Abstract
Infectious diseases result in millions of deaths each year. Mechanisms of infection have been studied in detail for many pathogens. However, many questions are relatively unexplored. What are the properties of human proteins that interact with pathogens? Do pathogens interact with certain functional classes of human proteins? Which infection mechanisms and pathways are commonly triggered by multiple pathogens? In this paper, to our knowledge, we provide the first study of the landscape of human proteins interacting with pathogens. We integrate human–pathogen protein–protein interactions (PPIs) for 190 pathogen strains from seven public databases. Nearly all of the 10,477 human-pathogen PPIs are for viral systems (98.3%), with the majority belonging to the human–HIV system (77.9%). We find that both viral and bacterial pathogens tend to interact with hubs (proteins with many interacting partners) and bottlenecks (proteins that are central to many paths in the network) in the human PPI network. We construct separate sets of human proteins interacting with bacterial pathogens, viral pathogens, and those interacting with multiple bacteria and with multiple viruses. Gene Ontology functions enriched in these sets reveal a number of processes, such as cell cycle regulation, nuclear transport, and immune response that participate in interactions with different pathogens. Our results provide the first global view of strategies used by pathogens to subvert human cellular processes and infect human cells. Supplementary data accompanying this paper is available at http://staff.vbi.vt.edu/dyermd/publications/dyer2008a.html.
Highlights
Infectious diseases result in millions of deaths each year
What are the properties of human proteins that interact with pathogens? Do pathogens interact with certain functional classes of human proteins? Which infection mechanisms and pathways are commonly triggered by multiple pathogens? A significant hurdle to such global cross-pathogen comparisons has been the shortage of largescale datasets of interactions between host and pathogen proteins
Human Proteins Targeted by Multiple Bacterial Pathogens the number of human-bacteria protein-protein interactions (PPIs) gathered in this study is small, our methods identified an important subset of human proteins enriched for functions involved in immune response and interacting with multiple bacterial pathogen groups
Summary
Millions of dollars are spent annually to better understand how pathogens infect their hosts and to identify potential targets for therapeutics. An important aspect of any hostpathogen system is the mechanism by which a pathogen is able to invade a host cell. Within these complex systems, protein-protein interactions (PPIs) between surface proteins form the foundation of communication between a host and a pathogen and play a vital role in initiating infection [1]. What are the properties of human proteins that interact with pathogens? Recent efforts to include host-pathogen PPIs in public databases have made it easier to acquire the data needed to address these important questions
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