SFTSV对宿主细胞自噬的影响及其分子机制的研究

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging viral pathogen that causes a high case fatality rate and has a broad range of distribution. SFTSV is a segmented single negative-strand RNA virus, belonging to Phlebovirus in the family Bunyaviridae. Studies on SFTSV interactions with its hosts were rare, especially on its immune evasion effect. Autophagy is an ancient and highly conserved intracellular degradation process, which plays an important role in host immunity against pathogen infection. Based on the knowledge of the genome sequence of isolated SFTSV, establishment of detection methods and studies on mechanisms of SFTSV evading from type I interferon response, we will study the evasion or inhibition effect of SFTSV on autophagy of host cells, and we will determine the molecular mechanism of SFTSV in regulating autophagy to promote replication of the virus, applying genetic engineering technology, protein technology and laser confocal microscopy. The outcome of our research will not only provide potential effective targets for development of new antiviral drug, but also provide scientific evidenc for prevention and control of SFTSV.

发热伴血小板减少综合征病毒（SFTSV）是一种新发的致死率高、流行范围广的急性传染性病毒病原，是一种分节段的单股负链RNA病毒，属于布尼亚病毒科白蛉病毒属成员。目前对其与宿主的相互作用机制，尤其是SFTSV逃逸宿主免疫反应方面的研究极少。自噬是细胞内古老而保守的物质降解过程，在清除入侵的病原体方面发挥重要作用。本研究在已经对分离出的SFTSV进行全基因组测序、检测方法的建立和对其逃逸宿主的I型干扰素反应机制进行了初步研究的基础上，拟利用基因工程技术、蛋白质学技术和激光共聚焦显微技术，对SFTSV逃逸或抑制宿主的自噬作用进行研究并阐明其如何调节宿主的自噬作用以有利于自身的复制，研究结果将为新型抗病毒药物的研制提供新的潜在有效靶标，也为SFTSV的预防和控制提供科学依据。

SFTSV是于中国发现的一种新型布尼亚负链RNA病毒、致死率高、流行范围广。至今对于其致病机制的报道仍然很少。自噬不仅在细胞维持自身代谢平衡，抵抗外界压力时发挥功能，其在多种病毒感染过程中也起到重要作用。然而SFTSV与自噬的相互作用机制目前仍不清楚。在本研究中，我们发现SFTSV感染可同时激活mTOR依赖的经典自噬和非经典的自噬信号通路。同时我们发现自噬在固有免疫限制RNA病毒SFTSV的增殖起重要作用。之后的研究表明SFTSV非结构蛋白NSs可在细胞内形成脂滴样结构，与LC3-II，p62或者Lamp2b存在共定位，且过表达NSs可显著激活自噬。总之，本研究首次阐明布尼亚病毒SFTSV与自噬的相互作用机制。