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  Modeling the intracellular dynamics of influenza virus replication to understand the control of viral RNA synthesis

Heldt, F. S., Frensing, T., & Reichl, U. (2012). Modeling the intracellular dynamics of influenza virus replication to understand the control of viral RNA synthesis. Journal of Virology, 86(15), 7806-7817. doi:10.1128/JVI.00080-12.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0013-8A52-0 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0014-435C-9
Genre: Journal Article

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 Creators:
Heldt, Frank Stefan1, Author              
Frensing, Timo1, Author              
Reichl, Udo1, 2, Author              
Affiliations:
1Bioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, Max Planck Society, ou_1738140              
2Otto-von-Guericke-Universität Magdeburg, ou_1738156              

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Free keywords: control mechanisms, influenza A virus, mathematical modeling, viral RNA synthesis, virus replication dynamics
 Abstract: Influenza viruses transcribe and replicate their negative-sense RNA genome inside the nucleus of host cells via three viral RNA species. In the course of an infection, these RNAs show distinct dynamics, suggesting that differential regulation takes place. To investigate this regulation in a systematic way, we developed a mathematical model of influenza virus infection at the level of a single mammalian cell. It accounts for key steps of the viral life cycle, from virus entry to progeny virion release, while focusing in particular on the molecular mechanisms that control viral transcription and replication. We therefore explicitly consider the nuclear export of viral genome copies (vRNPs) and a recent hypothesis proposing that replicative intermediates (cRNA) are stabilized by the viral polymerase complex and the nucleoprotein (NP). Together, both mechanisms allow the model to capture a variety of published data sets at an unprecedented level of detail. Our findings provide theoretical support for an early regulation of replication by cRNA stabilization. However, they also suggest that the matrix protein 1 (M1) controls viral RNA levels in the late phase of infection as part of its role during the nuclear export of viral genome copies. Moreover, simulations show an accumulation of viral proteins and RNA toward the end of infection, indicating that transport processes or budding limits virion release. Thus, our mathematical model provides an ideal platform for a systematic and quantitative evaluation of influenza virus replication and its complex regulation. Copyright © 2012 by the American Society for Microbiology. [accessed November 2nd 2012]

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Language(s): eng - English
 Dates: 2012
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: eDoc: 626280
DOI: 10.1128/JVI.00080-12
Other: 34/12
 Degree: -

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Title: Journal of Virology
Source Genre: Journal
 Creator(s):
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Publ. Info: -
Pages: - Volume / Issue: 86 (15) Sequence Number: - Start / End Page: 7806 - 7817 Identifier: -