Identification of cellular immune correlates of clinical disease and immune evasion strategies of varicella-zoster virus. (360G-Wellcome-089587_Z_09_Z)

We aim to determine why varicella-zoster virus elicits a poor circulating CD8+ cytotoxic T lymphocyte (CTL) response despite being an endogenous pathogen. First we will investigate whether such responses are adequately elicited at local sites of VZV replication in skin lesions compared to peripheral blood. We will then focus on understanding immune evasion mechanisms employed by the virus that potentially lead to an attenuated CD8+ CTL response including MHC-I down regulation and inadequate cell activation. We will finally proceed to identify the viral gene product(s) that interfere with specific MHC-I peptide processing and assembly pathways, and subsequent T cell activation. Specific Objectives 1. To identify the frequency, phenotype and effector function of immune cells present at cutaneous sites of VZV infection using lesional fluid from primary VZV infected individuals. 2. To characterise the MHC-I peptide assembly pathways that are arrested in VZV infected cells and potential viral genes responsible.