Regulation of the integrated stress response to viral infection by RNA modifications

通过 RNA 修饰调节对病毒感染的综合应激反应

• 批准号: 2444832
• 金额: --
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2444832
• 关键词: Regulation; integrated; stress; response; viral

State primary research question and where appropriate the primary hypotheses being tested The hypothesis is that the m6A modifications have a role in the dynamic regulation of cellular and viral gene expression in the context of the integrated stress response and other antiviral pathways. The aim is to explore this hypothesis by generating human lung cell lines that are depleted in m6A writers, readers or erasers in combination with infection with influenza A virus or SARS-CoV-2. Importantly, these respiratory viruses have different replication strategies and interactions with the host cell. Viral replication in the context of modulating the m6A system and mutations in the viruses that sensitise them to the innate immune system will be analysed. The most robust phenotypes will be subjected to an unbiased (genome-wide) profiling of mRNA expression and translation with the outcomes functionally validated.

假设是m6A修饰在综合应激反应和其他抗病毒途径的背景下对细胞和病毒基因表达的动态调节中起作用。目的是通过产生在m6A写入器、读取器或擦除器中耗尽的人肺细胞系，并结合甲型流感病毒或SARS-CoV-2感染，来探索这一假设。重要的是，这些呼吸道病毒具有不同的复制策略和与宿主细胞的相互作用。病毒复制在调节m6A系统和病毒突变的背景下，使它们对先天免疫系统敏感，将被分析。最强大的表型将受到mRNA表达和翻译的无偏（全基因组）分析，并对结果进行功能验证。