Though current vaccines reduce the impact of influenza, IAV remains a major human pathogen with an enormous global and domestic impact, causing 30,000 deaths and economic costs totaling tens of billions dollars each year in the USA. Despite its remarkable impact on public health, we have only a limited understanding of the molecular mechanisms underlying viral pathogenesis and its ability to evade the immune response. In this project we are studying a number of aspects of the interaction between IAV and the host. Most of studies utilize the mouse model of infection. Our interests include understanding selection of antigenic variants in vivo, the interaction between the nervous and immune systems in regulating anti-viral immunity, and the role of the PB1-F2 protein in viral pathogenesis. We found that PB1-F2 enhances influenza A virus pathology as well as the additional pathology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI001014-02
Application #
7732664
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2008
Total Cost
$384,203
Indirect Cost
City
State
Country
United States
Zip Code
Hensley, Scott E; Das, Suman R; Bailey, Adam L et al. (2009) Hemagglutinin receptor binding avidity drives influenza A virus antigenic drift. Science 326:734-6
Haeryfar, S M Mansour; Hickman, Heather D; Irvine, Kari R et al. (2008) Terminal deoxynucleotidyl transferase establishes and broadens antiviral CD8+ T cell immunodominance hierarchies. J Immunol 181:649-59
Grebe, Kristie M; Yewdell, Jonathan W; Bennink, Jack R (2008) Heterosubtypic immunity to influenza A virus: where do we stand? Microbes Infect 10:1024-9
Holmes, Edward C; Lipman, David J; Zamarin, Dmitriy et al. (2006) Comment on ""Large-scale sequence analysis of avian influenza isolates"". Science 313:1573; author reply 1573