Details:

Alternative Title:
PLoS Comput Biol
Publisher's site:
http://dx.doi.org/10.1371/journal.pcbi.1002746
Personal Author:
Birch, Elsa W. ; Ruggero, Nicholas A. ; Covert, Markus W. ;
Birch, Elsa W. ; Ruggero, Nicholas A. ; Covert, Markus W. ; Less -
Description:
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 specification of host nutritional environment, and predictions compare favorably to experimental measurements of phage replication in multiple environments. The level of detail of our computational predictions facilitates exploration of the dynamic changes in host metabolic fluxes that result from viral resource consumption, as well as analysis of the limiting processes dictating maximum viral progeny production. For example, although it is commonly assumed that viral infection dynamics are predominantly limited by the amount of protein synthesis machinery in the host, our results suggest that in many cases metabolic limitation is at least as strict. Taken together, these results emphasize the importance of considering viral infections in the context of host metabolism.
Subject:
[+]
Algorithms
Bacteriophage T7
Biology
Computer Simulation
Culture Media
Escherichia Coli
Host-Pathogen Interactions
Metabolic Networks And Pathways
Models, Biological
Reproducibility Of Results
Research Article
Systems Biology
Virus Replication

Source:
PLoS Comput Biol. 2012 ; 8(10).;
Pubmed ID:
23093930
Pubmed Central ID:
PMC3475664
Document Type:
Journal Article ;
Funding:
5DP1LM01150-05/DP/NCCDPHP CDC HHS/United States ; DP1 LM011510/LM/NLM NIH HHS/United States ;
5DP1LM01150-05/DP/NCCDPHP CDC HHS/United States ; DP1 LM011510/LM/NLM NIH HHS/United States ; Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:47b9fea53925538d9202496fb3852f4c782874b1b2043c452cb88a748585b5fc
File Type:

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