Boosting stem cell immunity to viruses.

Boosting stem cell immunity to viruses.
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DOI:
10.1126/science.abj5673
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发表时间:
2021-07-09
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Ding SW
Ding SW
中科院分区:
其他
文献类型:
--
作者:
Shahrudin S;Ding SW

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哺乳动物干细胞在干扰素(IFN)调节的先天免疫功能方面存在缺陷,因此它们依赖某些干扰素刺激基因(ISGs)(1)和ArgAerte 2(AGO2)依赖的RNA干扰(RNAi)(2,3)的结构性表达来提供抗病毒保护。哺乳动物抗病毒RNAi是由DICER发起的,它将病毒双链RNA(DsRNA)复制中间产物加工成小干扰RNA(SiRNAs),作为RNA诱导的沉默复合体[(RISC包含AGO2](2-10))切割病毒RNA的特异性决定因素。然而,干细胞如何激活抗病毒RNAi尚不清楚,因为DicerR的缺失矛盾地增强了小鼠胚胎干细胞对病毒的抵抗力(11)。在本期第231页上,Poirieret等人(12)表明,小鼠和人类干细胞具有一种特殊的DICER亚型,用于产生病毒衍生的siRNA(VsiRNA),以启动有效的抗病毒RNAi。这进一步表明,siRNA治疗策略可能适用于寨卡病毒(ZIKV)和严重急性呼吸综合征冠状病毒2(SARS-CoV-2)等RNA病毒。
Mammalian stem cells exhibit deficiencies in innate immunity regulated by interferons (IFNs), so they rely on constitutive expression of some IFN-stimulated genes (ISGs) (1) and Argonaute 2 (AGO2)–dependent RNA interference (RNAi) (2,3) for antiviral protection. Mammalian antiviral RNAi is initiated by Dicer, which processes viral double-stranded RNA (dsRNA) replicative intermediates into small interfering RNAs (siRNAs) that act as specificity determinants for viral RNA cleavage by RNA-induced silencing complex [(RISC) which contains AGO2] (2–10). However, it remains unclear how stem cells activate antiviral RNAi because deletion ofDicerparadoxically enhances virus resistance in mouse embryonic stem cells (11). On page 231 of this issue, Poirieret al.(12) show that mouse and human stem cells have a specialized Dicer isoform for virus-derived siRNA (vsiRNA) production to initiate potent antiviral RNAi. This further indicates that siRNA therapeutic strategies may be viable for RNA viruses such as Zika virus (ZIKV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
固有免疫力形成干细胞的病毒抗性。
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