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叶酸对免疫功能低下小鼠寨卡病毒相关不良妊娠结局的预防作用。

Preventive effects of folic acid on Zika virus-associated poor pregnancy outcomes in immunocompromised mice.

机构信息

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

Graduate Institute of Microbiology and Public Health, College of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan.

出版信息

PLoS Pathog. 2020 May 11;16(5):e1008521. doi: 10.1371/journal.ppat.1008521. eCollection 2020 May.

DOI:10.1371/journal.ppat.1008521
PMID:32392268
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7241851/
Abstract

Zika virus (ZIKV) infection may lead to congenital microcephaly and pregnancy loss in pregnant women. In the context of pregnancy, folic acid (FA) supplementation may reduce the risk of abnormal pregnancy outcomes. Intriguingly, FA may have a beneficial effect on the adverse pregnancy outcomes associated with ZIKV infection. Here, we show that FA inhibits ZIKV replication in human umbilical vein endothelial cells (HUVECs) and a cell culture model of blood-placental barrier (BPB). The inhibitory effect of FA against ZIKV infection is associated with FRα-AMPK signaling. Furthermore, treatment with FA reduces pathological features in the placenta, number of fetal resorptions, and stillbirths in two mouse models of in utero ZIKV transmission. Mice with FA treatment showed lower viral burden and better prognostic profiles in the placenta including reduced inflammatory response, and enhanced integrity of BPB. Overall, our findings suggest the preventive role of FA supplementation in ZIKV-associated abnormal pregnancy and warrant nutritional surveillance to evaluate maternal FA status in areas with active ZIKV transmission.

摘要

寨卡病毒（ZIKV）感染可能导致孕妇先天性小头畸形和妊娠丢失。在妊娠期间，叶酸（FA）补充可能降低异常妊娠结局的风险。有趣的是，FA 可能对寨卡病毒感染相关的不良妊娠结局有有益的影响。在这里，我们表明 FA 抑制人脐静脉内皮细胞（HUVEC）和血胎盘屏障（BPB）的细胞培养模型中的 ZIKV 复制。FA 对 ZIKV 感染的抑制作用与 FRα-AMPK 信号有关。此外，FA 治疗可降低两种体内 ZIKV 传播的小鼠模型中的胎盘病理特征、胎儿吸收率和死产率。FA 治疗的小鼠在胎盘中的病毒载量更低，预后更好，包括炎症反应减少和 BPB 完整性增强。总体而言，我们的研究结果表明 FA 补充在寨卡病毒相关异常妊娠中的预防作用，并需要进行营养监测以评估具有活跃 ZIKV 传播地区的母体 FA 状态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341c/7241851/ff368db6d98a/ppat.1008521.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341c/7241851/7d266e050ebb/ppat.1008521.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341c/7241851/4bdec8b355a3/ppat.1008521.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341c/7241851/69a0d15187b8/ppat.1008521.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341c/7241851/c35958ba36e5/ppat.1008521.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341c/7241851/48ec57443517/ppat.1008521.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341c/7241851/180653edcfa5/ppat.1008521.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341c/7241851/ff368db6d98a/ppat.1008521.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341c/7241851/7d266e050ebb/ppat.1008521.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341c/7241851/4bdec8b355a3/ppat.1008521.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341c/7241851/69a0d15187b8/ppat.1008521.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341c/7241851/c35958ba36e5/ppat.1008521.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341c/7241851/48ec57443517/ppat.1008521.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341c/7241851/180653edcfa5/ppat.1008521.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341c/7241851/ff368db6d98a/ppat.1008521.g007.jpg

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