病毒基因组m6A修饰近几年成为病毒学研究热点，人类免疫缺陷病毒(HIV)、流感病毒和黄病毒等病毒基因组含有m6A修饰并调控病毒基因的表达和复制。m6A修饰与免疫通路之间的联系，在细胞质内复制的负链RNA病毒（如发热伴血小板减少综合征病毒，SFTSV）的m6A修饰及功能目前尚无报道。我们发现肠病毒71型（EV71）及SFTSV都含有m6A修饰且调控病毒复制，EV71 RNA m6A修饰和甲基转移酶METTL3促进病毒免疫逃逸。本项目拟以EV71为对象研究病毒m6A修饰、METTL3、结合蛋白YTHDF2和YTHDF3通过与免疫系统相互作用调控病毒复制的分子机制；以SFTSV为对象研究宿主m6A修饰系统与病毒复制之间的关系，探索病毒关键非结构蛋白参与m6A调控病毒复制的分子机制。本项目不仅有助于从表观遗传学的角度了解病毒复制及免疫应答，而且可能为病毒防治提供新的思路和药物靶标。

Viral genomic N6 methyladenosine (m6A) modification modulates viral replication and becomes a hot topic in viral research recently. It has been reported that HIV, Influenza virus and Dengue virus contain m6A nucleotides which modulate viral gene expression and replication. However, it is unknown whether m6A modification is involved in immune escape and Severe fever with thrombocytopenia syndrome virus （SFTSV）replication. Our previous study showed that EV71 and SFTSV genomic RNA harbor m6A residues and regulate viral replication. Importantly, m6A modification and methyltransferase METTL3 facilitate EV71 escape the immune surveillance. The aim of this project is to understand the detailed mechanism how m6A regulate EV71 and SFTSV replication. The interaction among m6A modification, METTL3, YTHDF2, YTHDF3 and immune response pathways will be studied in EV71 infection to elucidates the mechanism of virus immune escape. We will also check how host m6A machinery influences SFTSV replication to study the mechanism that non-structural proteins interacts with m6A complex. This project helps not only to understand the mechanism how m6A regulates viral replication, but also to provide new method and target to treat viral infection.