Synaptogyrin-2 Promotes Replication of a Novel Tick-borne Bunyavirus through Interacting with Viral Nonstructural Protein NSs
Synaptogyrin-2 Promotes Replication of a Novel Tick-borne Bunyavirus through Interacting with Viral Nonstructural Protein NSs
复制标题
Synaptogyrin-2 通过与病毒非结构蛋白 NS 相互作用促进新型蜱传布尼亚病毒的复制
DOI：
10.1074/jbc.m116.715599
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发表时间：
2016-07-29
影响因子：
4.8
通讯作者：
Xing, Zheng
中科院分区：
文献类型：
--
作者：
Sun, Qiyu;Qi, Xian;Xing, Zheng
Synaptogyrin-2 是突触环蛋白家族的非神经元成员，参与突触小泡的生物发生和运输。人们对 synaptogyrin-2 的功能知之甚少。严重发热伴血小板减少综合征（SFTS）是一种新发传染病，以高烧、血小板减少和白细胞减少为特征，死亡率高，由布尼亚病毒科一种新型蜱传白斑病毒引起。我们之前的研究表明，病毒非结构蛋白 NS 形成包涵体 (IB)，参与病毒免疫逃避以及病毒 RNA 复制。在这项研究中，我们试图阐明 NS 形成 IB 的机制，IB 是一种基于脂滴的结构，通过 NS 与周脂肪素 A 和脂肪分化相关蛋白 (ADRP) 的共定位得到证实。通过高通量筛选，我们发现 synaptogyrin-2 在响应 SFTS 布尼亚病毒 (SFTSV) 感染时高度上调，并且是病毒复制的促进剂。我们证明了 synaptogyrin-2 与 NS 相互作用并易位到 IB 中，IB 在感染中从脂滴重建为大型结构。当在特定 shRNA 表达细胞中沉默 synaptogyrin-2 时，病毒 RNA 复制减少，感染性病毒滴度显着降低，这与从常规脂滴重组的大 IB 数量减少相关。我们假设 synaptogyrin-2 通过与 NS 相互作用，对于促进 IB 的形成成为病毒 RNA 复制的病毒工厂至关重要。这些发现揭示了 synaptogyrin-2 作为病毒感染增强剂的功能。
Synaptogyrin-2 is a non-neuronal member of the synaptogyrin family involved in synaptic vesicle biogenesis and trafficking. Little is known about the function of synaptogyrin-2. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease characterized by high fever, thrombocytopenia, and leukocytopenia with high mortality, caused by a novel tick-borne phlebovirus in the family Bunyaviridae. Our previous studies have shown that the viral nonstructural protein NSs forms inclusion bodies (IBs) that are involved in viral immune evasion, as well as viral RNA replication. In this study, we sought to elucidate the mechanism by which NSs formed the IBs, a lipid droplet-based structure confirmed by NSs co-localization with perilipin A and adipose differentiation-related protein (ADRP). Through a high throughput screening, we identified synaptogyrin-2 to be highly up-regulated in response to SFTS bunyavirus (SFTSV) infection and to be a promoter of viral replication. We demonstrated that synaptogyrin-2 interacted with NSs and was translocated into the IBs, which were reconstructed from lipid droplets into large structures in infection. Viral RNA replication decreased, and infectious virus titers were lowered significantly when synaptogyrin-2 was silenced in specific shRNA-expressing cells, which correlated with the reduced number of the large IBs restructured from regular lipid droplets. We hypothesize that synaptogyrin-2 is essential to promoting the formation of the IBs to become virus factories for viral RNA replication through its interaction with NSs. These findings unveil the function of synaptogyrin-2 as an enhancer in viral infection.