IJPAM: Volume 89, No. 2 (2013)


Tori Huffman$^1$, Kathryn Link$^2$, John Nardini$^3$, Laura Poag$^4$,
Kevin Flores$^5$, H.T. Banks$^6$,
Bernat Blasco$^7$, Jennifer Jungfleisch$^8$, Juana Diez$^9$
$^{1,2,3,4,5,6}$Center for Research in Scientific Computation
North Carolina State University
Raleigh, NC, USA
$^{7,8,9}$Molecular Virology Group
Department of Experimental and Health Sciences
Univesitat Pompeu Fabra, PRBB
08003 Barcelona, SPAIN

Abstract. Positive-strand RNA viruses, such as the brome mosaic virus (BMV) and hepatitis C virus, utilize a replication cycle which involves the recruitment of RNA genomes from the cellular translation machinery to the viral replication complexes. Here, we coupled mathematical modeling with a statistical inverse problem methodology to better understand this crucial recruitment process. We developed a discrete-delay differential equation model that describes the production of BMV protein 1a and BMV RNA3, and the effect of protein 1a on RNA3 recruitment. We validated our model with experimental data generated in duplicate from a yeast strain that was engineered to express protein 1a and RNA3 under the control of inducible promoters. We used a statistical model comparison technique to test which biological assumptions in our model were correct. Our results suggest that protein 1a expression is governed by a nonlinear phenomenon and that a time delay is important for modeling RNA3 recruitment. We also performed an uncertainty analysis of two experimental designs and found that we could improve our data collection procedure in future experiments to increase the confidence in our parameter estimates.

Received: September 20, 2013

AMS Subject Classification:

Key Words and Phrases: positive-strand RNA virus, brome mosaic virus, Saccharomyces cerevisiae, inverse problem, uncertainty analysis, time delay

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DOI: 10.12732/ijpam.v89i2.9 How to cite this paper?
International Journal of Pure and Applied Mathematics
ISSN printed version: 1311-8080
ISSN on-line version: 1314-3395
Year: 2013
Volume: 89
Issue: 2