New map of protein interactions could direct future antiviral research
pathogens and humans could help explain how viruses and bacteria
manage to trick victim cells into carrying out their dirty work.
The research confirms existing suspicions about the different mechanisms used by pathogens, and it is hoped the technique could highlight key proteins to target with antiviral and antibacterial drugs. Pathogens often attack human cells using protein messengers, which bind to human proteins within the cell, relaying false messages that disrupt normal activity and force the cell to carry out tasks for the pathogen's own gain. A lot of research has investigated these different interactions, but until now the work has been contained within separate research papers or databases, with few links drawn between the different results. Now a team from the Virginia Bioinformatics Institute (VBI) and the Department of Computer Science at Virginia Tech have used a topological technique to create a map that demonstrated how each human protein interacts with each pathogen protein. Overall, the group drew together information from six databases, covering about 190 pathogens with a total of 10,477 human-pathogen protein interactions. The team also drew a map that showed the ways the different human proteins interact amongst themselves, to see how if these internal relationships correlate with the proteins most targeted by pathogens. By analysing common occurrences between these two maps, the researchers found that, within the human protein network, either hubs - proteins which connect with many other proteins - or bottlenecks, which lie on the shortest connections between two nodes, are the most likely human proteins to be targeted. "Since hubs and bottlenecks may both be critical proteins in a human cell's activities, it seems the pathogens have evolved to interact with these to gain better access and control of the cell," Dr T Murali, one of the researchers, told LabTechnologist.com. It was possible that these results could simply be a statistical consequence of the extent to which each protein had been studied, so the team performed statistical tests to ensure that the results really did reflect the activity of the proteins. The researchers then probed their maps more deeply, this time concentrating on the human proteins that interact with at least two viral or bacterial proteins, to see if there were any common characteristics in the functions these proteins performed within the cell. "We found that a number of the human proteins that interact with two or more pathogen proteins are central to the human cell cycle," said Murali. "We also found that these human proteins typically regulate cell death." It is thought that this prevents the cell from killing itself before the virus has had chance to replicate. In addition to providing its own conclusions, the maps created in this research will be available for other researchers to interrogate for their own work. In the past antiviral drugs had targeted the pathogens proteins, but new research suggests it may be possible to target the human proteins instead, and the team's maps could help direct future researchers to the best candidates. "There is talk about the possibility of developing antiviral drugs that inhibit the infection pathways by binding to the human proteins," explains Matt Dyer, the lead author of the paper. "We are interested in using these maps to identify the antiviral targets."
