Regulation of the expression of Human Endogenous Retrovirus envelope genes and analysis of their function

人内源性逆转录病毒包膜基因的表达调控及其功能分析

• 批准号: 298527-2013
• 负责人: Barbeau, Benoit
• 金额: $ 2.62万
• 依托单位: Université du Québec à Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=548360
• 关键词: Regulation; expression; Human; Endogenous; Retrovirus

The human genome harbours sequences, which originate from viruses known as retroviruses. It has been estimated that about 8% of human DNA is composed of these retroviral sequences. These sequences have been integrated in the genome of primates 25 million years ago. Although most of these DNA regions are no longer capable of producing viruses, some have been reported to have retained the capacity to generate viruses, which, although non-infectious, can be observed in the extracellular milieu. These viruses are termed Human Endogenous Retroviruses (HERV). The presence of HERVs in the human organism has been rarely associated with biological phenomena, although four HERV proteins termed Syncytin-1, Syncytin-2, EnvV2 and EnvP(b) representing the envelope proteins of ancient retroviruses could be important for the development of the placenta. Based on our previous results, we are interested in testing their involvement in placenta development through the study of the mechanism of regulation of their expression in trophoblasts (placenta-derived cells), their localisation inside the cell and by analysing their impact on differentiation of these cells and immunosuppression linked to the placenta. Several tools (including specific antibodies, new chimeric proteins and RNA interference-based RNA molecules) will be used in this study to understand the implication of these retrovirus-related proteins in the various roles that are attributed to trophoblasts. These experiments will shed light on the mechanism of action and the mode of regulation of expression of these genes with relation ot the placenta and are therefore part of a fundamental research program. These results will bring a new light on how these HERV genes are turned on in trophoblasts and how they affect important biological processes and functions associated to the placenta.

人类基因组含有序列，这些序列来自称为逆转录病毒的病毒。据估计，约8%的人类DNA由这些逆转录病毒序列组成。这些序列在2500万年前已经整合到灵长类动物的基因组中。尽管这些DNA区域中的大多数不再能够产生病毒，但据报道，一些DNA区域保留了产生病毒的能力，尽管这些病毒不具有感染性，但可以在细胞外环境中观察到。这些病毒被称为人类内源性逆转录病毒（HERV）。人类生物体中HERV的存在很少与生物学现象相关，尽管四种HERV蛋白（称为合胞素-1、合胞素-2、EnvV 2和EnvP（B））代表古老逆转录病毒的包膜蛋白可能对胎盘的发育很重要。基于我们以前的结果，我们有兴趣通过研究它们在滋养层细胞（胎盘衍生细胞）中表达的调节机制，它们在细胞内的定位以及通过分析它们对这些细胞分化的影响和与胎盘相关的免疫抑制来测试它们参与胎盘发育。本研究将使用几种工具（包括特异性抗体，新的嵌合蛋白和基于RNA干扰的RNA分子）来了解这些逆转录病毒相关蛋白在滋养层中的各种作用。这些实验将阐明这些基因与胎盘相关的作用机制和表达调控模式，因此是基础研究计划的一部分。这些结果将为这些HERV基因如何在滋养层中打开以及它们如何影响与胎盘相关的重要生物过程和功能带来新的认识。