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Virology. 2011 Aug 15;417(1):27-36. doi: 10.1016/j.virol.2011.04.020. Epub 2011 May 25.

Virus infection rapidly activates the P58(IPK) pathway, delaying peak kinase activation to enhance viral replication.

Author information

1
Department of Cellular and Molecular Biology, Centro Nacional de Biotecnología, CSIC, Madrid, Spain. agoodman@med.miami.edu

Abstract

Previously we showed that the cellular protein P58(IPK) contributes to viral protein synthesis by decreasing the activity of the anti-viral protein, PKR. Here, we constructed a mathematical model to examine the P58(IPK) pathway and investigated temporal behavior of this biological system. We find that influenza virus infection results in the rapid activation of P58(IPK) which delays and reduces maximal PKR and eIF2α phosphorylation, leading to increased viral protein levels. We confirmed that the model could accurately predict viral and host protein levels at extended time points by testing it against experimental data. Sensitivity analysis of relative reaction rates describing P58(IPK) activity and the downstream proteins through which it functions helped identify processes that may be the most beneficial targets to thwart virus replication. Together, our study demonstrates how computational modeling can guide experimental design to further understand a specific metabolic signaling pathway during viral infection in a mammalian system.

PMID:
21612809
PMCID:
PMC3152592
DOI:
10.1016/j.virol.2011.04.020
[Indexed for MEDLINE]
Free PMC Article

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