Identifying potential survival strategies of HIV-1 through virus-host protein interaction networks.
BACKGROUND
The National Institute of Allergy and Infectious Diseases has launched the HIV-1 Human Protein Interaction Database in an effort to catalogue all published interactions between HIV-1 and human proteins. In order to systematically investigate these interactions functionally and dynamically, we have constructed an HIV-1 human protein interaction network. This network was analyzed for important proteins and processes that are specific for the HIV life-cycle. In order to expose viral strategies, network motif analysis was carried out showing reoccurring patterns in virus-host dynamics.


RESULTS
Our analyses show that human proteins interacting with HIV form a densely connected and central sub-network within the total human protein interaction network. The evaluation of this sub-network for connectivity and centrality resulted in a set of proteins essential for the HIV life-cycle. Remarkably, we were able to associate proteins involved in RNA polymerase II transcription with hubs and proteasome formation with bottlenecks. Inferred network motifs show significant over-representation of positive and negative feedback patterns between virus and host. Strikingly, such patterns have never been reported in combined virus-host systems.


CONCLUSIONS
HIV infection results in a reprioritization of cellular processes reflected by an increase in the relative importance of transcriptional machinery and proteasome formation. We conclude that during the evolution of HIV, some patterns of interaction have been selected for resulting in a system where virus proteins preferably interact with central human proteins for direct control and with proteasomal proteins for indirect control over the cellular processes. Finally, the patterns described by network motifs illustrate how virus and host interact with one another.
van Dijk
David
D
Computational Science, University of Amsterdam, Sciencepark 107, 1098 XG Amsterdam, The Netherlands. d.vandijk@uva.nl
Ertaylan
Gokhan
G
Boucher
Charles Ab
CA
Sloot
Peter Ma
PM
D030562:Databases, Protein; D025461:Feedback, Physiological / Q000502:physiology*; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000378:metabolism* / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D025941:Protein Interaction Mapping / Q000379:methods*; D011506:Proteins / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism
D011506:Proteins; D012319:RNA Polymerase II