Influenza A viruses (IAVs) cause seasonal outbreaks and occasional severe pandemics that are a significant burden in morbidity, mortality, and economic loss. The continuous evolution of IAV through mutation and reassortment provide molecular mechanisms to allow IAV to evade host immunity. However, there remain significant gaps in our understanding of the tug of war between host and virus, particularly, the molecular mechanisms influenza virus employs through evolution in response to host defenses and the implications this may have for vaccination strategies. In 2018, by focusing on the biology, evolution and pathogenesis of the virus, we have aimed to determine first the significance and extent of IAV evolution caused by acute primary and memory (vaccination) adaptive immune responses. Specifically, we are utilizing next generation sequencing of the full Influenza virus genome to determine the kinetics and extent of virus evolution. We are determining whether our current vaccination strategies result in enhanced viral evolution and whether the viral evolution rate could be used as an early indicator of vaccine efficacy. Second, we want to elucidate the role of Influenza virus protein evolution in viral pathogenesis and transmission. Through these studies, we aim to further our understanding of IAV evolution and the underlying causative host mechanisms. It is hoped that with a better understanding of the highly adaptive IAV, these studies will uncover novel and improved ways to vaccinate and combat IAV infection.

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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
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
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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