Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium.

BioRxiv : the Preprint Server for Biology
Neal G. RavindraCraig B Wilen

Abstract

SARS-CoV-2, the causative agent of COVID-19, has tragically burdened individuals and institutions around the world. There are currently no approved drugs or vaccines for the treatment or prevention of COVID-19. Enhanced understanding of SARS-CoV-2 infection and pathogenesis is critical for the development of therapeutics. To reveal insight into viral replication, cell tropism, and host-viral interactions of SARS-CoV-2 we performed single-cell RNA sequencing of experimentally infected human bronchial epithelial cells (HBECs) in air-liquid interface cultures over a time-course. This revealed novel polyadenylated viral transcripts and highlighted ciliated cells as a major target of infection, which we confirmed by electron microscopy. Over the course of infection, 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 IFNs and IL6 but not IL1. This results in expression of interferon-stimulated genes in both infected and bystander cells. We observe similar gene expression changes from a COVID-19 patient ex vivo. In addition, we developed a new computational method termed CONditional DENSity Embedding (CONDENSE) to characte...Continue Reading

Citations

Jul 28, 2020·Molecular Systems Biology·Feria HikmetCecilia Lindskog
Oct 22, 2020·Science·Ludovico Cantuti-CastelvetriMikael Simons
Nov 10, 2020·ELife·Natalia Zamorano Cuervo, Nathalie Grandvaux
Nov 17, 2020·Frontiers in Cellular and Infection Microbiology·Giorgio BertolazziClaudia Coronnello
Jan 7, 2021·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Bhavesh D KevadiyaHoward E Gendelman
Jan 15, 2021·Clinical Microbiology Reviews·Aleksandra SynowiecKrzysztof Pyrc
Mar 7, 2021·International Journal of Molecular Sciences·Elvira ForteNadia A Rosenthal
Apr 9, 2021·Science Immunology·Bingyu YanMajid Kazemian
May 25, 2021·Frontiers in Medicine·Mirjam KienerMarianna Kruithof-de Julio
Feb 20, 2021·Annual Review of Pharmacology and Toxicology·Sareh PandamoozMohammad Saied Salehi

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Datasets Mentioned

BETA
MT020880.1

Methods Mentioned

BETA
scRNA-seq
Transmission
transmission electron microscopy
chip
PCR

Software Mentioned

GO
Python
Ensembl
bedtools intersect
UMAP
PANTHER
samtools
Scanpy

Related Concepts

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