Determining host metabolic limitations on viral replication via integrated modeling and experimental perturbation.

ABSTRACT: Viral replication relies on host metabolic machinery and precursors to produce large numbers of progeny - often very rapidly. A fundamental example is the infection of Escherichia coli by bacteriophage T7. The resource draw imposed by viral replication represents a significant and complex perturbation to the extensive and interconnected network of host metabolic pathways. To better understand this system, we have integrated a set of structured ordinary differential equations quantifying T7 replication and an E. coli flux balance analysis metabolic model. Further, we present here an integrated simulation algorithm enforcing mutual constraint by the models across the entire duration of phage replication. This method enables quantitative dynamic prediction of virion production given only spec

SUBMITTER: Birch EW 

PROVIDER: S-EPMC3475664 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature