Differential Susceptibility of Fetal Retinal Pigment Epithelial Cells, hiPSC- Retinal Stem Cells, and Retinal Organoids to Zika Virus Infection.
Differential Susceptibility of Fetal Retinal Pigment Epithelial Cells, hiPSC- Retinal Stem Cells, and Retinal Organoids to Zika Virus Infection.
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DOI：
10.3390/v15010142
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发表时间：
2023-01-01
期刊：
影响因子：
--
通讯作者：
Arumugaswami V
中科院分区：
文献类型：
--
作者：
Contreras D;Garcia G Jr;Jones MK;Martinez LE;Jayakarunakaran A;Gangalapudi V;Tang J;Wu Y;Zhao JJ;Chen Z;Ramaiah A;Tsui I;Kumar A;Nielsen-Saines K;Wang S;Arumugaswami V
寨卡病毒（ZIKV）可导致小头畸形和先天性眼病。先天性ZIKV感染的细胞和分子基础尚未完全了解。在这里，我们利用人胎儿视网膜色素上皮细胞（FRPE）、hiPSC衍生的视网膜干细胞（iRSC）和视网膜类器官的生物学相关的基于细胞的系统来研究ZIKV介导的眼细胞损伤过程。我们的数据显示，FRPE对ZIKV感染高度敏感，表现出细胞凋亡增加，而iRSC显示出易感性降低。对感染的FRPE进行了详细的转录组学和蛋白质组学分析。核苷类似物药物治疗抑制ZIKV复制。视网膜类器官易受ZIKV感染。亚洲基因型ZIKV表现出更高的感染性，诱导严重的炎症反应，以及参与视网膜类器官分化的转录因子失调。总的来说，我们的研究表明，ZIKV影响不同发育阶段的眼细胞，导致细胞损伤和死亡，进一步提供了对先天性眼病发病机制的分子见解。
Zika virus (ZIKV) causes microcephaly and congenital eye disease. The cellular and molecular basis of congenital ZIKV infection are not well understood. Here, we utilized a biologically relevant cell-based system of human fetal retinal pigment epithelial cells (FRPEs), hiPSC-derived retinal stem cells (iRSCs), and retinal organoids to investigate ZIKV-mediated ocular cell injury processes. Our data show that FRPEs were highly susceptible to ZIKV infection exhibiting increased apoptosis, whereas iRSCs showed reduced susceptibility. Detailed transcriptomics and proteomics analyses of infected FRPEs were performed. Nucleoside analogue drug treatment inhibited ZIKV replication. Retinal organoids were susceptible to ZIKV infection. The Asian genotype ZIKV exhibited higher infectivity, induced profound inflammatory response, and dysregulated transcription factors involved in retinal organoid differentiation. Collectively, our study shows that ZIKV affects ocular cells at different developmental stages resulting in cellular injury and death, further providing molecular insight into the pathogenesis of congenital eye disease.
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影响因子：
3.4
作者：
Deutsch, Eric W.;Mendoza, Luis;Shteynberg, David;Farrah, Terry;Lam, Henry;Tasman, Natalie;Sun, Zhi;Nilsson, Erik;Pratt, Brian;Prazen, Bryan;Eng, Jimmy K.;Martin, Daniel B.;Nesvizhskii, Alexey I.;Aebersold, Ruedi
通讯作者：
Aebersold, Ruedi
影响因子：
1.9
作者：
Kovach JL;Schwartz SG;Flynn HW Jr;Scott IU
通讯作者：
Scott IU
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：
8
作者：
Jurado, Kellie Ann;Simoni, Michael K.;Fikrig, Erol
通讯作者：
Fikrig, Erol
DOI：
10.1111/jth.12178
发表时间：
2013-05
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
--
作者：
Hottz ED;Oliveira MF;Nunes PC;Nogueira RM;Valls-de-Souza R;Da Poian AT;Weyrich AS;Zimmerman GA;Bozza PT;Bozza FA
通讯作者：
Bozza FA