Zika Virus Targets Different Primary Human Placental Cells, Suggesting Two Routes for Vertical Transmission.
Zika Virus Targets Different Primary Human Placental Cells, Suggesting Two Routes for Vertical Transmission.
复制标题
寨卡病毒靶向不同的原代人胎盘细胞，这表明垂直传播的两条途径。
DOI：
10.1016/j.chom.2016.07.002
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发表时间：
2016-08-10
影响因子：
30.3
通讯作者：
Pereira L
中科院分区：
文献类型：
--
作者：
Tabata T;Petitt M;Puerta-Guardo H;Michlmayr D;Wang C;Fang-Hoover J;Harris E;Pereira L
怀孕期间感染寨卡病毒（ZIKV）与严重的出生缺陷有关，但母婴传播途径尚不清楚。我们用原型乌干达病毒株和最近分离的尼加拉瓜 ZIKV 毒株感染了来自妊娠中期和晚期胎盘和妊娠早期绒毛膜绒毛外植体的不同原代细胞类型。 ZIKV 感染原代人胎盘细胞和外植体 - 绒毛膜绒毛和羊膜上皮细胞中的细胞滋养细胞、内皮细胞、成纤维细胞和 Hofbauer 细胞，以及表达 Axl、Tyro3 和/或 TIM1 病毒进入辅助因子的羊膜绒毛膜中的滋养层祖细胞。与妊娠晚期胎盘相比，ZIKV 产生 NS3 和 E 蛋白，并在妊娠中期的羊膜上皮细胞中产生更高的病毒滴度。耐久霉素是一种肽，可与包膜病毒粒子中的磷脂酰乙醇胺结合并阻止 TIM1 结合，从而减少胎盘细胞和外植体中的 ZIKV 感染。我们的结果表明，ZIKV 从基底和顶叶蜕膜传播到绒毛膜绒毛和羊膜绒毛膜，靶向 TIM1 可以抑制子宫胎盘界面的感染。寨卡病毒 (ZIKV) 在怀孕期间感染胎儿，导致毁灭性的出生缺陷。塔巴塔等人。显示 ZIKV 感染多种原代细胞类型和人类胎盘外植体，表明病毒传播的胎盘和胎盘旁途径。耐久霉素（ZIKV 辅因子 TIM1 的抑制剂）可阻断病毒感染。
Zika virus (ZIKV) infection during pregnancy is linked to severe birth defects, but mother-to-fetus transmission routes are unknown. We infected different primary cell types from mid- and late-gestation placentas and explants from first-trimester chorionic villi with the prototype Ugandan and a recently-isolated Nicaraguan ZIKV strain. ZIKV infects primary human placental cells and explants – cytotrophoblasts, endothelial cells, fibroblasts and Hofbauer cells in chorionic villi and amniotic epithelial cells, and trophoblast progenitors in amniochorionic membranes expressing Axl, Tyro3 and/or TIM1 viral entry cofactors. ZIKV produced NS3 and E proteins and generated higher viral titers in amniotic epithelial cells from mid-gestation compared to late-gestation placentas. Duramycin, a peptide that binds phosphatidylethanolamine in enveloped virions and precludes TIM1 binding, reduced ZIKV infection in placental cells and explants. Our results suggest that ZIKV spreads from basal and parietal decidua to chorionic villi and amniochorionic membranes, and targeting TIM1 could suppress infection at the uterine-placental interface. Zika virus (ZIKV) infects the fetus during pregnancy, causing devastating birth defects. Tabata et al. show that ZIKV infects numerous primary cell types and explants of the human placenta, suggesting placental and paraplacental routes of virus transmission. Virus infection is blocked by duramycin, an inhibitor of the ZIKV cofactor TIM1.