The Landscape of Human Proteins Interacting with Viruses and Other Pathogens

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. Many pathogens, such as viruses and bacteria, cause disease in humans. Pathogen infections result in illness and death for millions of people each year. Pathogens communicate with human cells through physical interactions with various human proteins on the surface of the cell and within the interior of the cell. These interactions allow the pathogen to enter the host cell, manipulate important cellular processes, multiply, and invade other cells. In this paper, we compare interactions between human and pathogen proteins from 190 different pathogens to provide important insights into strategies used by pathogens to infect human cells. We show that both viral and bacterial proteins interact with human proteins that themselves interact with many human proteins or with human proteins that lie on many communication channels between other human proteins. Pathogens may have evolved to interact with these human proteins since they may control critical human cellular process. We also demonstrate that many viruses share common infection strategies, e.g., lengthening particular stages of the cell cycle, controlling programmed cell death, and interacting with the nuclear membrane to transfer viral genetic material into and out of the nucleus. Such studies may help us better understand the process of infection and identify better strategies to prevent or cure infection.