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.
The decision of the genetic circuit that controls whether a virus initially chooses lysis or lysogeny is not random. Instead, cell fate is controlled by the number of infecting viruses in a coordinated fashion, according to the new study, which was funded by the Defense Advanced Research Projects Agency, the National Science Foundation and the Burroughs Wellcome Fund.
"In the case of perhaps the most extensively studied bacteriophage, lambda phage, experimental evidence indicates that a single infecting phage leads to host cell death and viral release, whereas if two or more phages infect a host the outcome is typically latency," explained Weitz, who is a core member of the new Integrative BioSystems Institute at Georgia Tech. "We wanted to know why two viruses would behave differently than a single virus, given that the infecting viruses possess the same genetic decision circuit."
To find out, the researchers modeled the complex gene regulatory dynamics of the lysis-lysogeny switch for lambda phage. They tracked the dynamics of three key genes cro, cI and cII and their protein production. The decision circuit involved both negative and positive feedback loops, which responded differently to changes in the total number of viral genomes inside a cell. The positive feedback loop was lin
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Georgia Institute of Technology Research News