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

Motivation Beside socio-economic issues, coronavirus pandemic COVID-19, the infectious disease caused by the newly discovered coronavirus SARS-CoV-2, has caused a deep impact in the scientific community, that has considerably increased its effort to discover the infection strategies of the new virus. Among the extensive and crucial research that has been carried out in the last months, the analysis of the virus-host relationship plays an important role in drug discovery. Virus-host protein-protein interactions are the active agents in virus replication, and the analysis of virus-host protein-protein interaction networks is fundamental to the study of the virus-host relationship. Results We have adapted and implemented a recent integer linear programming model for protein-protein interaction network alignment to virus-host networks, and obtained a consensus alignment of the SARS-CoV-1 and SARS-CoV-2 virus-host protein-protein interaction networks. Despite the lack of shared human proteins in these virus-host networks, and the low number of preserved virus-host interactions, the consensus alignment revealed aligned human proteins that share a function related to viral infection, as well as human proteins of high functional similarity that interact with SARS-CoV-1 and SARS-CoV-2 proteins, whose alignment would preserve these virus-host interactions.

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Alignment of biological networks by integer linear programming: virus-host protein-protein interaction networks

BMC Bioinformatics ◽

10.1186/s12859-020-03733-w ◽

2020 ◽

Vol 21 (S6) ◽

Cited By ~ 1

Author(s):

Mercè Llabrés ◽

Gabriel Riera ◽

Francesc Rosselló ◽

Gabriel Valiente

Keyword(s):

Linear Programming ◽

Integer Linear Programming ◽

Protein Interaction ◽

Software Tools ◽

Protein Interaction Networks ◽

Interaction Networks ◽

Host Protein ◽

Protein Protein Interaction ◽

Programming Software ◽

Protein Protein Interaction Networks

Abstract Background The alignment of protein-protein interaction networks was recently formulated as an integer quadratic programming problem, along with a linearization that can be solved by integer linear programming software tools. However, the resulting integer linear program has a huge number of variables and constraints, rendering it of no practical use. Results We present a compact integer linear programming reformulation of the protein-protein interaction network alignment problem, which can be solved using state-of-the-art mathematical modeling and integer linear programming software tools, along with empirical results showing that small biological networks, such as virus-host protein-protein interaction networks, can be aligned in a reasonable amount of time on a personal computer and the resulting alignments are structurally coherent and biologically meaningful. Conclusions The implementation of the integer linear programming reformulation using current mathematical modeling and integer linear programming software tools provided biologically meaningful alignments of virus-host protein-protein interaction networks.

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Hacking the Cell: Network Intrusion and Exploitation by Adenovirus E1A

mBio ◽

10.1128/mbio.00390-18 ◽

2018 ◽

Vol 9 (3) ◽

Cited By ~ 31

Author(s):

Cason R. King ◽

Ali Zhang ◽

Tanner M. Tessier ◽

Steven F. Gameiro ◽

Joe S. Mymryk

Keyword(s):

Protein Interaction ◽

Protein Interactions ◽

Molecular Basis ◽

Human Adenovirus ◽

Protein Interaction Networks ◽

Interaction Networks ◽

Host Protein ◽

Viral Control ◽

Adenovirus E1a ◽

Network Intrusion

ABSTRACTAs obligate intracellular parasites, viruses are dependent on their infected hosts for survival. Consequently, viruses are under enormous selective pressure to utilize available cellular components and processes to their own advantage. As most, if not all, cellular activities are regulated at some level via protein interactions, host protein interaction networks are particularly vulnerable to viral exploitation. Indeed, viral proteins frequently target highly connected “hub” proteins to “hack” the cellular network, defining the molecular basis for viral control over the host. This widespread and successful strategy of network intrusion and exploitation has evolved convergently among numerous genetically distinct viruses as a result of the endless evolutionary arms race between pathogens and hosts. Here we examine the means by which a particularly well-connected viral hub protein, human adenovirus E1A, compromises and exploits the vulnerabilities of eukaryotic protein interaction networks. Importantly, these interactions identify critical regulatory hubs in the human proteome and help define the molecular basis of their function.

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Alignment of virus-host protein-protein interaction networks by integer linear programming: SARS-CoV-2

10.1101/2020.07.07.191247 ◽

2020 ◽

Author(s):

Mercè Llabrés ◽

Gabriel Valiente

Keyword(s):

Linear Programming ◽

Protein Interaction ◽

Protein Interaction Networks ◽

Interaction Networks ◽

Host Protein ◽

Host Interactions ◽

Protein Protein Interaction ◽

Human Proteins ◽

Consensus Alignment ◽

Protein Protein Interaction Networks

AbstractBeside socio-economic issues, coronavirus pandemic COVID-19, the infectious disease caused by the newly discovered coronavirus SARS-CoV-2, has caused a deep impact in the scientific community, that has considerably increased its effort to discover the infection strategies of the new virus. Among the extensive and crucial research that has been carried out in the last few months, the analysis of the virus-host relationship plays an important role in drug discovery. Virus-host protein-protein interactions are the active agents in virus replication, and the analysis of virus-host protein-protein interaction networks is fundamental to the study of the virus-host relationship. We have adapted and implemented a recent integer linear programming model for protein-protein interaction network alignment to virus-host networks, and obtained a consensus alignment of the SARS-CoV-1 and SARS-CoV-2 virus-host protein-protein interaction networks. Despite the lack of shared human proteins in these virus-host networks and the low number of preserved virus-host interactions, the consensus alignment revealed aligned human proteins that share a function related to viral infection, as well as human proteins of high functional similarity that interact with SARS-CoV-1 and SARS-CoV-2 proteins, whose alignment would preserve these virus-host interactions.

Download Full-text