With a single virus, cro dominated and the lytic pathway prevailed. If the number of co-infecting viruses exceeded a certain threshold, the positive feedback loop associated with cI dominated, turning the switch to the lysogenic pathway. The differences in bacterial cell fate were stark and hinged upon whether or not one or two viruses were inside a given cell.
The researchers found that the cII gene acted as the gate for the system. Increasing the number of viruses drove the dynamic level of cII proteins past a critical point facilitating production of cI proteins leading to the lysogenic pathway.
"The decision circuit is a race between two pathways and in the case of a single virus, the outcome is biased toward lysis," explained Weitz. "In our model, when multiple viruses infect a given cell, the overall production of regulatory proteins increases. This transient increase is reinforced by a positive feedback loop in the latency pathway, permitting even higher production of lysogenic proteins, and ultimately the latent outcome."
The central idea in the model proposed by Weitz and collaborators is that increases in the overall amount of viral proteins produced from multiple viral genomes can have a dramatic effect on the nonlinear gene networks that control cell fate.
"Many questions still remain, including to what extent subsequent viruses can change the outcome of previously infected, but not yet committed, viruses, and to what extent microenvironments inside the host impact cell fate," added Weitz. "Nonetheless, this study proposes a mechanistic explanation to a long-standing paradox by showing that when multiple viruses infect a host cell, those viruses can make a collective decision rather than behaving as they would individually."
|Contact: Abby Vogel|
Georgia Institute of Technology Research News