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

研究人类疱疹病毒 6 (HHV6) 染色体整合对端粒分子生物学的影响。

• 批准号: G0901657/1
• 负责人: Nicola Royle
• 金额: $ 53.67万
• 依托单位: University of Leicester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0901657%2F1
• 关键词: Investigation; impact; chromosomal; integration; human

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.

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。现在众所周知，端粒在细胞衰老中起重要作用，这有助于衰老，并且在癌症进展中起重要作用，因此识别和鉴定影响端粒的因素是重要的。人类疱疹病毒6（HHV-6）有两种亚型，A和B，与其他人类疱疹病毒不同，HHV-6可以将自身插入染色体。当它这样做时，它总是插入端粒中或旁边，但不知道这是否会影响端粒功能或是否会导致疾病风险增加。据估计，1%的英国人口携带HHV-6病毒（CI-HHV-6）的整合拷贝，该病毒通常从父母遗传，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，以及它在生殖系中实现插入的频率。我们将研究人类细胞如何控制病毒基因的表达，我们还将试图确定CI-HHV-6的存在是否影响体细胞和生殖系中的端粒功能。