CD8+ T-cells play a crucial role in eradicating viral infections. The focus of this project is two-fold. First, to study general in vivo mechanisms of virus - host interactions and second, to understand how primary and memory T-cells respond to virus infection. Despite the importance of T-cells, we do not yet fully understand the induction of a CD8+ T-cell responses and the generation of CD8+ T-cell memory to virus infection. For viruses in which traditional vaccine approaches have not been successful, it is hoped that induction of CD8+ T-cell memory will enhance immunity. To induce optimal CD8+ T-cell responses to vaccines it is necessary to understand how primary CD8+ T-cells are stimulated. This project aims to address questions related to the optimal and activation of T cell immunity following primary and secondary virus infection by studying several viruses and different routes of infection. This year our studies examining a poxvirus skin infection have demonstrated distinct roles for innate and adaptive immune cells in virus clearance.

Project Start
Project End
Budget Start
Budget End
Support Year
17
Fiscal Year
2013
Total Cost
$748,434
Indirect Cost
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State
Country
Zip Code
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
Zanker, Damien; Waithman, Jason; Yewdell, Jonathan W et al. (2013) Mixed proteasomes function to increase viral peptide diversity and broaden antiviral CD8+ T cell responses. J Immunol 191:52-9
Hensley, Scott E; Pinto, Amelia K; Hickman, Heather D et al. (2009) Murine norovirus infection has no significant effect on adaptive immunity to vaccinia virus or influenza a virus. J Virol 83:7357-60