Kinetics of Coinfection with Influenza A Virus and Streptococcus pneumoniae

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

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Secondary bacterial infections are a leading cause of illness and death during epidemic and pandemic influenza. Experimental studies suggest a lethal synergism between influenza and certain bacteria, particularly Streptococcus pneumoniae, but the precise processes involved are unclear. To address the mechanisms and determine the influences of pathogen dose and strain on disease, we infected groups of mice with either the H1N1 subtype influenza A virus A/Puerto Rico/8/34 (PR8) or a version expressing the 1918 PB1-F2 protein (PR8-PB1-F2(1918)), followed seven days later with one of two S. pneumoniae strains, type 2 D39 or type 3 A66.1. We determined that, following bacterial infection, viral titers initially rebound and then decline slowly. Bacterial titers rapidly rise to high levels and remain elevated. We used a kinetic model to explore the coupled interactions and study the dominant controlling mechanisms. We hypothesize that viral titers rebound in the presence of bacteria due to enhanced viral release from infected cells, and that bacterial titers increase due to alveolar macrophage impairment. Dynamics are affected by initial bacterial dose but not by the expression of the influenza 1918 PB1-F2 protein. Our model provides a framework to investigate pathogen interaction during coinfections and to uncover dynamical differences based on inoculum size and strain.

Original languageEnglish (US)
Article numbere1003238
JournalPLoS Pathogens
Volume9
Issue number3
DOIs
StatePublished - Apr 15 2013

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Influenza A virus
Streptococcus pneumoniae
Coinfection
Human Influenza
Puerto Rico
Bacterial Infections
Bacteria
H1N1 Subtype Influenza A Virus
Alveolar Macrophages
Pandemics
Cause of Death
Proteins

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Smith, A., Adler, F. R., Ribeiro, R. M., Gutenkunst, R. N., McAuley, J. L., Mccullers, J., & Perelson, A. S. (2013). Kinetics of Coinfection with Influenza A Virus and Streptococcus pneumoniae. PLoS Pathogens, 9(3), [e1003238]. https://doi.org/10.1371/journal.ppat.1003238

Kinetics of Coinfection with Influenza A Virus and Streptococcus pneumoniae. / Smith, Amber; Adler, Frederick R.; Ribeiro, Ruy M.; Gutenkunst, Ryan N.; McAuley, Julie L.; Mccullers, Jonathan; Perelson, Alan S.

In: PLoS Pathogens, Vol. 9, No. 3, e1003238, 15.04.2013.

Research output: Contribution to journalArticle

Smith, A, Adler, FR, Ribeiro, RM, Gutenkunst, RN, McAuley, JL, Mccullers, J & Perelson, AS 2013, 'Kinetics of Coinfection with Influenza A Virus and Streptococcus pneumoniae', PLoS Pathogens, vol. 9, no. 3, e1003238. https://doi.org/10.1371/journal.ppat.1003238
Smith, Amber ; Adler, Frederick R. ; Ribeiro, Ruy M. ; Gutenkunst, Ryan N. ; McAuley, Julie L. ; Mccullers, Jonathan ; Perelson, Alan S. / Kinetics of Coinfection with Influenza A Virus and Streptococcus pneumoniae. In: PLoS Pathogens. 2013 ; Vol. 9, No. 3.
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