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Researchers Unveil Human-Pathogen Protein Interactions
March 12, 2008

Researchers at the Virginia Bioinformatics Institute and the Department of Computer Science at Virginia Tech have provided the first global analysis of human proteins interacting with viral proteins and proteins in other pathogens.

The scientists examined publicly available experimental data for 190 different pathogens that comprise 10,477 interactions between human and pathogen proteins. This approach provides a highly detailed network map of human proteins interfacing with proteins in different pathogens. The network of interactions was published recently in the journal PLoS Pathogens and reveals possible key intervention points for the future development of therapeutics against infectious diseases.

The researchers paid particular attention to two networks of human proteins – proteins that interact with at least two viral pathogens and proteins that interact with at least two bacterial pathogens. Gene ontology terms computed for both sets of proteins provided key information on the functions of the different proteins. Some of the striking findings of the study included a clear demonstration that pathogens preferentially interact with two classes of human proteins referred to as hubs and bottlenecks. Hubs are popular proteins that interact with many other proteins in the human protein interaction network. Bottlenecks are proteins that lie on many of the shortest paths in the network.

Pathogens appear to maximize their likelihood of success by targeting these high-impact, influential proteins during infection. In many cases, human proteins that mediate pathogen effects are proteins that are known to be involved in cancer pathways, for example, the transcription factor STAT1 or the tumor suppressor protein TP53. This finding suggests interesting parallels between pathogen infection and cancer and opens up future areas for research.

Institute researchers Matt Dyer and Bruno Sobral, and Department of Computer Science researcher T. M. Murali contributed to the paper, “The Landscape of Human Proteins Interacting with Viruses and other Pathogens.” The paper will be featured in the February 15th, 2008, edition of PLoS Pathogens 4(2): e32. doi:10.1371/journal.ppat.0040032. The work was supported by Department of Defense grant #DAAD 13-02-C-0018 and National Institute of Allergy and Infectious Diseases grant HHSN26620040035C awarded to Bruno Sobral.

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