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Retroviral Infection of Murine Embryonic Stem Cell Derived Embryoid Body Cells for Analysis of Hematopoietic Differentiation
Published on: October 20, 2014
Evidence of Infection of Human Embryonic Stem Cells by SARS-CoV-2
Weijie Zeng1, Fan Xing1, Yanxi Ji1
1Center for Infection and Immunity Study, School of Medicine, Sun Yat-sen University, Shenzhen, China.
Abstract:
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.
Insights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect human embryonic stem cells (hESCs). The virus actively replicates within hESCs, demonstrating a successful life cycle and impacting gene expression.
Area of Science:
- Virology
- Stem Cell Biology
- Embryology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily targets the respiratory system but has been found in various cell types.
- The potential for SARS-CoV-2 to infect human embryonic stem cells (hESCs) and early embryos remains largely unexplored.
Purpose of the Study:
- To investigate the susceptibility of hESCs to SARS-CoV-2 infection in a cell-culture system.
- To determine if SARS-CoV-2 can replicate within hESCs and assess the cellular response.
Main Methods:
- Infection of hESCs with SARS-CoV-2 in vitro.
- Detection of viral RNA and S protein using molecular assays.
- Assessment of viral replication via subgenomic RNA levels and viral titers.
- Analysis of gene expression changes using transcriptomics.
Main Results:
- SARS-CoV-2 RNA and S protein were detected in infected hESCs, with syncytium formation observed.
- Evidence of active viral replication, including increased subgenomic RNA, dsRNA presence, and virion release.
- Differential gene expression analysis revealed 1,566 altered genes, including 17 upregulated interferon-stimulated genes (ISGs).
Conclusions:
- SARS-CoV-2 can infect and replicate within hESCs, completing its life cycle.
- The limited infection rate may be due to low expression of viral receptors on hESCs.
- SARS-CoV-2 infection induces an interferon response in hESCs, impacting cellular gene expression.
