Scientists at Virginia Tech say that they have provided the first global analysis of human proteins interacting with viral and bacterial proteins.
The investigators examined publicly available experimental data for 190 different pathogens that comprise 10,477 interactions between human and pathogen proteins. This provided a network map of human proteins interfacing with proteins in different pathogens. 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. Findings of the study include a 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, report the investigators. 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 global study also suggests that many viruses share similar strategies to control the human cell cycle, regulate programmed cell death, and transport viral genetic material across the nuclear membrane in the human cell,” says T. M. Murali, Ph.D., an assistant professor in the department of computer science.
The research is published online on February 15 in PLoS Pathogens.