Title: Virus interactions with human signal transduction pathways

Authors: Zhongming Zhao, Junfeng Xia, Oznur Tastan, Irtisha Singh, Meghana Kshirsagar, Jaime Carbonell, Judith Klein-Seetharaman

Addresses: Departments of Biomedical Informatics, Psychiatry, and Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA. ' Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA. ' Language Technologies Institute, School of Computer Science, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA. ' Department of Structural Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. ' Language Technologies Institute, School of Computer Science, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA. ' Language Technologies Institute, Computer Science Department, Machine Learning Department and Lane Center for Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA. ' Department of Structural Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA

Abstract: Viruses depend on their hosts at every stage of their life cycles and must therefore communicate with them via Protein-Protein Interactions (PPIs). To investigate the mechanisms of communication by different viruses, we overlay reported pairwise human-virus PPIs on human signalling pathways. Of 671 pathways obtained from NCI and Reactome databases, 355 are potentially targeted by at least one virus. The majority of pathways are linked to more than one virus. We find evidence supporting the hypothesis that viruses often interact with different proteins depending on the targeted pathway. Pathway analysis indicates overrepresentation of some pathways targeted by viruses. The merged network of the most statistically significant pathways shows several centrally located proteins, which are also hub proteins. Generally, hub proteins are targeted more frequently by viruses. Numerous proteins in virus-targeted pathways are known drug targets, suggesting that these might be exploited as potential new approaches to treatments against multiple viruses.

Keywords: systems biology; protein-protein interaction; PPI networks; host-pathogen interactions; protein function; signal transduction; human immunodeficiency virus-1; human papillomavirus; bovine papillomavirus; Epstein-Barr virus; human herpesvirus; virus interactions; human signalling pathways; multiple viruses.

DOI: 10.1504/IJCBDD.2011.038658

International Journal of Computational Biology and Drug Design, 2011 Vol.4 No.1, pp.83 - 105

Available online: 17 Feb 2011 *

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