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About the Authors:
Stefan Wuchty
* E-mail: [email protected]
Affiliation: National Center of Biotechnology Information, National Institutes of Health, Bethesda, Maryland, United States of America
Geoffrey Siwo
Affiliation: Eck Institute for Global Health, Department of Biology, University of Notre Dame, Notre Dame, Indiana, United States of America
Michael T. Ferdig
Affiliation: Eck Institute for Global Health, Department of Biology, University of Notre Dame, Notre Dame, Indiana, United States of America
Introduction
The determination of webs of protein interactions [1], [2], [3], [4] and protein complexes [5], [6], [7], [8], [9] in many different single and multi-cellular organisms progresses at a fast pace, peaking in attempts to determine the human interactome in various ways [10], [11], [12], [13], [14]. Although such webs of intracellular interactions are increasingly well characterized, little is known about large-scale maps of protein interactions between cells. Therefore, the investigation of host-pathogen interactions is a crucial step toward a thorough understanding of an organism's pathogenesis, providing an essential foundation for the development of effective therapeutic and prevention strategies to combat diseases. Uetz et al. released the first small map of computationally inferred physical protein interactions between the human host and the Kaposi-Sarcoma associated Herpesvirus (KSHV) as well as the Varicella Zoster-Virus (VZV) [15]. In a different approach, Calderwood et al. [16] experimentally determined a map of physical protein interactions between the Epstein-Barr-Virus and the human host. Recently, Bandyopadhyay et al. [17], identified subnetworks of virus-host proteins that are expressed at different stages of the HIV-infection and Dyer et al. compared experimentally known interactions of different viruses with the human host [18]. Brass et al. utilized a comprehensive large scale-screen of siRNAs to identify HIV dependency factor proteins (HDF). Although these proteins do not directly interact with viral proteins, they play an indirect, yet important role in the infection process of HIV [19].
Here, we pooled experimentally verified interactions between HIV-1 and human proteins, along with a set of HIV-dependency factor proteins (HDF), to investigate the topology of interactions between viral and host proteins on a large scale. We found that targeted and HDF proteins appeared predominantly in rich-clubs, allowing the virus to take control of the human host by reaching protein pathways and diversified cellular functions in a pronounced and focused way. Although HIV-1...