Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, 750 Republican St, Seattle, WA, USA; Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, No. 1, Changde St, Taipei City, Taiwan.
Center for Advanced Biotechnology and Medicine, Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ, USA.
EBioMedicine. 2016 Jul;9:195-206. doi: 10.1016/j.ebiom.2016.06.015. Epub 2016 Jun 11.
Retinoic acid inducible gene-I (RIG-I) is a cytosolic pathogen recognition receptor that initiates the immune response against many RNA viruses. Upon RNA ligand binding, RIG-I undergoes a conformational change facilitating its homo-oligomerization and activation that results in its translocation from the cytosol to intracellular membranes to bind its signaling adaptor protein, mitochondrial antiviral-signaling protein (MAVS). Here we show that RIG-I activation is regulated by reversible acetylation. Acetyl-mimetic mutants of RIG-I do not form virus-induced homo-oligomers, revealing that acetyl-lysine residues of the RIG-I repressor domain prevent assembly to active homo-oligomers. During acute infection, deacetylation of RIG-I promotes its oligomerization upon ligand binding. We identify histone deacetylase 6 (HDAC6) as the deacetylase that promotes RIG-I activation and innate antiviral immunity to recognize and restrict RNA virus infection.
视黄酸诱导基因-I（RIG-I）是一种胞质病原体识别受体，可引发针对多种 RNA 病毒的免疫反应。在 RNA 配体结合后，RIG-I 发生构象变化，促进其同源寡聚化和激活，从而使其从细胞质易位到细胞内膜以结合其信号转导衔接蛋白，线粒体抗病毒信号蛋白（MAVS）。在这里，我们表明 RIG-I 的激活受到可逆乙酰化的调节。RIG-I 的乙酰模拟突变体不能形成病毒诱导的同源寡聚体，这表明 RIG-I 抑制结构域的乙酰化赖氨酸残基阻止其组装成活性同源寡聚体。在急性感染期间，RIG-I 的去乙酰化作用促进其在配体结合时寡聚化。我们确定组蛋白去乙酰化酶 6（HDAC6）为促进 RIG-I 激活和先天抗病毒免疫的去乙酰化酶，以识别和限制 RNA 病毒感染。
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