Jonathan W. Yewdell, M.D., Ph.D.
Jack R. Bennink, Ph.D.
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)
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| 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
Tshaka Cunningham, Ph.D., Alexandre David, Ph.D., Suman Das, Ph.D., Brian Dolan, Ph.D., Kristie Grebe, Ph.D., Scott Hensley, Ph.D., Avital Lev, Ph.D., Nir Netzer, Ph.D., Jeffrey Ishizuka, and Eugene Shenderov
Research Staff
James Gibbs, Ph.D., Heather Hickman, Ph.D., Kazuyo Takeda, M.D., Ph.D., Glennys Reynoso
Selected Publications
(View list in PubMed.)
McAuley JL, Hornung F, Boyd KL, Smith AM, McKeon R, Bennink J, Yewdell JW, McCullers JA. The 1918 Influenza A Virus PB1-F2 Enhances the Pathogenesis of Viral and Secondary Bacterial Pneumonia. 2007. Cell Host & Microbe, 2:240-249.
Hickman HD, Takeda K, Skon CN, Murray FR, Hensley SE, Loomis J, Barber GN, Bennink JR, Yewdell JW. Direct priming of anti-viral CD8+ T cells in the peripheral interfollicular region of lymph nodes. 2008. Nature Immunology 9:155-165.
Yewdell JW. How to Succeed in Science: A Concise Guide for Young Scientists. Part I. Taking the Plunge. 2008. Nature Rev. Cell Mol. Biol. in press.
Yewdell JW. How to Succeed in Science: A Concise Guide for Young Scientists. Part II. Making Discoveries. 2008. Nature Rev. Cell Mol. Biol. in press.
Lev A, Takeda K, Zanker D, Maynard JC, Dimberu P, Waffarn E, Gibbs J, Netzer N, Princiotta MF, Neckers L, Picard D, Nicchitta CV, Chen W, Reiter Y, Bennink JR, Yewdell JW. The Exception that Reinforces the Rule: Cross-Priming by Cytosolic Peptides that Escape Degradation. 2008. Immunity, in press.
Yewdell JW, Pierson TC, Bennink JR. (2008). Immune response to viruses. In: Clinical Virology 2nd Edition (D.D. Richman, R.J. Whitely, F.G. Hayden, eds.). Churchill Livingstone, New York.
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