Lethal synergism between influenza and pneumococcus

Summary

Principal Investigator: J A McCullers
Abstract: The K08 Award will provide an opportunity for the applicant to extend his virology training in the area of viral-bacterial interactions and to develop new expertise in pneumococcal pathogenesis in the setting of prior viral infection. These skills will enable the applicant to achieve his long term career goals by becoming a fully independent research scientist who can translate observations made at the bench into therapeutics and interventions at the bedside. Epidemiologic evidence suggests that there is a lethal synergism between influenza A virus and Streptococcus pneumonias accounting for excess mortality (average 20,000 influenza-related deaths per year in the US) during influenza epidemics. However, the pathogenic mechanisms underlying this interaction are poorly understood, and the lack of a suitable animal model of pneumonia following infection with both organisms has hampered study. The goal of the proposed research plan is to determine the role of receptor alterations engendered by influenza virus infection in the pathogenesis of pneumococcal pneumonia. A newly developed murine model of dual infection will be used to examine the relationships of timing and of infectious doses of influenza virus and pneumococcus to morbidity and mortality. Influenza viruses with different pathogenic features in the mouse will be utilized to determine how cytokine expression varies with different viruses. Expression of receptors permissive for pneumococcal adherence and invasion will be examined in the context of cytokine expression following influenza virus infection, and a correlation to development of pneumonia and in the murine model of dual infection will be made. Identification of specific pneumococcal proteins involved in this synergistic interaction will provide drug and vaccine targets for future intervention in human disease and death caused by pneumococcal superinfection following influenza.
Funding Period: 2001-04-01 - 2004-03-31
more information: NIH RePORT

Top Publications

  1. pmc Influenza virus neuraminidase contributes to secondary bacterial pneumonia
    Ville T Peltola
    Department of Infectious Diseases, St Jude Children s Research Hospital, Memphis, Tennessee 38105 2794, USA
    J Infect Dis 192:249-57. 2005
  2. pmc Bacterial sinusitis and otitis media following influenza virus infection in ferrets
    Ville T Peltola
    Department of Infectious Diseases, St Jude Children s Research Hospital, 332 N Lauderdale St, Memphis, TN 38105 2794, USA
    Infect Immun 74:2562-7. 2006
  3. pmc Insights into the interaction between influenza virus and pneumococcus
    Jonathan A McCullers
    Department of Infectious Diseases, St Jude Children s Research Hospital, 332 N Lauderdale St, Memphis, TN 38105 2794, USA
    Clin Microbiol Rev 19:571-82. 2006
  4. pmc Induction of pro- and anti-inflammatory molecules in a mouse model of pneumococcal pneumonia after influenza
    Matthew W Smith
    Department of Infectious Diseases, St Jude Children s Research Hospital, Memphis, TN, USA
    Comp Med 57:82-9. 2007

Scientific Experts

  • J A McCullers
  • Ville T Peltola
  • Matthew W Smith
  • Jerold E Rehg
  • Jeffrey E Schmidt
  • Carlos J Orihuela
  • Kelli L Boyd
  • Julie L McAuley
  • K Gopal Murti

Detail Information

Publications4

  1. pmc Influenza virus neuraminidase contributes to secondary bacterial pneumonia
    Ville T Peltola
    Department of Infectious Diseases, St Jude Children s Research Hospital, Memphis, Tennessee 38105 2794, USA
    J Infect Dis 192:249-57. 2005
    ..These data lend support to our hypothesis that the influenza virus neuraminidase contributes to secondary bacterial pneumonia and subsequent excess mortality...
  2. pmc Bacterial sinusitis and otitis media following influenza virus infection in ferrets
    Ville T Peltola
    Department of Infectious Diseases, St Jude Children s Research Hospital, 332 N Lauderdale St, Memphis, TN 38105 2794, USA
    Infect Immun 74:2562-7. 2006
    ..These data may partially explain why bacterial complication rates are higher during seasons when H3N2 viruses predominate. This animal model will be useful for further study of the mechanisms that underlie viral-bacterial synergism...
  3. pmc Insights into the interaction between influenza virus and pneumococcus
    Jonathan A McCullers
    Department of Infectious Diseases, St Jude Children s Research Hospital, 332 N Lauderdale St, Memphis, TN 38105 2794, USA
    Clin Microbiol Rev 19:571-82. 2006
    ..Identification and exploration of the underlying mechanisms responsible for this synergism will provide targets for prevention and treatment using drugs and vaccines...
  4. pmc Induction of pro- and anti-inflammatory molecules in a mouse model of pneumococcal pneumonia after influenza
    Matthew W Smith
    Department of Infectious Diseases, St Jude Children s Research Hospital, Memphis, TN, USA
    Comp Med 57:82-9. 2007
    ..Mortality correlated with the development of pneumonia and lung inflammation but not with bacteremia. This model has the potential to help us understand the pathogenesis of severe lung infections...