Picornavirus cell entry: Genome release and membrane penetration

小核糖核酸病毒进入细胞：基因组释放和膜穿透

• 批准号: G0600025/1
• 负责人: David Rowlands
• 金额: $ 45.68万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0600025%2F1
• 关键词: Picornavirus; cell; entry; Genome; release

The early stages in the life-cycle of a virus involves 1) attachment of the virus to a specific ?receptor? molecule on the surface of the cell and 2) transfer of the viral genetic material (nucleic acid ie. DNA or RNA) from within the virus, across the outer barrier of the cell membrane and into the cell. The viral DNA then directs the cell to make new virus. Clearly the process of delivering genetic material into the cell is a critical requirement for infection to occur. However for a certain class of viruses (the non-enveloped viruses) our knowledge of how the virus interacts with the cell membrane and how the nucleic acid is transferred into the cell is limited. It is important to understand these processes more fully as they present potential targets for therapeutic drugs. Designing such drugs requires intimate knowledge of the molecular interactions with the membrane that allow the nucleic acid entry into the cell. We have chosen to study the mechanism of cell entry of two closely related non-enveloped viruses: poliovirus and human rhinovirus (common cold virus) for the following reasons: 1) they are significant human pathogens, 2) they have been extensively studied for decades so that many of their other features (such as receptor binding) are well defined, 3) they are small, simple viruses that make good models for studying the cell entry of non-enveloped viruses in general.In recent years we have developed techniques in collaboration wih Professor Hogle (Harvard Medical School) for using spherical artificial membrane vesicles (liposomes) as model systems for studying the interactions between virus and membrane. We have recently shown that such systems can accurately mimic the early events seen in viral infection of the cell. This project seeks to extend the use of these models to broaden our knowledge of the molecular mechanisms involved in the essential first steps in virus infection. Our aim is to determine the mechanisms of RNA release from the virus and the transfer of RNA across the membrane.

病毒生命周期的早期阶段包括：1)病毒附着到特定的受体？细胞表面的分子和2)病毒遗传物质(核酸)的转移。DNA或RNA)从病毒内部穿过细胞膜的外部屏障进入细胞。然后，病毒DNA指导细胞制造新的病毒。显然，将遗传物质输送到细胞内的过程是发生感染的关键条件。然而，对于某一类病毒(非包膜病毒)，我们对病毒如何与细胞膜相互作用以及核酸如何转移到细胞内的了解是有限的。更充分地了解这些过程是很重要的，因为它们是治疗药物的潜在靶点。设计这样的药物需要深入了解允许核酸进入细胞的分子与细胞膜的相互作用。我们选择研究两种密切相关的非包膜病毒的细胞进入机制：脊髓灰质炎病毒和人类鼻病毒(普通感冒病毒)，原因如下：1)它们是重要的人类病原体；2)它们被广泛研究了几十年，因此它们的许多其他特征(如受体结合)得到了很好的定义；3)它们是小的、简单的病毒，可以作为研究一般非包膜病毒细胞进入的良好模型。近年来，我们与哈佛医学院霍格尔教授合作开发了一些技术，使用球形人工膜囊泡(脂质体)作为模型系统来研究病毒与膜之间的相互作用。我们最近已经证明，这种系统可以准确地模拟病毒感染细胞的早期事件。这个项目试图扩展这些模型的使用，以扩大我们对病毒感染基本第一步所涉及的分子机制的了解。我们的目的是确定RNA从病毒中释放和跨膜转移的机制。