title: Kinetics of coinfection with influenza A virus and Streptococcus pneumoniae.
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.
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America. amber.smith@stjude.org
authors.forename: Amber M
authors.initials: AM
authors.lastname: Smith
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Adler
authors.forename: Ruy M
authors.initials: RM
authors.lastname: Ribeiro
authors.forename: Ryan N
authors.initials: RN
authors.lastname: Gutenkunst
authors.forename: Julie L
authors.initials: JL
authors.lastname: McAuley
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: McCullers
authors.forename: Alan S
authors.initials: AS
authors.lastname: Perelson
mesh_terms: D000818:Animals; D060085:Coinfection / Q000382:microbiology / Q000503:physiopathology / Q000821:virology; D005260:Female; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000472:pathogenicity; D007700:Kinetics; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008962:Models, Theoretical; D009976:Orthomyxoviridae Infections / Q000150:complications* / Q000276:immunology; D011008:Pneumococcal Infections / Q000150:complications* / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000472:pathogenicity; D013997:Time Factors
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