Recognition and evasion of Human cytomegalovirus by natural killer cells. (360G-Wellcome-094107_Z_10_Z)

Human cytomegalovirus (HCMV) provides a paradigm for how a complex viral pathogen persists and evades immune responses in humans. HCMV evades cytotoxic T cells by downregulating class I MHC, but then has to evade natural killer (NK) cells. We have recently described a novel MHC-like gene unique to clinical isolates that inhibits NK cell lysis by preventing the expression of NK cell activating ligands MICA and ULBP3. Recently we have discovered another viral gene (UL147) that prevent ULBP3 expres sion from very early post-infection. The specific goals of the work proposed are to:(i) Define the mechanism of action of the novel viral NK evasion gene product (UL147) (ii) Analyse the mechanisms that control NK cell recognition of HCMV in latently infected cells and during reactivation as all analysis to date has been on lytically infected cells. (iii) Address whether if particular NK cell subsets are refractory to HCMV mediated immune evasion and efficiently recognise HCMV infected cells?