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

人类染色体由端粒覆盖，端粒是由蛋白质结合的DNA序列，它们对人类基因组的稳定性至关重要。众所周知，端粒在细胞衰老和癌症进展中起着重要作用，因此确定和表征影响端粒的因素是很重要的。人类疱疹病毒6 （HHV-6）分为A和B两种亚型，与其他人类疱疹病毒不同，HHV-6可以插入染色体。当它这样做时，它总是插入端粒内或端粒旁边，但不知道这是否会影响端粒功能或是否会增加疾病风险。据估计，1%的英国人携带HHV-6病毒（CI-HHV-6）的综合拷贝，这种病毒通常遗传自父母，因此存在于身体的所有细胞中。在这个项目中，我们将确定染色体插入位点的性质，并利用这些信息来了解病毒是如何插入的，以及它在种系中插入的频率。我们将研究人类细胞如何控制病毒基因的表达，我们也将试图确定CI-HHV-6的存在是否影响体细胞和种系的端粒功能。

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.