Zika virus (ZIKV) infection during pregnancy is associated with congenital brain abnormalities, a finding that highlights the urgent need to understand mother-to-fetus transmission mechanisms. Human umbilical cord mesenchymal stem cells (hUCMSCs) are susceptible to ZIKV infection but the underlying mechanisms of viral susceptibility remain largely unexplored. In this study, we have characterized and compared host mRNA and miRNA expression profiles in hUCMSCs after infection with two lineages of ZIKV, African (MR766) and Asian (PRVABC59). RNA sequencing analysis identified differentially expressed genes involved in anti-viral immunity and mitochondrial dynamics following ZIKV infection. In particular, ZIKV-infected hUCMSCs displayed mitochondrial elongation and the treatment of hUCMSCs with mitochondrial fission inhibitor led to a dose-dependent increase in ZIKV gene expression and decrease in anti-viral signalling pathways. Moreover, small RNA sequencing analysis identified several significantly up- or down-regulated microRNAs. Interestingly, miR-142-5p was significantly downregulated upon ZIKV infection, whereas cellular targets of miR-142-5p, IL6ST and ITGAV, were upregulated. Overexpression of miR-142-5p resulted in the suppression of ZIKV replication. Furthermore, blocking ITGAV expression resulted in a significant suppression of ZIKV binding to cells, suggesting a potential role of ITGAV in ZIKV entry. In conclusion, these results demonstrate both common and specific host responses to African and Asian ZIKV lineages and indicate miR-142-5p as a key regulator of ZIKV replication in the umbilical cords.

怀孕期间的寨卡病毒（ZIKV）感染与先天性大脑异常有关，这一发现突出表明了迫切需要了解母婴传播机制。人脐带间充质干细胞（hUCMSC）易受ZIKV感染，但病毒敏感性的基本机制仍未得到充分探索。在这项研究中，我们已经表征和比较了感染ZIKV的两个谱系，非洲（MR766）和亚洲（PRVABC59）的hUCMSC中的宿主mRNA和miRNA表达谱。RNA测序分析确定了ZIKV感染后参与抗病毒免疫和线粒体动力学的差异表达基因。尤其是，ZIKV感染的hUCMSCs表现出线粒体伸长，用线粒体裂变抑制剂处理hUCMSCs导致ZIKV基因表达呈剂量依赖性增加，而抗病毒信号通路减少。此外，小分子RNA测序分析确定了几种显着上调或下调的microRNA。有趣的是，在ZIKV感染后，miR-142-5p明显下调，而miR-142-5p的细胞靶标IL6ST和ITGAV上调。miR-142-5p的过表达导致ZIKV复制的抑制。此外，阻断ITGAV表达导致ZIKV与细胞结合的显着抑制，表明ITGAV在ZIKV进入中的潜在作用。总之，这些结果证明了宿主对非洲和亚洲ZIKV谱系的共同应答和特异性应答，并表明miR-142-5p是脐带ZIKV复制的关键调节因子。