Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells.
Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells.
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DOI：
10.1038/s41467-017-02790-9
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发表时间：
2018-02-02
影响因子：
16.6
通讯作者：
Zatz M
中科院分区：
文献类型：
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作者：
Caires-Júnior LC;Goulart E;Melo US;Araujo BHS;Alvizi L;Soares-Schanoski A;de Oliveira DF;Kobayashi GS;Griesi-Oliveira K;Musso CM;Amaral MS;daSilva LF;Astray RM;Suárez-Patiño SF;Ventini DC;Gomes da Silva S;Yamamoto GL;Ezquina S;Naslavsky MS;Telles-Silva KA;Weinmann K;van der Linden V;van der Linden H;de Oliveira JRM;Arrais NMR;Melo A;Figueiredo T;Santos S;Meira JGC;Passos SD;de Almeida RP;Bispo AJB;Cavalheiro EA;Kalil J;Cunha-Neto E;Nakaya H;Andreata-Santos R;de Souza Ferreira LC;Verjovski-Almeida S;Ho PL;Passos-Bueno MR;Zatz M
先天性寨卡综合征（CZS）通过影响神经祖细胞（NPC）导致早期脑发育障碍。在这里，我们分析了NPC从三对异卵双胞胎不一致的CZS。我们通过RNA-Seq比较了来自受CCRs影响和未受CCRs影响的双胞胎的NPC。在寨卡病毒（ZIKV）感染之前，来自CZS婴儿的NPC显示出mTOR和Wnt通路调节剂的显著不同的基因表达特征，这是神经发育程序的关键。在ZIKV体外感染后，来自受影响个体的细胞具有显著更高的ZIKV复制和降低的细胞生长。在18个受影响的CZS婴儿相比，5个未受影响的双胞胎和609个对照组的全外显子组分析排除了一个单基因模型来解释抵抗或增加易感性CZS发展。总体而言，我们的研究结果表明，CZS不是一个随机事件，并依赖于NPC的内在易感性，可能与寡基因和/或表观遗传机制。寨卡病毒（ZIKV）感染可导致先天性寨卡综合征（CZS），但其潜在机制知之甚少。在这里，作者从具有关于CZS的不一致表型的双卵双胞胎中产生神经祖细胞，并研究它们对ZIKV感染的反应。
Congenital Zika syndrome (CZS) causes early brain development impairment by affecting neural progenitor cells (NPCs). Here, we analyze NPCs from three pairs of dizygotic twins discordant for CZS. We compare by RNA-Seq the NPCs derived from CZS-affected and CZS-unaffected twins. Prior to Zika virus (ZIKV) infection the NPCs from CZS babies show a significantly different gene expression signature of mTOR and Wnt pathway regulators, key to a neurodevelopmental program. Following ZIKV in vitro infection, cells from affected individuals have significantly higher ZIKV replication and reduced cell growth. Whole-exome analysis in 18 affected CZS babies as compared to 5 unaffected twins and 609 controls excludes a monogenic model to explain resistance or increased susceptibility to CZS development. Overall, our results indicate that CZS is not a stochastic event and depends on NPC intrinsic susceptibility, possibly related to oligogenic and/or epigenetic mechanisms. Zika virus (ZIKV) infection can cause congenital Zika syndrome (CZS), but the underlying mechanisms are poorly understood. Here, the authors generate neural progenitor cells from dizygotic twins with a discordant phenotype regarding CZS and study their response to ZIKV infection.
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DOI：
10.1126/science.aaf5036
发表时间：
2016-04-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Faria NR;Azevedo RDSDS;Kraemer MUG;Souza R;Cunha MS;Hill SC;Thézé J;Bonsall MB;Bowden TA;Rissanen I;Rocco IM;Nogueira JS;Maeda AY;Vasami FGDS;Macedo FLL;Suzuki A;Rodrigues SG;Cruz ACR;Nunes BT;Medeiros DBA;Rodrigues DSG;Queiroz ALN;da Silva EVP;Henriques DF;da Rosa EST;de Oliveira CS;Martins LC;Vasconcelos HB;Casseb LMN;Simith DB;Messina JP;Abade L;Lourenço J;Alcantara LCJ;de Lima MM;Giovanetti M;Hay SI;de Oliveira RS;Lemos PDS;de Oliveira LF;de Lima CPS;da Silva SP;de Vasconcelos JM;Franco L;Cardoso JF;Vianez-Júnior JLDSG;Mir D;Bello G;Delatorre E;Khan K;Creatore M;Coelho GE;de Oliveira WK;Tesh R;Pybus OG;Nunes MRT;Vasconcelos PFC
通讯作者：
Vasconcelos PFC
FOXG1 综合征的核心表型包括出生后小头畸形、严重智力低下、语言缺失、运动障碍和胼胝体发育不全。
影响因子：
4
作者：
Kortüm F;Das S;Flindt M;Morris-Rosendahl DJ;Stefanova I;Goldstein A;Horn D;Klopocki E;Kluger G;Martin P;Rauch A;Roumer A;Saitta S;Walsh LE;Wieczorek D;Uyanik G;Kutsche K;Dobyns WB
通讯作者：
Dobyns WB
影响因子：
6.7
作者：
Joubert PE;Stapleford K;Guivel-Benhassine F;Vignuzzi M;Schwartz O;Albert ML
通讯作者：
Albert ML
影响因子：
168.9
作者：
Franca, Giovanny V. A.;Schuler-Faccini, Lavinia;Victora, Cesar G.
通讯作者：
Victora, Cesar G.
影响因子：
8
作者：
Barbier, Alexandre;Boivin, Ariane;Nuyt, Anne Monique
通讯作者：
Nuyt, Anne Monique