Restriction of Influenza A Virus by SERINC5.
Restriction of Influenza A Virus by SERINC5.
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作者：
丝氨酸结合蛋白5(Ser5)是一种跨膜蛋白，最近被发现是一种针对人类免疫缺陷病毒(HIV)-1和小鼠白血病病毒(MLV)等伽玛逆转录病毒(MLV)的宿主抗病毒因子。它被HIV-1Nef和MLV糖蛋白所抵消。我们已经研究了它是否对甲型流感病毒(IAV)以及逆转录病毒具有抗病毒活性。在这里，我们证明了Ser5抑制了基于HIV-1的带有IAV血凝素(HA)的假病毒粒子；正如预期的那样，Ser5对该糖蛋白的作用被HIV-1Nef蛋白拮抗。我们发现Ser5明显通过与HA蛋白相互作用来抑制IAV的病毒-细胞和细胞-细胞融合。最重要的是，过表达和内源性的Ser5抑制了真正的IAV的感染。单分子荧光共振能量转移(SmFRET)分析进一步表明，Ser5既破坏了IAV HA融合前的构象稳定，又抑制了膜融合过程中卷曲螺旋的形成。Ser5在培养的小气道上皮细胞以及永生的人类细胞系中都有表达。综上所述，Ser5是一种抗IAV的宿主抗病毒因子，通过阻断HA诱导的膜融合发挥作用。
Serine incorporator 5 (Ser5), a transmembrane protein, has recently been identified as a host antiviral factor against human immunodeficiency virus (HIV)-1 and gammaretroviruses like murine leukemia viruses (MLVs). It is counteracted by HIV-1 Nef and MLV glycogag. We have investigated whether it has antiviral activity against influenza A virus (IAV), as well as retroviruses. Here, we demonstrated that Ser5 inhibited HIV-1-based pseudovirions bearing IAV hemagglutinin (HA); as expected, the Ser5 effect on this glycoprotein was antagonized by HIV-1 Nef protein. We found that Ser5 inhibited the virus-cell and cell-cell fusion of IAV, apparently by interacting with HA proteins. Most importantly, overexpressed and endogenous Ser5 inhibited infection by authentic IAV. Single-molecular fluorescent resonance energy transfer (smFRET) analysis further revealed that Ser5 both destabilized the pre-fusion conformation of IAV HA and inhibited the coiled-coil formation during membrane fusion. Ser5 is expressed in cultured small airway epithelial cells, as well as in immortal human cell lines. In summary, Ser5 is a host antiviral factor against IAV which acts by blocking HA-induced membrane fusion.
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DOI：
10.3390/v13071279
发表时间：
2021-06-30
期刊：
Viruses
影响因子：
--
作者：
Diehl WE;Guney MH;Vanzo T;Kyawe PP;White JM;Pizzato M;Luban J
通讯作者：
Luban J
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：
5.2
作者：
Liu, Yue;Wang, Hong;Zhang, Wenyan
通讯作者：
Zhang, Wenyan
影响因子：
5.4
作者：
Magnus, Carsten;Rusert, Peter;Regoes, Roland R.
通讯作者：
Regoes, Roland R.
影响因子：
11.4
作者：
Leikina, E;Ramos, C;Chernomordik, LV
通讯作者：
Chernomordik, LV