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, host-pathogen interactions in regulating anti-viral immunity, and the role of influenza protein in viral pathogenesis. Our current studies have been aimed at understanding the evolution of influenza virus transmissibility. Our studies in 2014 have provided insight into the biogenesis of the stem region of the influenza A virus hemagglutinin. We have also continued to study the advantages of the segmented genome in IAV evolution.

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8
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2014
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Kosik, Ivan; Yewdell, Jonathan W (2017) Influenza A virus hemagglutinin specific antibodies interfere with virion neuraminidase activity via two distinct mechanisms. Virology 500:178-183
Altman, Meghan O; Bennink, Jack R; Yewdell, Jonathan W et al. (2015) Lamprey VLRB response to influenza virus supports universal rules of immunogenicity and antigenicity. Elife 4:
Frank, Gregory M; Angeletti, Davide; Ince, William L et al. (2015) A Simple Flow-Cytometric Method Measuring B Cell Surface Immunoglobulin Avidity Enables Characterization of Affinity Maturation to Influenza A Virus. MBio 6:e01156
Brooke, Christopher B; Ince, William L; Wei, Jiajie et al. (2014) Influenza A virus nucleoprotein selectively decreases neuraminidase gene-segment packaging while enhancing viral fitness and transmissibility. Proc Natl Acad Sci U S A 111:16854-9
Magadán, Javier G (2014) Zonal Sedimentation Analysis on Sucrose Gradients. Bio Protoc 4:
Magadán, Javier G; Altman, Meghan O; Ince, William L et al. (2014) Biogenesis of influenza a virus hemagglutinin cross-protective stem epitopes. PLoS Pathog 10:e1004204
Whittle, James R R; Wheatley, Adam K; Wu, Lan et al. (2014) Flow cytometry reveals that H5N1 vaccination elicits cross-reactive stem-directed antibodies from multiple Ig heavy-chain lineages. J Virol 88:4047-57
Yewdell, Jonathan W; Spiro, David J; Golding, Hana et al. (2013) Getting to the heart of influenza. Sci Transl Med 5:191ed8
Magadan, Javier G; Khurana, Surender; Das, Suman R et al. (2013) Influenza a virus hemagglutinin trimerization completes monomer folding and antigenicity. J Virol 87:9742-53
Yewdell, Jonathan W; Ince, William L (2013) Greasing the SCIDs for universal flu antibodies. Cell Host Microbe 14:7-8

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