SLFN11抑制原型泡沫病毒复制的机制研究

泡沫病毒（FV）是反转录病毒科泡沫病毒亚科唯一种。其诸多特性与人类免疫缺陷病毒（HIV-1）等正反转录病毒相似，但感染个体后致病性迥异，表明宿主存在抑制FV复制的机制，成功阻断了FV感染。多项研究证明，包括干扰素刺激基因ISGs在内的固有免疫在其中发挥重要作用。SLFN家族蛋白受干扰素诱导表达、在DNA损伤修复中发挥重要作用。近来有文献报道其中SLFN11可抑制HIV-1及西尼罗河病毒（NWV）等慢病毒和黄病毒复制，可能是一类新的抗病毒ISGs，但其抗病毒种类、发挥功能的细胞范围及分子机制等诸多问题尚未明确。本课题组前期筛选性工作中发现，SLFN11可抑制原型泡沫病毒PFV在HT1080细胞中的复制。本项目拟在明确SLFN11抑制PFV复制作用特点的基础上，重点解析其抑制PFV的分子机制，初探PFV对其功能的影响，为深入理解病毒与宿主间制衡关系及制定新型病毒病防控策略提供理论支撑。

Foamy virus (FV), same as human immunodeficiency virus (HIV), belongs to the Retroviridae. There are many similarities between the two groups, such as the particle composition, the genome structure, the cytopathic effect of the tissue culture, and the host range. However, FV showed a lifelong latent infection and no disease was found till now, while HIV cause AIDS. It is certain that there are some mechanisms that inhibit FV replication in the host, which successfully block FV infection. There are some evidences that innate immunity, including interferon inducible genes, plays an important role in FV latency. SLFN family proteins can be induced by interferon and play an important role in DNA damage and repair. In recent years, it has been reported that SLFN11 can inhibit the replication of human immunodeficiency virus (HIV-1), West Nile virus (NWV) and other lentiviruses and flaviviruses, which may represent a new kind of ISGS that can inhibit the translation process of virus proteins. However, the types of antiviral, the types of functional cell and the molecular mechanism are unknown. Our recent results of screening assay and some confirmatory tests showed that SLFN11 could inhibit the prototype foamy virus (PFV) replication in HT080. Here, we apply to explore the mechanism of SLFN11 inhibition of PFV replication. Meanwhile，we will try to find the some details in the relationship between TRIM14 and PFV replication. The aim of the project is to provide experimental basis for the understanding of antiviral mechanism of SLFN family. The results will provide theoretical supports to understand the relationship between the virus and the host, and may help us to develop some new strategies to prevent the diseases caused by viruses.