Jonathan Wilson Yewdell, M.D., Ph.D.
Cellular Biology and Viral Immunology Section
Building 33, Room 2E13C1
33 North Drive
Bethesda, MD 20892
Viruses pose a constant danger to living organisms. An astounding variety of viruses are recognized as human pathogens. The roster lengthens as humans come into more intimate contact with animal reservoirs harboring novel viruses and new technologies reveal human viruses that have previously escaped detection.
The vertebrate immune system evolved in response to the threat posed by viruses. The importance of the immune system in protecting against lethal viral infections becomes obvious in innate or acquired immunodeficiencies, where depression of one or more elements of the system results in death from a typically "self-limited" viral infection, or in the success of vaccines in preventing dangerous viral infections. The immune system (like every biological system) is not perfect, and overzealous anti-viral responses frequently contribute to viral diseases.
The mission of our laboratory is to extend basic understanding of the interaction between the immune system and viruses using mouse infection models. Ongoing projects include the following:
- Real-time imaging of virus-host interactions using multiphoton microscopy with the immediate goal of rational design of vaccines for inducing CD8+ T-cell responses
- Unraveling the role of the sympathetic nervous system in adaptive immune responses
- Understanding the generation of MHC class I peptide ligands from endogenous and exogenous viral antigens
- Defining mechanisms that contribute to antigenic drift in the influenza A virus hemagglutinin
- Understanding how PB1-F2, the 11th defined influenza A virus gene product, modulates host immunity
Brooke CB, Ince WL, Wei J, Bennink JR, Yewdell JW. Influenza A virus nucleoprotein selectively decreases neuraminidase gene-segment packaging while enhancing viral fitness and transmissibility. Proc Natl Acad Sci U S A. 2014;111(47):16854-9.
David A, Dolan BP, Hickman HD, Knowlton JJ, Clavarino G, Pierre P, Bennink JR, Yewdell JW. Nuclear translation visualized by ribosome-bound nascent chain puromycylation. J Cell Biol. 2012;197(1):45-57.
Hickman HD, Reynoso GV, Ngudiankama BF, Cush SS, Gibbs J, Bennink JR, Yewdell JW. CXCR3 chemokine receptor enables local CD8(+) T cell migration for the destruction of virus-infected cells. Immunity. 2015;42(3):524-37.
Das SR, Hensley SE, Ince WL, Brooke CB, Subba A, Delboy MG, Russ G, Gibbs JS, Bennink JR, Yewdell JW. Defining influenza A virus hemagglutinin antigenic drift by sequential monoclonal antibody selection. Cell Host Microbe. 2013;13(3):314-23.
Altman MO, Bennink JR, Yewdell JW, Herrin BR. Lamprey VLRB response to influenza virus supports universal rules of immunogenicity and antigenicity. Elife. 2015;4.