Despite its enormous impact on public health, we have only a limited understanding of the molecular mechanisms underlying influenza A virus (IAV) ability to evade the immune response. Antigenic drift precludes long lasting natural or vaccine induced immunity, and is the cause of yearly vaccine reformulation. Despite its importance, we have only a limited understanding of the molecular mechanisms underlying antigenic drift of IAV and the fine specificity of the B cell response to the IAV hemagglutinin. We are examining the changes in the structure and function of the influenza HA that provide an advantage in the face of the host neutralizing antibody response. This year we have been examining the role of non-infectious/semi-infectious virions during virus infection. Our studies suggest that the traditional propagation dependent assays of infectivity underestimate the true infectious potential of a virus population.

Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2013
Total Cost
$375,747
Indirect Cost
City
State
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Zip Code
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
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:
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
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
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
Yu, Cheng-Rong; Dambuza, Ivy M; Lee, Yong-Jun et al. (2013) STAT3 regulates proliferation and survival of CD8+ T cells: enhances effector responses to HSV-1 infection, and inhibits IL-10+ regulatory CD8+ T cells in autoimmune uveitis. Mediators Inflamm 2013:359674
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
Brooke, Christopher B; Ince, William L; Wrammert, Jens et al. (2013) Most influenza a virions fail to express at least one essential viral protein. J Virol 87:3155-62
Yewdell, Jonathan W; Ince, William L (2013) Greasing the SCIDs for Universal Flu Antibodies. Cell Host Microbe 14:7-8

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