Laboratory of Viral Diseases

Jonathan W. Yewdell, M.D., Ph.D.
Jack R. Bennink, Ph.D.

Cellular Biology and Viral Immunology Sections, LVD

Description of Research Program

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

Video

Figure 6 movie (Windows Media Player)

Effect of PB1-F2 MTS-targeted protein on mitochondrial potential. HeLa cells expressing PB1-F2 65-87 EGFP and labeled with TMRE were imaged over 15 minutes’ time. The movie shows rapid loss of TMRE in transfected cells (indicated by arrows), which occurred within ~3 minutes. Images were acquired at 10-second intervals.

Lab Members

Meghan O’Donoghue Altman, Ph.D., Christopher Brooke, Ph.D., Mariana Pavon Eternod, Ph.D., Gregory Frank, Ph.D., William Ince, Ph.D., Xiuju Lu, Ph.D., Barbara Ngudiankama, Ph.D, and Mina Seedhom, Ph.D.

Research Staff

James Gibbs, Ph.D., Heather Hickman, Ph.D., Javier Magadan, Ph.D., Glennys Reynoso

Selected Publications

(View list in PubMed.)

Dolan BP, Sharma AA, Gibbs JS, Cunningham TJ, Bennink JR, Yewdell JW. MHC class I antigen processing distinguishes endogenous antigens based on their translation from cellular vs. viral mRNA. Proc Natl Acad Sci U S A. 2012 May 1;109(18):7025-30.

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 Apr 2;197(1):45-57.

Hickman HD, Li L, Reynoso GV, Rubin EJ, Skon CN, Mays JW, Gibbs J, Schwartz O,Bennink JR, Yewdell JW. Chemokines control naive CD8+ T cell selection of optimal lymph node antigen presenting cells. J Exp Med. 2011 Nov 21;208(12):2511-24.

Dolan BP, Knowlton JJ, David A, Bennink JR, Yewdell JW. RNA polymerase II inhibitors dissociate antigenic peptide generation from normal viral protein synthesis: a role for nuclear translation in defective ribosomal product synthesis? J Immunol. 2010 Dec 1;185(11):6728-33.

Netzer N, Goodenbour JM, David A, Dittmar KA, Jones RB, Schneider JR, Boone D, Eves EM, Rosner MR, Gibbs JS, Embry A, Dolan B, Das S, Hickman HD, Berglund P, Bennink JR, Yewdell JW, Pan T. Innate immune and chemically triggered oxidative stress modifies translational fidelity. Nature. 2009 Nov 26;462(7272):522-6.

Hensley SE, Das SR, Bailey AL, Schmidt LM, Hickman HD, Jayaraman A, Viswanathan K, Raman R, Sasisekharan R, Bennink JR, Yewdell JW. Hemagglutinin receptor binding avidity drives influenza A virus antigenic drift. Science. 2009 Oct 30;326(5953):734-6.

back to top