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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AI049178-02
Application #
6511458
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Klein, David L
Project Start
2001-04-01
Project End
2004-03-31
Budget Start
2002-04-01
Budget End
2003-03-31
Support Year
2
Fiscal Year
2002
Total Cost
$118,150
Indirect Cost
Name
St. Jude Children's Research Hospital
Department
Type
DUNS #
067717892
City
Memphis
State
TN
Country
United States
Zip Code
38105
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Peltola, Ville T; Boyd, Kelli L; McAuley, Julie L et al. (2006) Bacterial sinusitis and otitis media following influenza virus infection in ferrets. Infect Immun 74:2562-7
McCullers, Jonathan A (2006) Insights into the interaction between influenza virus and pneumococcus. Clin Microbiol Rev 19:571-82
Peltola, Ville T; Murti, K Gopal; McCullers, Jonathan A (2005) Influenza virus neuraminidase contributes to secondary bacterial pneumonia. J Infect Dis 192:249-57
McCullers, Jonathan A (2004) Effect of antiviral treatment on the outcome of secondary bacterial pneumonia after influenza. J Infect Dis 190:519-26
Peltola, Ville T; McCullers, Jonathan A (2004) Respiratory viruses predisposing to bacterial infections: role of neuraminidase. Pediatr Infect Dis J 23:S87-97
McCullers, Jonathan A; Bartmess, Kimberly C (2003) Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumoniae. J Infect Dis 187:1000-9
McCullers, Jonathan A; Rehg, Jerold E (2002) Lethal synergism between influenza virus and Streptococcus pneumoniae: characterization of a mouse model and the role of platelet-activating factor receptor. J Infect Dis 186:341-50