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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. In this paper, 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. Finally, our model provides a framework to investigate pathogen interaction during coinfections and to uncovermore » dynamical differences based on inoculum size and strain.« less

Authors:
 [1];  [2];  [3];  [4];  [5];  [1];  [6]
  1. St. Jude Children's Research Hospital, Memphis, TN (United States). Dept. of Infectious Diseases
  2. Univ. of Utah, Salt Lake City, UT (United States). Dept. of Mathematics. Dept. of Biology
  3. Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Biology and Biophysics; Univ. of Lisbon (Portugal). School of Medicine. Inst. of Molecular Medicine
  4. Univ. of Arizona, Tucson, AZ (United States). Dept. of Molecular and Cellular Biology
  5. Univ. of Melbourne (Australia). Dept. of Immunology and Microbiology
  6. Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Biology and Biophysics
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE; National Inst. of Health (NIH) (United States); National Science Foundation (NSF); James S. McDonnell Foundation (United States); Foundation for Science and Technology (FCT) (Portugal)
Contributing Org.:
St. Jude Children's Research Hospital, Memphis, TN (United States); Univ. of Utah, Salt Lake City, UT (United States); Univ. of Arizona, Tucson, AZ (United States); Univ. of Melbourne (Australia)
OSTI Identifier:
1321716
Report Number(s):
LA-UR-12-21471
Journal ID: ISSN 1553-7374
Grant/Contract Number:  
AC52-06NA25396; HHSN272201000055C; OD011095; AI028433; AI100946; P20-GM103452; DMS-0354259; PCOFUND-GA-2009-246542
Resource Type:
Accepted Manuscript
Journal Name:
PLoS Pathogens
Additional Journal Information:
Journal Volume: 9; Journal Issue: 3; Journal ID: ISSN 1553-7374
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; biological science; influenza; co-infections; pneumococcus; alveolar macrophages; bacterial diseases; influenza A virus; influenza viruses; bacterial pathogens

Citation Formats

Smith, Amber M., Adler, Frederick R., Ribeiro, Ruy M., Gutenkunst, Ryan N., McAuley, Julie L., McCullers, Jonathan A., and Perelson, Alan S. Kinetics of Coinfection with Influenza A Virus and Streptococcus pneumoniae. United States: N. p., 2013. Web. doi:10.1371/journal.ppat.1003238.
Smith, Amber M., Adler, Frederick R., Ribeiro, Ruy M., Gutenkunst, Ryan N., McAuley, Julie L., McCullers, Jonathan A., & Perelson, Alan S. Kinetics of Coinfection with Influenza A Virus and Streptococcus pneumoniae. United States. https://doi.org/10.1371/journal.ppat.1003238
Smith, Amber M., Adler, Frederick R., Ribeiro, Ruy M., Gutenkunst, Ryan N., McAuley, Julie L., McCullers, Jonathan A., and Perelson, Alan S. Thu . "Kinetics of Coinfection with Influenza A Virus and Streptococcus pneumoniae". United States. https://doi.org/10.1371/journal.ppat.1003238. https://www.osti.gov/servlets/purl/1321716.
@article{osti_1321716,
title = {Kinetics of Coinfection with Influenza A Virus and Streptococcus pneumoniae},
author = {Smith, Amber M. and Adler, Frederick R. and Ribeiro, Ruy M. and Gutenkunst, Ryan N. and McAuley, Julie L. and McCullers, Jonathan A. and Perelson, Alan S.},
abstractNote = {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. In this paper, 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. Finally, our model provides a framework to investigate pathogen interaction during coinfections and to uncover dynamical differences based on inoculum size and strain.},
doi = {10.1371/journal.ppat.1003238},
journal = {PLoS Pathogens},
number = 3,
volume = 9,
place = {United States},
year = {2013},
month = {3}
}

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