Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI001055-06
Application #
8745490
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2013
Total Cost
$375,747
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

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; 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
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
Graber, Tyson E; Hébert-Seropian, Sarah; Khoutorsky, Arkady et al. (2013) Reactivation of stalled polyribosomes in synaptic plasticity. Proc Natl Acad Sci U S A 110:16205-10
Yewdell, Jonathan W (2013) To dream the impossible dream: universal influenza vaccination. Curr Opin Virol 3:316-21
Ince, William L; Gueye-Mbaye, Aissatou; Bennink, Jack R et al. (2013) Reassortment complements spontaneous mutation in influenza A virus NP and M1 genes to accelerate adaptation to a new host. J Virol 87:4330-8
Brooke, Christopher B; Yewdell, Jonathan W (2013) Host versus flu: antibodies win a round? Nat Struct Mol Biol 20:245-6

Showing the most recent 10 out of 23 publications