Node size corresponds to number of subunits in the complex. Gray edges represent functional interactions between the human complexes; green edges are HIV-human interactions. Purple boxes indicate protein complexes that were selected for follow-up RNAi screens.
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pone-0096687-g004: Map of HIV-human protein complexes.40 identified human protein complexes are shown together with the HIV protein targeting the complex. Green rectangles correspond to HIV proteins. Human complexes are shown as ellipses. A color gradient from red (high) to yellow (low) indicates the average rank of the complex in the APMS- and RNAi-propagations. Node size corresponds to number of subunits in the complex. Gray edges represent functional interactions between the human complexes; green edges are HIV-human interactions. Purple boxes indicate protein complexes that were selected for follow-up RNAi screens.

Mentions: The prioritization of human HIV-dependency factors is an important first step towards understanding how HIV exploits the human cellular machinery. However, since proteins often perform their functions in concert, i.e. through the formation of protein complexes, we sought to analyze HIV-dependency factors at the complex level. Starting with the high-confidence RNAi-HIV set of 554 proteins resulting from the previously-described network propagation, we found that these proteins were significantly enriched for 40 protein complexes from the CORUM database [13]. Of these 40 complexes, 27 had not been reported in previous studies of HIV, while the remaining 13 complexes had been identified by at least one previously published analysis (Table 1). To create an HIV-human protein complex map, we assigned the interacting HIV protein with the highest interaction confidence to each complex (Fig. 4, Methods). In this map, 15 of 18 HIV proteins directly target human complexes and36 of the 40 complexes in the map have at least one subunit that directly interacts with HIV.


An integrated map of HIV-human protein complexes that facilitate viral infection.

Emig-Agius D, Olivieri K, Pache L, Shih HL, Pustovalova O, Bessarabova M, Young JA, Chanda SK, Ideker T - PLoS ONE (2014)

Map of HIV-human protein complexes.40 identified human protein complexes are shown together with the HIV protein targeting the complex. Green rectangles correspond to HIV proteins. Human complexes are shown as ellipses. A color gradient from red (high) to yellow (low) indicates the average rank of the complex in the APMS- and RNAi-propagations. Node size corresponds to number of subunits in the complex. Gray edges represent functional interactions between the human complexes; green edges are HIV-human interactions. Purple boxes indicate protein complexes that were selected for follow-up RNAi screens.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016004&req=5

pone-0096687-g004: Map of HIV-human protein complexes.40 identified human protein complexes are shown together with the HIV protein targeting the complex. Green rectangles correspond to HIV proteins. Human complexes are shown as ellipses. A color gradient from red (high) to yellow (low) indicates the average rank of the complex in the APMS- and RNAi-propagations. Node size corresponds to number of subunits in the complex. Gray edges represent functional interactions between the human complexes; green edges are HIV-human interactions. Purple boxes indicate protein complexes that were selected for follow-up RNAi screens.
Mentions: The prioritization of human HIV-dependency factors is an important first step towards understanding how HIV exploits the human cellular machinery. However, since proteins often perform their functions in concert, i.e. through the formation of protein complexes, we sought to analyze HIV-dependency factors at the complex level. Starting with the high-confidence RNAi-HIV set of 554 proteins resulting from the previously-described network propagation, we found that these proteins were significantly enriched for 40 protein complexes from the CORUM database [13]. Of these 40 complexes, 27 had not been reported in previous studies of HIV, while the remaining 13 complexes had been identified by at least one previously published analysis (Table 1). To create an HIV-human protein complex map, we assigned the interacting HIV protein with the highest interaction confidence to each complex (Fig. 4, Methods). In this map, 15 of 18 HIV proteins directly target human complexes and36 of the 40 complexes in the map have at least one subunit that directly interacts with HIV.

Bottom Line: Recent proteomic and genetic studies have aimed to identify a complete network of interactions between HIV and human proteins and genes.This HIV-human interaction network provides invaluable information as to how HIV exploits the host machinery and can be used as a starting point for further functional analyses.Thus, our HIV-human protein complex map provides a significant resource of potential HIV-host interactions for further study.

View Article: PubMed Central - PubMed

Affiliation: Departments of Medicine and Bioengineering, University of California at San Diego, La Jolla, California, United States of America; IP&Science, Thomson Reuters Scientific Inc., Carlsbad, California, United States of America.

ABSTRACT
Recent proteomic and genetic studies have aimed to identify a complete network of interactions between HIV and human proteins and genes. This HIV-human interaction network provides invaluable information as to how HIV exploits the host machinery and can be used as a starting point for further functional analyses. We integrated this network with complementary datasets of protein function and interaction to nominate human protein complexes with likely roles in viral infection. Based on our approach we identified a global map of 40 HIV-human protein complexes with putative roles in HIV infection, some of which are involved in DNA replication and repair, transcription, translation, and cytoskeletal regulation. Targeted RNAi screens were used to validate several proteins and complexes for functional impact on viral infection. Thus, our HIV-human protein complex map provides a significant resource of potential HIV-host interactions for further study.

Show MeSH
Related in: MedlinePlus