Researchers at Georgia Tech are discovering how bacteriophages collectively decide whether to begin killing the host cell.
The research, published in the September 15 issue of the Biophysical Journal, shows that when multiple viruses infect a cell, this increases the number of viral genomes and therefore the overall level of viral gene expression. Changes in viral gene expression can have a dramatic nonlinear effect on gene networks that control whether viruses burst out of the host cell or enter a latent state.
“What has confounded the virology community for quite some time is the observation that the cell fate of a bacteria infected by a single virus can be dramatically different than that infected by two viruses,” said Joshua Weitz, an assistant professor in the School of Biology at the Georgia Institute of Technology. “Our study suggests that viruses can collectively decide whether or not to kill a host, and that individual viruses ‘talk’ to each other as a result of interactions between viral genomes and viral proteins they direct the infected host to produce.”
To study viral infections, Weitz teamed with postdoctoral fellow Yuriy Mileyko, graduate student Richard Joh and Eberhard Voit, who is a professor in the Wallace H. Coulter Department of Biomedical Engineering, the David D. Flanagan Chair Georgia Research Alliance Eminent Scholar in Biological Systems and director of the new Integrative BioSystems Institute at Georgia Tech.
Nearly all previous theoretical studies have claimed that switching between “lysis” and “latency” pathways depends on some change in environmental conditions or random chance. However, this new study suggests that the response to co-infection can be an evolvable feature of viral life history.
For this study, the researchers analyzed the decision circuit that determines whether a virus initially chooses the pathway that kills the host cell – called the lytic pathway – or the pathway where it remains dormant inside the host cell – called the lysogenic pathway.
When the lytic pathway is selected, the virus utilizes bacterial resources to replicate and then destroys the host cell, releasing new viruses that can infect other cells. In contrast, in the lysogenic pathway, the viral genome inserts itself into the bacterial genome and replicates along with it, while repressing viral genes that lead to lysis. The virus remains dormant until host conditions change, which can result in a switch to the lytic pathway.
Press release: Study Reveals How Multiple Viruses Can Determine Bacterial Cell Fate
Abstract: Collective Decision Making in Bacterial Viruses Biophysical Journal 95:2673-2680 (2008)