Investigation of the impact chromosomal integration of human herpes virus 6 (HHV6) has on telomere molecular biology.

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Human chromosomes are capped by telomeres, which are DNA sequences bound by proteins and they are essential for the stability of the human genome. It is now well known that telomeres play important roles in cellular senescence, which contributes to ageing, and in cancer progression thus it is important to identify and characterise factors that influence telomeres. The human herpesvirus 6 (HHV-6) occurs in two subtypes, A and B, and unlike other human herpes viruses, HHV-6 can insert itself into a chromosome. When it does this it always inserts in or next to a telomere but it is not known if this affects telomere function or whether it contributes to an increased risk of disease. It has been estimated that 1% of the UK population carry an integrated copy of the HHV-6 virus (CI-HHV-6) that is often inherited from a parent and so it is present in all cells of the body. In this project we will determine the nature of the chromosomal insertion site and use the information to understand how the virus inserts and how frequently it achieves this in the germ-line. We will investigate how the human cell controls expression of the viral genes and we will also try to determine whether the presence of CI-HHV-6 affects telomere function in somatic cells and in the germ-line.