Effect of 1918 PB1-F2 expression on influenza a virus infection kinetics

Amber M. Smith, Frederick R. Adler, Julie L. McAuley, Ryan N Gutenkunst, Ruy M. Ribeiro, Jonathan A. McCullers, Alan S. Perelson

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Relatively little is known about the viral factors contributing to the lethality of the 1918 pandemic, although its unparalleled virulence was likely due in part to the newly discovered PB1-F2 protein. This protein, while unnecessary for replication, increases apoptosis in monocytes, alters viral polymerase activity in vitro, enhances inflammation and increases secondary pneumonia in vivo. However, the effects the PB1-F2 protein have in vivo remain unclear. To address the mechanisms involved, we intranasally infected groups of mice with either influenza A virus PR8 or a genetically engineered virus that expresses the 1918 PB1-F2 protein on a PR8 background, PR8-PB1-F2(1918). Mice inoculated with PR8 had viral concentrations peaking at 72 hours, while those infected with PR8-PB1-F2(1918) reached peak concentrations earlier, 48 hours. Mice given PR8-PB1-F2(1918) also showed a faster decline in viral loads. We fit a mathematical model to these data to estimate parameter values. The model supports a higher viral production rate per cell and a higher infected cell death rate with the PR8-PB1-F2(1918) virus. We discuss the implications these mechanisms have during an infection with a virus expressing a virulent PB1-F2 on the possibility of a pandemic and on the importance of antiviral treatments.

Original languageEnglish (US)
Article numbere1001081
JournalPLoS Computational Biology
Volume7
Issue number2
DOIs
StatePublished - Feb 2011

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influenza
Influenza
Virus Diseases
Orthomyxoviridae
Viruses
Virus
Infection
virus
Kinetics
Proteins
Protein
kinetics
Mouse
protein
Pandemics
pandemic
Cell death
infection
viruses
mice

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Ecology
  • Molecular Biology
  • Genetics
  • Ecology, Evolution, Behavior and Systematics
  • Modeling and Simulation
  • Computational Theory and Mathematics

Cite this

Smith, A. M., Adler, F. R., McAuley, J. L., Gutenkunst, R. N., Ribeiro, R. M., McCullers, J. A., & Perelson, A. S. (2011). Effect of 1918 PB1-F2 expression on influenza a virus infection kinetics. PLoS Computational Biology, 7(2), [e1001081]. https://doi.org/10.1371/journal.pcbi.1001081

Effect of 1918 PB1-F2 expression on influenza a virus infection kinetics. / Smith, Amber M.; Adler, Frederick R.; McAuley, Julie L.; Gutenkunst, Ryan N; Ribeiro, Ruy M.; McCullers, Jonathan A.; Perelson, Alan S.

In: PLoS Computational Biology, Vol. 7, No. 2, e1001081, 02.2011.

Research output: Contribution to journalArticle

Smith, AM, Adler, FR, McAuley, JL, Gutenkunst, RN, Ribeiro, RM, McCullers, JA & Perelson, AS 2011, 'Effect of 1918 PB1-F2 expression on influenza a virus infection kinetics', PLoS Computational Biology, vol. 7, no. 2, e1001081. https://doi.org/10.1371/journal.pcbi.1001081
Smith, Amber M. ; Adler, Frederick R. ; McAuley, Julie L. ; Gutenkunst, Ryan N ; Ribeiro, Ruy M. ; McCullers, Jonathan A. ; Perelson, Alan S. / Effect of 1918 PB1-F2 expression on influenza a virus infection kinetics. In: PLoS Computational Biology. 2011 ; Vol. 7, No. 2.
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