What are the determinants of Varicella Zoster Virus Tropism within skin cells? Determinants of localisation of varicell

Approximately 600,000 cases of varicella-zoster (chicken-pox/shingles) infection occur in the UK per annum, and the economic burden of VZV is estimated to be over £200 million per annum in the UK. A live attenuated vaccine, vOka strain, has been licensed since 2003 in the UK. The vaccine is effective and safe. However, vaccine-associated fever and rash occur in 5% of patients, which can be life-threatening in those with immunodeficiency. For this reason, the vaccine cannot be given to patients most at risk of serious varicella infections, including patients with HIV and organ transplant recipients. Hence, there remains a great clinical need to provide better vaccines, and treatments. By comparing the differences between parent Oka and vaccine Oka in expression and growth in various skin cells, we aim to identify the determinants of VZV replication. Since replication in skin is central to the natural history of VZV, a better understanding of how the virus interacts with epithelial tissues will improve our knowledge of its pathogenesis. The results will inform the development of improved vaccines. It will also provide the basis for future studies to examine VZV as a tool for delivery of drugs and genes to the skin.

Approximately 600,000 cases of varicella-zoster virus (VZV) infection occur in the UK per annum, and the economic burden of VZV is estimated to be over £200 million per annum. HZ occurring in up to 40% of immunosuppressed patients accounts for cases requiring hospitalization. A live attenuated vaccine, vOka strain, is licensed for immunisation of children in the USA against chickenpox and for health care workers in the UK. The vaccine is effective and safe. However, vaccine-associated fever and rash occur in 5% of patients, which can be life-threatening in those with unidentified immunodeficiency. For this reason, the vaccine cannot be given to immunocompromised patients most at risk of serious varicella infections. The selective attenuation of replication of the Oka vaccine within differentiated skin cells provides a molecular tool to explore the mechanisms by which the wild type virus normally infects keratinocytes. By comparing the differences between pOka and vOka in infection, gene expression and growth in various skin cells (such as keratinocytes, melanocytes and hair follicle cells), we aim to identify the determinants of VZV tropism and replication in skin. Since replication in skin is central to the natural history of VZV, a better understanding of how the virus interacts with epithelial tissues will improve our knowledge of its pathogenesis. Importantly, the results will inform the development of novel, improved vaccines to prevent chickenpox and shingles. The data will also provide the basis for future studies to examine VZV as a tool for delivery of drugs and genes to the skin.