SERINC proteins potentiate antiviral type I IFN production and proinflammatory signaling pathways.
SERINC proteins potentiate antiviral type I IFN production and proinflammatory signaling pathways.
复制标题
SERINC蛋白增强抗病毒I型IFN的产生和促炎信号通路。
DOI：
10.1126/scisignal.abc7611
复制
发表时间：
2021-09-14
影响因子：
7.3
通讯作者：
Liu, Shan-Lu
中科院分区：
文献类型：
--
作者：
Zeng, Cong;Waheed, Abdul A.;Li, Tianliang;Yu, Jingyou;Zheng, Yi-Min;Yount, Jacob S.;Wen, Haitao;Freed, Eric O.;Liu, Shan-Lu
丝氨酸结合子（SERINC）蛋白是宿主限制因子，通过与病毒粒子结合抑制HIV感染。在这里，我们发现SERINC3和SERINC5通过增强编码I型干扰素（IFNs）和核因子κB （NF-κB）信号的基因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）、E3泛素连接酶和接头蛋白TRAF6相互作用，导致MAVS聚集和TRAF6多泛素化。在靶细胞中敲低SERINC5增加了单轮HIV-1的传染性，以及携带VSV-G或埃博拉病毒（EBOV）糖蛋白的重组水疱性口炎病毒（rVSV）的感染。亚洲寨卡病毒（ZIKV）株FSS13025的感染也被SERINC5敲低，这表明SERINC5除了通过并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产生方面的先前未被描述的功能，从而有助于其抗病毒活性。
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.
登录
查看更多内容
影响因子：
6.4
作者：
Ahi YS;Zhang S;Thappeta Y;Denman A;Feizpour A;Gummuluru S;Reinhard B;Muriaux D;Fivash MJ;Rein A
通讯作者：
Rein A
影响因子：
29.7
作者：
Brubaker SW;Bonham KS;Zanoni I;Kagan JC
通讯作者：
Kagan JC
影响因子：
30.5
作者：
Kawai, T;Takahashi, K;Akira, S
通讯作者：
Akira, S
影响因子：
30.3
作者：
Galão RP;Le Tortorec A;Pickering S;Kueck T;Neil SJ
通讯作者：
Neil SJ
DOI：
10.3390/v7122970
发表时间：
2015-12-19
期刊：
Viruses
影响因子：
--
作者：
Fackler OT
通讯作者：
Fackler OT