How does the human papillomavirus (HPV) E5 protein control skin cell growth and differentiation during a productive life cycle?

人乳头瘤病毒 (HPV) E5 蛋白如何在生产生命周期中控制皮肤细胞的生长和分化？

• 批准号: 1647733
• 金额: --
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1647733
• 关键词: How; does; human; papillomavirus; HPV

Background: HPV infections are associated with diseases that impact both sexes including cervical cancer and head and neck squamous cell carcinoma (HNSCC). Despite the availability of a vaccine, current projections suggest that HPV-associated disease rates will not reduce significantly for several decades. To identify novel therapeutic targets that augment the vaccination strategy, it is vital to gain a greater understanding of the fundamental biology of HPV. HPV infection differs significantly from that of other viruses as it is tied to the differentiation status of the infected keratinocyte. Virions target proliferating basal stem cells in the epithelium, whilst virus-encoded proteins transform the hostile environment of the keratinocyte into one conducive for chronic infection. We identified the HPV E5 protein as a driver of unscheduled DNA replication and a delay in keratinocyte differentiation, both of which are required for efficient HPV replication in terminally differentiated keratinocytes. The proposed research will decipher the molecular basis for these observations.

背景资料：HPV感染与影响两性的疾病有关，包括宫颈癌和头颈部鳞状细胞癌（HNSCC）。尽管有疫苗可供使用，但目前的预测表明，HPV相关疾病的发病率在几十年内不会显著降低。为了确定增强疫苗接种策略的新治疗靶点，更好地了解HPV的基本生物学至关重要。HPV感染与其他病毒的感染显著不同，因为它与受感染的角质形成细胞的分化状态有关。病毒体靶向上皮中增殖的基底干细胞，而病毒编码的蛋白质将角质形成细胞的恶劣环境转化为有利于慢性感染的环境。我们确定了HPV E5蛋白作为非程序性DNA复制和角质形成细胞分化延迟的驱动因素，这两者都是在终末分化的角质形成细胞中有效HPV复制所需的。拟议中的研究将破译这些观察的分子基础。