Higher level of replication efficiency of 2009 (H1N1) pandemic influenza virus than those of seasonal and avian strains: Kinetics from epithelial cell culture and computational modeling

Hugh Mitchell, Drew Levin, Stephanie Forrest, Catherine A.A. Beauchemin, Jennifer Tipper, Jennifer Knight, Nathaniel Donart, R. Colby Layton, John Pyles, Peng Gao, Kevin S. Harrod, Alan S. Perelson, Frederick Koster

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

The pathogenicity and transmission of influenza A viruses are likely determined in part by replication efficiency in human cells, which is the net effect of complex virus-host interactions. H5N1 avian, H1N1 seasonal, and H1N1 2009 pandemic influenza virus strains were compared by infecting human differentiated bronchial epithelial cells in air-liquid interface cultures at relatively low virus particle/cell ratios. Differential equation and computational models were used to characterize the in vitro kinetic behaviors of the three strains. The models were calibrated by fitting experimental data in order to estimate difficult-to-measure parameters. Both models found marked differences in the relative values of p, the virion production rate per cell, and R0, an index of the spread of infection through the monolayer, with the values for the strains in the following rank order (from greatest to least): pandemic strain, followed by seasonal strain, followed by avian strain, as expected. In the differential equation model, which treats virus and cell populations as well mixed, R0 and p varied proportionately for all 3 strains, consistent with a primary role for productivity. In the spatially explicit computational model, R0 and p also varied proportionately except that R0 derived for the pandemic strain was reduced, consistent with constrained viral spread imposed by multiple host defenses, including mucus and paracrine antiviral effects. This synergistic experimental-computational strategy provides relevant parameters for identifying and phenotyping potential pandemic strains.

Original languageEnglish (US)
Pages (from-to)1125-1135
Number of pages11
JournalJournal of virology
Volume85
Issue number2
DOIs
StatePublished - Jan 2011

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Mitchell, H., Levin, D., Forrest, S., Beauchemin, C. A. A., Tipper, J., Knight, J., Donart, N., Colby Layton, R., Pyles, J., Gao, P., Harrod, K. S., Perelson, A. S., & Koster, F. (2011). Higher level of replication efficiency of 2009 (H1N1) pandemic influenza virus than those of seasonal and avian strains: Kinetics from epithelial cell culture and computational modeling. Journal of virology, 85(2), 1125-1135. https://doi.org/10.1128/JVI.01722-10