Center for Infection and Immunity Study, School of Medicine, Sun Yat-sen University, Shenzhen, China.
Front Cell Infect Microbiol. 2022 Jun 10;12:911313. doi: 10.3389/fcimb.2022.911313. eCollection 2022.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was initially described to target the respiratory system and now has been reported to infect a variety of cell types, including cardiomyocytes, neurons, hepatocytes, and gut enterocytes. However, it remains unclear whether the virus can directly infect human embryonic stem cells (hESCs) or early embryos. Herein, we sought to investigate this question in a cell-culture system of hESCs. Both the RNA and S protein of SARS-CoV-2 were detected in the infected hESCs and the formation of syncytium was observed. The increased level of subgenomic viral RNA and the presence of dsRNA indicate active replication of SARS-CoV-2 in hESCs. The increase of viral titers in the supernatants revealed virion release, further indicating the successful life cycle of SARS-CoV-2 in hESCs. Remarkably, immunofluorescence microscopy showed that only a small portion of hESCs were infected, which may reflect low expression of SARS-CoV-2 receptors. By setting |log2 (fold change)| > 0.5 as the threshold, a total of 1,566 genes were differentially expressed in SARS-CoV-2-infected hESCs, among which 17 interferon-stimulated genes (ISGs) were significantly upregulated. Altogether, our results provide novel evidence to support the ability of SARS-CoV-2 to infect and replicate in hESCs.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）最初被描述为靶向呼吸系统，现在已被报道感染多种细胞类型，包括心肌细胞、神经元、肝细胞和肠道肠细胞。然而，目前尚不清楚该病毒是否可以直接感染人类胚胎干细胞（hESCs）或早期胚胎。在此，我们试图在 hESCs 的细胞培养系统中研究这个问题。SARS-CoV-2 的 RNA 和 S 蛋白均在感染的 hESCs 中被检测到，并观察到合胞体的形成。亚基因组病毒 RNA 水平的增加和 dsRNA 的存在表明 SARS-CoV-2 在 hESCs 中复制活跃。上清液中病毒滴度的增加表明病毒粒子的释放，进一步表明 SARS-CoV-2 在 hESCs 中的成功生命周期。值得注意的是，免疫荧光显微镜显示只有一小部分 hESCs 被感染，这可能反映出 SARS-CoV-2 受体的低表达。通过将 |log2（fold change）|>0.5 作为阈值，SARS-CoV-2 感染的 hESCs 中有 1566 个基因差异表达，其中 17 个干扰素刺激基因（ISGs）显著上调。总之，我们的结果提供了新的证据，支持 SARS-CoV-2 感染和在 hESCs 中复制的能力。
