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Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization
Published on: December 23, 2020
Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells,
Neal G Ravindra1,2, Mia Madel Alfajaro3,4, Victor Gasque1,2,5,6
1Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School Medicine, New Haven, Connecticut, United States of America.
Abstract:
There are currently limited Food and Drug Administration (FDA)-approved drugs and vaccines for the treatment or prevention of Coronavirus Disease 2019 (COVID-19). Enhanced understanding of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and pathogenesis is critical for the development of therapeutics. To provide insight into viral replication, cell tropism, and host-viral interactions of SARS-CoV-2, we performed single-cell (sc) RNA sequencing (RNA-seq) of experimentally infected human bronchial epithelial cells (HBECs) in air-liquid interface (ALI) cultures over a time course. This revealed novel polyadenylated viral transcripts and highlighted ciliated cells as a major target at the onset of infection, which we confirmed by electron and immunofluorescence microscopy. Over the course of infection, the cell tropism of SARS-CoV-2 expands to other epithelial cell types including basal and club cells. Infection induces cell-intrinsic expression of type I and type III interferons (IFNs) and interleukin (IL)-6 but not IL-1. This results in expression of interferon-stimulated genes (ISGs) in both infected and bystander cells. This provides a detailed characterization of genes, cell types, and cell state changes associated with SARS-CoV-2 infection in the human airway.
Insights
Researchers studied Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in human airway cells. Ciliated cells are an early target, with infection spreading to other cell types and triggering immune responses.
Area of Science:
- Cell Biology
- Virology
- Immunology
Background:
- Limited FDA-approved therapeutics exist for COVID-19.
- Understanding SARS-CoV-2 pathogenesis is crucial for drug development.
Purpose of the Study:
- Investigate viral replication, cell tropism, and host-viral interactions of SARS-CoV-2.
- Characterize host responses in the human airway during infection.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) of human bronchial epithelial cells (HBECs) in air-liquid interface (ALI) cultures over time.
- Electron microscopy and immunofluorescence microscopy to confirm cell tropism.
Main Results:
- Identified novel polyadenylated viral transcripts.
- Ciliated cells are an initial target, followed by basal and club cells.
- SARS-CoV-2 infection induces type I/III interferons and IL-6, leading to interferon-stimulated gene (ISG) expression in infected and bystander cells.
Conclusions:
- Detailed characterization of gene expression, cell types, and cell state changes during SARS-CoV-2 infection in the human airway.
- Provides insights into host-viral interactions and potential therapeutic targets.
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