LY6E impairs coronavirus fusion and confers immune control of viral disease.
LY6E impairs coronavirus fusion and confers immune control of viral disease.
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DOI：
10.1038/s41564-020-0769-y
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发表时间：
2020-11
影响因子：
28.3
通讯作者：
Thiel V
中科院分区：
文献类型：
--
作者：
Pfaender S;Mar KB;Michailidis E;Kratzel A;Boys IN;V'kovski P;Fan W;Kelly JN;Hirt D;Ebert N;Stalder H;Kleine-Weber H;Hoffmann M;Hoffmann HH;Saeed M;Dijkman R;Steinmann E;Wight-Carter M;McDougal MB;Hanners NW;Pöhlmann S;Gallagher T;Todt D;Zimmer G;Rice CM;Schoggins JW;Thiel V
人畜共患冠状病毒（CoV）对全球健康构成重大威胁，二十年来出现的两种严重急性呼吸综合征冠状病毒（SARS-CoV和SARS-CoV-2）和中东呼吸综合征冠状病毒（MERS-CoV）就是例证。宿主对冠状病毒的免疫反应是复杂的，部分是通过抗病毒干扰素调节的。然而，干扰素刺激的抑制冠状病毒的基因产物并没有很好地表征。本研究表明，淋巴细胞抗原6复合体E位点（LY6E）能有效地限制多种冠状病毒的感染，包括SARS-CoV、SARS-CoV-2和MERS-CoV。机制研究表明LY6E通过干扰刺突蛋白介导的膜融合来抑制冠状病毒进入细胞。重要的是，造血细胞中缺乏Ly6e的小鼠对小鼠冠状病毒（小鼠肝炎病毒）高度敏感。在Ly6e基因敲除小鼠中，病毒发病机制的加剧伴随着肝脏免疫细胞的丧失、脾病毒负荷的增加和全局抗病毒基因通路的减少。因此，我们发现组成型Ly6e直接保护原代B细胞免受小鼠冠状病毒感染。我们的研究结果表明LY6E是一种关键的抗病毒免疫效应物，控制冠状病毒感染和发病机制。这些发现促进了我们对体外和体内免疫介导的冠状病毒控制的理解，这些知识可能有助于制定对抗新发冠状病毒感染的策略。
Zoonotic coronaviruses (CoVs) are significant threats to global health, as exemplified by the emergence of two severe acute respiratory syndrome CoVs (SARS-CoV and SARS-CoV-2) and Middle East respiratory syndrome CoV (MERS-CoV) within two decades. Host immune responses to CoVs are complex and regulated in part through antiviral interferons. However, interferon-stimulated gene products that inhibit CoVs are not well characterized. Here, we show that lymphocyte antigen 6 complex, locus E (LY6E) potently restricts infection by multiple CoVs, including SARS-CoV, SARS-CoV-2, and MERS-CoV. Mechanistic studies revealed that LY6E inhibits CoV entry into cells by interfering with spike protein-mediated membrane fusion. Importantly, mice lacking Ly6e in hematopoietic cells were highly susceptible to a murine CoV, mouse hepatitis virus. Exacerbated viral pathogenesis in Ly6e knockout mice was accompanied by loss of hepatic immune cells, higher splenic viral burden, and reduction in global antiviral gene pathways. Accordingly, we found that constitutive Ly6e directly protects primary B cells from murine CoV infection. Our results demonstrate that LY6E is a critical antiviral immune effector that controls CoV infection and pathogenesis. These findings advance our understanding of immune-mediated control of CoV in vitro and in vivo, knowledge that could help inform strategies to combat infection by emerging CoVs.
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DOI：
10.1016/j.bbi.2018.09.004
发表时间：
2018-11
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Ağaç D;Estrada LD;Maples R;Hooper LV;Farrar JD
通讯作者：
Farrar JD
影响因子：
64.8
作者：
Skarnes WC;Rosen B;West AP;Koutsourakis M;Bushell W;Iyer V;Mujica AO;Thomas M;Harrow J;Cox T;Jackson D;Severin J;Biggs P;Fu J;Nefedov M;de Jong PJ;Stewart AF;Bradley A
通讯作者：
Bradley A
影响因子：
--
作者：
Corman VM;Muth D;Niemeyer D;Drosten C
通讯作者：
Drosten C
DOI：
10.1146/annurev-virology-092818-015756
发表时间：
2019-01-01
期刊：
ANNUAL REVIEW OF VIROLOGY, VOL 6, 2019
影响因子：
--
作者：
Schoggins, John W.
通讯作者：
Schoggins, John W.
影响因子：
6.4
作者：
Qing, Enya;Hantak, Michael;Gallagher, Tom
通讯作者：
Gallagher, Tom