Immunopathogenesis of varicella zoster virus infection

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Varicella zoster virus (VZV) is a herpesvirus which infects up to 90% of the population. VZV causes chicken pox (varicella) predominantly in childhood and shingles (herpes zoster) in middle to old age people. Whilst VZV usually causes relatively mild disease in healthy individuals, VZV still causes significant morbidity in children and adults. VZV causes life-threatening disease in immunocompromised individuals such as patients who are elderly or have HIV disease. Shingles affects many elderly individuals and a major complication is prolonged severe pain or post-herpetic neuralgia (PHN), which can be severely debilitating and often requires follow-up medical care for months or even years after the initial attack. Despite its significant impact on the community, little is known about how this virus functions and causes disease. This project aims to improve our understanding of how VZV infection affects specialised human cells in order to provide novel information for the development of therapies aimed at lessening the impact of VZV disease on the community. This project has four components: (1) We will continue studies which have shown that VZV causes programmed cell death (apoptosis) in human skin cells (fibroblasts) but not human nerve cells (neurons). We aim to identify viral genes responsible for the cell-type specific modulation of apoptosis in human neurons and fibroblasts (2) We will examine human sensory ganglia (clusters of human nerve cells) during shingles and determine what immune cells are present and whether neurons are undergoing apoptosis (3) To assess the impact of VZV infection on the ability of specialized immune cells (called dendritic cells) to mature properly (4) We have shown that VZV may actively avoid immune detection by interfering with the function of dendritic cells. We aim to identify the mechanism responsible for the virus interfering with the expression of immune molecules which are essential for our immune system.