The Zika Virus Capsid Disrupts Corticogenesis by Suppressing Dicer Activity and miRNA Biogenesis.
The Zika Virus Capsid Disrupts Corticogenesis by Suppressing Dicer Activity and miRNA Biogenesis.
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寨卡病毒衣壳通过抑制 Dicer 活性和 miRNA 生物发生来破坏皮质生成
DOI：
10.1016/j.stem.2020.07.012
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发表时间：
2020-10-01
期刊：
影响因子：
23.9
通讯作者：
Liang Q
中科院分区：
文献类型：
--
作者：
Zeng J;Dong S;Luo Z;Xie X;Fu B;Li P;Liu C;Yang X;Chen Y;Wang X;Liu Z;Wu J;Yan Y;Wang F;Chen JF;Zhang J;Long G;Goldman SA;Li S;Zhao Z;Liang Q
寨卡病毒（ZIKV）可导致小头畸形并破坏神经发生。Dicer介导的miRNA生物发生是胚胎脑发育所需的，并且已经表明在ZIKV感染后被破坏。在这里，我们绘制了神经干细胞（NSC）中的ZIKV-宿主相互作用组，并发现Dicer被来自ZIKV的衣壳特异性靶向，而不是其他黄病毒，以促进ZIKV感染。我们鉴定了一种失去这种相互作用并且不抑制Dicer活性的衣壳突变体（H41 R）。一致地，ZIKV-H41 R毒性较低，并且不抑制体外神经发生或子宫内皮质发生。流行性ZIKV毒株含有增加Dicer结合亲和力并增强致病性的衣壳突变。ZIKV感染的NSC显示miRNA产生的整体抑制，包括与神经发生相关的关键miRNA，这在ZIKV-H41 R感染后没有观察到。这些发现一起表明，Dicer的caplase依赖性抑制是ZIKV免疫逃避和发病机制的主要决定因素，并且可能是ZIKV相关小头畸形的基础。Zeng等人评估了NSC中的ZIKV-宿主相互作用组，并发现ZIKV衣壳特异性结合并抑制Dicer以限制宿主miRNA生物合成，而其他黄病毒则不。Captain依赖性Dicer抑制决定ZIKV免疫逃避和发病机制，暗示ZIKV进化过程中致病活性的获得。
Zika virus (ZIKV) causes microcephaly and disrupts neurogenesis. Dicer-mediated miRNA biogenesis is required for embryonic brain development and has been suggested to be disrupted upon ZIKV infection. Here we mapped the ZIKV-host interactome in neural stem cells (NSCs) and found that Dicer is specifically targeted by the capsid from ZIKV, but not other flaviviruses, to facilitate ZIKV infection. We identified a capsid mutant (H41R) that loses this interaction and does not suppress Dicer activity. Consistently, ZIKV-H41R is less virulent and does not inhibit neurogenesis in vitro or corticogenesis in utero. Epidemic ZIKV strains contain capsid mutations that increase Dicer binding affinity and enhance pathogenicity. ZIKV-infected NSCs show global dampening of miRNA production, including key miRNAs linked to neurogenesis, that is not observed after ZIKV-H41R infection. Together these finding show that capsid-dependent suppression of Dicer is a major determinant of ZIKV immune evasion and pathogenesis, and may underlie ZIKV-related microcephaly. Zeng et al. assess the ZIKV-host interactome in NSCs and find the ZIKV capsid specifically binds and inhibits Dicer to limit host miRNA biogenesis, while other flaviviruses do not. Capsid-dependent Dicer suppression determines ZIKV immune evasion and pathogenesis, with implications for gain of pathogenic activity during ZIKV evolution.
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DOI：
10.3390/v9100297
发表时间：
2017-10-14
期刊：
Viruses
影响因子：
--
作者：
Kozak RA;Majer A;Biondi MJ;Medina SJ;Goneau LW;Sajesh BV;Slota JA;Zubach V;Severini A;Safronetz D;Hiebert SL;Beniac DR;Booth TF;Booth SA;Kobinger GP
通讯作者：
Kobinger GP
影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
DOI：
10.1056/nejmoa1602412
发表时间：
2016-12-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brasil P;Pereira JP Jr;Moreira ME;Ribeiro Nogueira RM;Damasceno L;Wakimoto M;Rabello RS;Valderramos SG;Halai UA;Salles TS;Zin AA;Horovitz D;Daltro P;Boechat M;Raja Gabaglia C;Carvalho de Sequeira P;Pilotto JH;Medialdea-Carrera R;Cotrim da Cunha D;Abreu de Carvalho LM;Pone M;Machado Siqueira A;Calvet GA;Rodrigues Baião AE;Neves ES;Nassar de Carvalho PR;Hasue RH;Marschik PB;Einspieler C;Janzen C;Cherry JD;Bispo de Filippis AM;Nielsen-Saines K
通讯作者：
Nielsen-Saines K
影响因子：
5.3
作者：
Davis, Tigwa H.;Cuellar, Trinna L.;Ullian, Erik M.
通讯作者：
Ullian, Erik M.
DOI：
10.1126/science.1190809
发表时间：
2010-06-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cifuentes D;Xue H;Taylor DW;Patnode H;Mishima Y;Cheloufi S;Ma E;Mane S;Hannon GJ;Lawson ND;Wolfe SA;Giraldez AJ
通讯作者：
Giraldez AJ