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摘要 : 2017年7月12日,国际著名学术杂志《Cell》子刊、著名病原微生物学期刊《Cell Host Microbe》杂志在线发表了武汉大学生命科学学院钟波教授课题组和黄赞教授课题组在抗病毒天然免疫研究方面取得重要进展。

2017年7月12日,国际著名学术杂志《Cell》子刊、著名病原微生物学期刊《Cell Host Microbe》杂志在线发表了武汉大学生命科学学院钟波教授课题组和黄赞教授课题组在抗病毒天然免疫研究方面取得重要进展。研究成果题为“Induction of INKIT by viral infection negatively regulates antiviralresponses through inhibiting phosphorylation of p65 and IRF3”,研究被评为当期封面文章。该文阐述了INKIT蛋白通过抑制转录因子IRF3和p65的磷酸化,从而负调控抗病毒天然免疫反应的过程。黄赞课题组2012级博士生鲁斌、孙雪琴和钟波课题组2015级博士生任玉洁为共同第一作者,钟波教授和黄赞教授为共同通讯作者。

IRF3和p65是病毒诱导的下游抗病毒基因转录过程中重要的转录因子。该研究小组发现INKIT (inhibitor for NF-kB and IRF3) 通过抑制IRF3和p65的磷酸化,从而抑制宿主抗病毒天然免疫应答。在INKIT敲除的细胞中,IRF3和p65的磷酸化明显增强,从而促进了病毒感染诱导干扰素和炎性细胞因子等下游基因的表达。INKIT敲除的小鼠对于病毒HSV-1或者VSV感染更加具有抵抗性,小鼠体内的病毒复制水平降低,暗示着INKIT在调控抗病毒免疫应答过程中有着关键作用。


Induction of INKIT by Viral Infection Negatively Regulates Antiviral Responses through Inhibiting Phosphorylation of p65 and IRF3


The transcription factors p65 and IRF3 play key roles in the induction of cellular antiviral responses. Phosphorylation of p65 and IRF3 is required for their activity and constitutes a key checkpoint. Here we report that viral infection induced upregulation of INKIT, an inhibitor for NF-κB and IRF3 that restricted innate antiviral responses by blocking phosphorylation of p65 and IRF3. INKIT overexpression inhibited virus-induced phosphorylation of p65 and IRF3 and expression of downstream genes. In contrast, knockdown or knockout of INKIT had the opposite effect: Inkit−/−mice produced elevated levels of type I interferons and proinflammatory cytokines and were more resistant to lethal viral infection compared to wild-type. INKIT interacted with IKKα/β and TBK1/IKKɛ, impairing the recruitment and phosphorylation of p65 and IRF3. Viral infection induced IKK-mediated phosphorylation of INKIT at Ser58, resulting in its dissociation from the IKKs. Our findings thus uncover INKIT as a regulator of innate antiviral responses.

来源: Cell Host & Microbe 浏览次数:0


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