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Nat Immunol：抗病毒天然免疫表观调控获进展

2017-09-01 佚名 中国科学报

免疫病毒
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《自然—免疫学》杂志8月29日发表了中国医学科学院院长、中国工程院院士曹雪涛研究团队的论文，报道了RNA解旋酶DDX46能够通过RNA去甲基化修饰导致抗病毒效应分子mRNA核滞留、进而抑制抗病毒天然免疫应答的研究结果。

《自然—免疫学》杂志8月29日发表了中国医学科学院院长、中国工程院院士曹雪涛研究团队的论文，报道了RNA解旋酶DDX46能够通过RNA去甲基化修饰导致抗病毒效应分子mRNA核滞留、进而抑制抗病毒天然免疫应答的研究结果。

干扰素在机体抗病毒天然免疫应答中发挥关键性的作用。在病毒感染过程中，干扰素产生的多少与持续时间受到精确调控，以确保机体清除入侵病毒的同时能避免病理性自身免疫损伤。目前关于干扰素表达精确调控的分子机制研究主要集中在天然免疫信号通路蛋白分子，而以细胞核内RNA修饰的方式调控干扰素表达的机制尚不清楚。

曹雪涛院士与中国医学科学院基础所博士后郑青亮以及第二军医大学医学免疫学国家重点实验室教授侯晋联合攻关，针对DEAD-box解旋酶(DDX)家族成员在RNA识别和代谢及其在调控抗病毒天然免疫应答中发挥的重要功能，通过筛选多种DDX家族成员在病毒感染巨噬细胞天然免疫应答中的作用，发现了DDX46能显著抑制病毒感染诱导的干扰素表达。

研究表明，DDX46能结合到抗病毒效应分子mRNA的CCGGUU保守基序上，当病毒感染时DDX46与m6A去甲基化酶ALKBH5结合增加，使得与DDX46结合的抗病毒效应分子mRNA发生去甲基化修饰而导致其核滞留，阻滞了这些抗病毒效应分子的蛋白表达从而降低干扰素产生，最终抑制了抗病毒天然免疫应答反应。

本研究揭示了RNA解旋酶DDX46在细胞核内通过RNA修饰的新方式参与调控抗病毒天然免疫应答，提出了一种新的天然免疫与炎症调控机制，为病毒感染和炎症性疾病的防治提供了新的潜在靶标与思路。

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    2018-08-11 liye789132251

    #Nat#

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    2017-09-15 sodoo

    #表观调控#

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    2017-09-03 yahu

    #抗病毒#

    0

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    2017-09-03 仁心济世

    #天然免疫#

    0

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