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Model-based simulation and prediction of an antiviral strategy against influenza A infection.

Title
Model-based simulation and prediction of an antiviral strategy against influenza A infection.
Authors
Kye- Yeon HurMoon, JYSeung-Hwan KimYoo, JY
POSTECH Authors
Yoo, JY
Date Issued
Jul-2013
Publisher
San Francisco, CA : Public Library of Science
Abstract
There is a strong need to develop novel strategies in using antiviral agents to efficiently treat influenza infections. Thus, we constructed a rule-based mathematical model that reflects the complicated interactions of the host immunity and viral life cycle and analyzed the key controlling steps of influenza infections. The main characteristics of the pandemic and seasonal influenza strains were estimated using parameter values derived from cells infected with Influenza A/California/04/2009 and Influenza A/NewCaledonia/20/99, respectively. The quantitative dynamics of the infected host cells revealed a more aggressive progression of the pandemic strain than the seasonal strain. The perturbation of each parameter in the model was then tested for its effects on viral production. In both the seasonal and pandemic strains, the inhibition of the viral release (k(C)), the reinforcement of viral attachment (k(V)), and an increased transition rate of infected cells into activated cells (k(I)) exhibited significant suppression effects on the viral production
however, these inhibitory effects were only observed when the numerical perturbations were performed at the early stages of the infection. In contrast, combinatorial perturbations of both the inhibition of viral release and either the reinforcement of the activation of infected cells or the viral attachment exhibited a significant reduction in the viral production even at a later stage of infection. These results suggest that, in addition to blocking the viral release, a combination therapy that also enhances either the viral attachment or the transition of the infected cells might provide an alternative for effectively controlling progressed influenza infection.
Keywords
OSELTAMIVIR-RESISTANT; VIRUS-INFECTION; CELL-CULTURE; NEURAMINIDASE INHIBITORS; ENCEPHALITIS-VIRUS; RECEPTOR-BINDING; DENDRITIC CELLS; HOST-DEFENSE; MDCK CELLS; MICE
URI
http://oasis.postech.ac.kr/handle/2014.oak/12682
DOI
10.1371/JOURNAL.PONE.0068235
ISSN
1932-6203
Article Type
Article
Citation
PLoS One, vol. 8, no. 7, page. E68235 - E68235, 2013-07
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유주연YOO, JOO YEON
Dept of Life Sciences
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