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Journal of Virology, August 2006, p. 7590-7599, Vol. 80, No. 15
0022-538X/06/$08.00+0     doi:10.1128/JVI.01623-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Kinetics of Influenza A Virus Infection in Humans

Prasith Baccam,1,{dagger} Catherine Beauchemin,2 Catherine A. Macken,1 Frederick G. Hayden,3 and Alan S. Perelson1*

Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico 87545,1 Department of Physics, University of Alberta, Edmonton, Alberta, T6G 2J1, Canada,2 Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville, Virginia 229083

Received 2 August 2005/ Accepted 5 May 2006

Currently, little is known about the viral kinetics of influenza A during infection within an individual. We utilize a series of mathematical models of increasing complexity, which incorporate target cell limitation and the innate interferon response, to examine influenza A virus kinetics in the upper respiratory tracts of experimentally infected adults. The models were fit to data from an experimental H1N1 influenza A/Hong Kong/123/77 infection and suggest that it is important to include the eclipse phase of the viral life cycle in viral dynamic models. Doing so, we estimate that after a delay of ~6 h, infected cells begin producing influenza virus and continue to do so for ~5 h. The average lifetime of infected cells is ~11 h, and the half-life of free infectious virus is ~3 h. We calculated the basic reproductive number, R0, which indicated that a single infected cell could produce ~22 new productive infections. This suggests that antiviral treatments have a large hurdle to overcome in moderating symptoms and limiting infectiousness and that treatment has to be initiated as early as possible. For about 50% of patients, the curve of viral titer versus time has two peaks. This bimodal behavior can be explained by incorporating the antiviral effects of interferon into the model. Our model also compared well to an additional data set on viral titer after experimental infection and treatment with the neuraminidase inhibitor zanamivir, which suggests that such models may prove useful in estimating the efficacies of different antiviral therapies for influenza A infection.

* Corresponding author. Mailing address: MS-K710, Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545. Phone: (505) 667-6829. Fax: (505) 665-3493. E-mail: asp{at}lanl.gov.

{dagger} Present address: Innovative Emergency Management, Inc., Bel Air, MD 21015.

Journal of Virology, August 2006, p. 7590-7599, Vol. 80, No. 15
0022-538X/06/$08.00+0     doi:10.1128/JVI.01623-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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