Human cytomegalovirus (HCMV) provides a paradigm for how a complex viral pathogen persists and evades immune responses. Our programme of research seeks to addressed a number of important questions concerning the immunobiology of HCMV. With a particular focus on the generation, maintanance and funtion of memory CD8+ T cells and the immune evasion mechanism employed by the virus to modulate Natural Killer cell function.
Our longitudinal study of primary HCMV infection has shown that T cell receptor affinity appears crucial for the selection of T cells into long-term memory from the initial highly polyclonal T cell response. This process is not stochastic, as in many murine models, and is remarkably rapid, occurring over weeks not years. Selected T cell clones are very long lived – possibly retained for life.
Mason, G. M., E. Poole, J. G. Sissons, J. H. Sinclair, and M. R. Wills. 2012. Human cytomegalovirus latency alters the cellular secretome, inducing cluster of differentiation (CD)4+ T-cell migration and suppression of effector function. Proceedings of the National Academy of Sciences of the United States of America 4;109(36):14538-43.
Bennett NJ, Ashiru O, Morgan FJ, Pang Y, Okecha G, Eagle RA, Trowsdale J, Sissons JG, Wills MR (2010) Intracellular sequestration of the NKG2D ligand ULBP3 by human cytomegalovirus J Immunol Jul 15; 185(2): 1093-102