The SERINC (serine incorporator) proteins are host restriction factors that inhibit infection by HIV through their incorporation into virions. Here, we found that SERINC3 and SERINC5 exhibited additional antiviral activities by enhancing the expression of genes encoding type I interferons (IFNs) and nuclear factor κB (NF-κB) signaling. SERINC5 interacted with the outer mitochondrial membrane protein MAVS (mitochondrial antiviral signaling) and the E3 ubiquitin ligase and adaptor protein TRAF6, resulting in MAVS aggregation and polyubiquitylation of TRAF6. Knockdown of SERINC5 in target cells increased single-round HIV-1 infectivity, as well as infection by recombinant vesicular stomatitis virus (rVSV) bearing VSV-G or Ebola virus (EBOV) glycoproteins. Infection by an endemic Asian strain of Zika virus (ZIKV), FSS13025, was also enhanced by SERINC5 knockdown, suggesting that SERINC5 has direct antiviral activities in host cells in addition to the indirect inhibition mediated by its incorporation into virions. Further experiments suggested that the antiviral activity of SERINC5 was type I IFN–dependent. Together, these results highlight a previously uncharacterized function of SERINC proteins in promoting NF-κB inflammatory signaling and type I IFN production, thus contributing to its antiviral activities.

中文翻译：

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SERINC 蛋白增强抗病毒 I 型干扰素的产生和促炎信号通路

SERINC（丝氨酸掺入）蛋白是宿主限制因子，通过掺入病毒粒子来抑制 HIV 感染。在这里，我们发现 SERINC3 和 SERINC5 通过增强编码 I 型干扰素 (IFN) 和核因子 κB (NF-κB) 信号传导的基因的表达而表现出额外的抗病毒活性。SERINC5 与线粒体外膜蛋白 MAVS（线粒体抗病毒信号传导）和 E3 泛素连接酶和接头蛋白 TRAF6 相互作用，导致 MAVS 聚集和 TRAF6 的多泛素化。靶细胞中 SERINC5 的敲除增加了单轮 HIV-1 感染性，以及携带 VSV-G 或埃博拉病毒 (EBOV) 糖蛋白的重组水泡性口炎病毒 (rVSV) 的感染。亚洲流行的寨卡病毒 (ZIKV) 株 FSS13025 感染，SERINC5 敲低也增强了 SERINC5，这表明 SERINC5 除了通过掺入病毒粒子介导的间接抑制外，在宿主细胞中还具有直接的抗病毒活性。进一步的实验表明，SERINC5 的抗病毒活性是 I 型 IFN 依赖性的。总之，这些结果突出了 SERINC 蛋白在促进 NF-κB 炎症信号传导和 I 型 IFN 产生方面以前未被表征的功能，从而有助于其抗病毒活性。