Kinetics of coinfection with influenza A virus and Streptococcus pneumoniae
Amber M Smith1, Frederick R Adler, Ruy M Ribeiro
1Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America. amber.smith@stjude.org
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.
Insights
Secondary bacterial infections, like Streptococcus pneumoniae, worsen influenza outcomes. Viral titers rebound during bacterial coinfection, driven by bacterial dose, not viral strain, impacting disease dynamics.
Area of Science:
- Virology
- Immunology
- Microbiology
Background:
- Secondary bacterial infections significantly increase influenza morbidity and mortality.
- Lethal synergism between influenza viruses and bacteria, especially Streptococcus pneumoniae, is observed, but mechanisms remain unclear.
Purpose of the Study:
- To elucidate the mechanisms underlying influenza and Streptococcus pneumoniae coinfections.
- To determine the influence of pathogen dose and strain on disease dynamics.
Main Methods:
- Mice were infected with influenza A virus (H1N1 subtype) or a variant expressing the 1918 PB1-F2 protein.
- Mice were subsequently infected with one of two Streptococcus pneumoniae strains (type 2 or type 3).
- Viral and bacterial titers were monitored, and a kinetic model was employed to analyze pathogen interactions.
Main Results:
- Following bacterial infection, viral titers showed an initial rebound followed by a slow decline.
- Bacterial titers rapidly increased to high levels and remained elevated.
- Disease dynamics were influenced by the initial bacterial dose but not by the expression of the 1918 PB1-F2 protein.
Conclusions:
- Hypothesized mechanisms include enhanced viral release and impaired alveolar macrophage function during coinfection.
- The study provides a kinetic modeling framework for investigating pathogen interactions in coinfections.
- Findings highlight the impact of bacterial inoculum size on influenza-bacterial coinfection dynamics.
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