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Identifying potential survival strategies of HIV-1 through virus-host protein interaction networks.

van Dijk D, Ertaylan G, Boucher CA, Sloot PM - BMC Syst Biol (2010)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Computational Science, University of Amsterdam, Sciencepark 107, 1098 XG Amsterdam, The Netherlands. d.vandijk@uva.nl

ABSTRACT

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.

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Diagram representing the rewiring method used by the randomization algorithm. Two random edges are chosen and either the sources or the targets are switched with equal probability.
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Figure 6: Diagram representing the rewiring method used by the randomization algorithm. Two random edges are chosen and either the sources or the targets are switched with equal probability.

Mentions: The motif analysis was carried out on the regulatory and activation/inhibition subnetworks (inferred from the HIV-1 Human protein interaction network) by comparing the subnetworks with one thousand randomized networks, which were created by randomly rewiring the original networks (see Figure 6 and section Methods for details on the rewiring algorithm). This resulted in a number of significant motifs. In Figure 7 a selection (see additional file 12 for the complete table) of motifs are listed that were found to be significant (Zscore > 2, Pvalue < 0.02). Next we describe the types of motifs found.


Identifying potential survival strategies of HIV-1 through virus-host protein interaction networks.

van Dijk D, Ertaylan G, Boucher CA, Sloot PM - BMC Syst Biol (2010)

Diagram representing the rewiring method used by the randomization algorithm. Two random edges are chosen and either the sources or the targets are switched with equal probability.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2913931&req=5

Figure 6: Diagram representing the rewiring method used by the randomization algorithm. Two random edges are chosen and either the sources or the targets are switched with equal probability.
Mentions: The motif analysis was carried out on the regulatory and activation/inhibition subnetworks (inferred from the HIV-1 Human protein interaction network) by comparing the subnetworks with one thousand randomized networks, which were created by randomly rewiring the original networks (see Figure 6 and section Methods for details on the rewiring algorithm). This resulted in a number of significant motifs. In Figure 7 a selection (see additional file 12 for the complete table) of motifs are listed that were found to be significant (Zscore > 2, Pvalue < 0.02). Next we describe the types of motifs found.

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Computational Science, University of Amsterdam, Sciencepark 107, 1098 XG Amsterdam, The Netherlands. d.vandijk@uva.nl

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus