Epitranscriptomic m6A profile of SARS-CoV-2-infected human lung epithelial cells

NIH Pandemic-Era Grants

Pandemic Era Grants

2022

↗ Live URL (may be dead)

Document text

Principal Investigator: Li  Wu
Organization: UNIVERSITY OF IOWA
Fiscal Year: 2022
Award: $231,750
Funding agency: National Institute of Allergy and Infectious Diseases

Abstract
The COVID-19 pandemic caused by severe acute respiratory syndrome-related coronavirus 2
(SARS-CoV-2) has resulted in global health and economic crises. To develop effective vaccines
and antivirals to prevent and control SARS-CoV-2 or other coronavirus infections, it is critical to
understand the regulatory mechanisms of SARS-CoV-2 genome replication in host cells. In this
R21 project, we will use novel epitranscriptomic technologies to investigate SARS-CoV-2
replication in human lung epithelial cells. N6-methyladenosine (m6A) modifications of many
viruses play a major role in epitranscriptomic regulation of viral replication, gene expression, and
immune evasion. However, it is unclear whether and how m6A modifications of the SARS-CoV-2
genome and cellular genes affect viral replication and pathogenicity.
Our preliminary studies showed that SARS-CoV-2 infection of human lung epithelial cells
upregulated m6A levels in cellular RNA. Our bioinformatic analysis of 13,699 full-length SARS-
CoV-2 genome sequences predicts multiple m6A modification sites that are highly conserved
among SARS-CoV-2 isolates worldwide. Thus, we hypothesize that m6A modifications of the
SARS-CoV-2 genome and cellular genes enhance viral replication in cells through
epitranscriptomic regulation. We propose two specific aims to test this hypothesis. Aim 1. To
investigate the m6A epitranscriptomic profile of SARS-CoV-2-infected lung epithelial cells; Aim 2.
To map m6A sites on the SARS-CoV-2 genome and to identify critical sites for viral replication.
Defining epitranscriptomic m6A profile of SARS-CoV-2-infected cells has significant implications
in understanding the COVID-19 pathogenesis and identifying novel drug targets.

Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Address><Affect><Antiviral Agents><Antiviral Drugs><Antivirals><Attenuated><Bio-Informatics><Bioinformatics><COVID crisis><COVID epidemic><COVID pandemic><COVID-19><COVID-19 crisis><COVID-19 epidemic><COVID-19 genome><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 infection><COVID-19 pandemic><COVID-19 pathogenesis><COVID-19 public health crisis><COVID-19 therapy><COVID-19 treatment><COVID-19 virus><COVID-19 virus genome><COVID19><COVID19 crisis><COVID19 epidemic><COVID19 genome><COVID19 global health crisis><COVID19 global pandemic><COVID19 health crisis><COVID19 infection><COVID19 pandemic><COVID19 pathogenesis><COVID19 public health crisis><COVID19 therapy><COVID19 treatment><COVID19 virus><COVID19 virus genome><CV-19><CV19><Cell Body><Cells><Chemicals><Clinical><CoV-2><CoV2><Collaborations><Coronaviridae><Coronaviridae Infections><Coronavirus><Coronavirus Infections><Cytokine Gene><Data><Development><Drugs><Epithelial Cells><Foundations><Future><Gene Action Regulation><Gene Expression><Gene Expression Regulation><Gene Regulation><Gene Regulation Process><Genes><HIV-1><HIV-I><HIV1><Hour><Human><Human Immunodeficiency Virus Type 1><Human immunodeficiency virus 1><IFN><Immune Evasion><Immune Precipitation><Immunoprecipitation><Infection><Inflammatory><Interferon Type I><Interferons><Italy><Left><Length><Lung><Lung Respiratory System><Maps><Medication><Messenger RNA><Modern Man><Modification><Molecular><Non-Polyadenylated RNA><Nucleotides><Organism><Pathogenicity><Patients><Pharmaceutic Preparations><Pharmaceutical Preparations><Play><Post-Transcriptional Control><Post-Transcriptional Regulation><RNA><RNA Gene Products><RNA Seq><RNA sequencing><RNAseq><Regulation><Ribonucleic Acid><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 epidemic><SARS-CoV-2 genome><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 infection><SARS-CoV-2 pandemic><SARS-CoV-2 therapy><SARS-CoV-2 treatment><SARS-CoV2><SARS-CoV2 epidemic><SARS-CoV2 genome><SARS-CoV2 infection><SARS-CoV2 pandemic><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome related corona virus 2><Site><Technology><Testing><Vaccines><Viral Genes><Viral Genome><Viral Pathogenesis><Virus><Virus Replication><Wuhan coronavirus><anti-viral agents><anti-viral compound><anti-viral drugs><anti-viral medication><anti-viral therapeutic><anti-virals><antiviral compound><antiviral medication><antiviral therapeutic><base><cellular targeting><corona virus><corona virus disease 2019><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><coronavirus disease 2019><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 genome><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 infection><coronavirus disease 2019 pandemic><coronavirus disease 2019 pathogenesis><coronavirus disease 2019 public health crisis><coronavirus disease 2019 therapy><coronavirus disease 2019 treatment><coronavirus disease 2019 virus><coronavirus disease 2019 virus genome><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus disease-19 pathogenesis><coronavirus disease-19 virus><coronavirus infectious disease-19><cytokine><cytokine release syndrome><cytokine storm><developmental><drug/agent><epitranscriptomics><genomic RNA><global health><hCoV19><health economics><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><life-threatening COVID><life-threatening COVID-19><life-threatening SARS-CoV-2><life-threatening coronavirus disease><life-threatening coronavirus disease 2019><life-threatening severe acute respiratory syndrome coronavirus 2><living system><mRNA><mRNA Expression><mutant><nCoV2><new drug target><new druggable target><new pharmacotherapy target><new therapeutic target><new therapy target><novel><novel drug target><novel druggable target><novel pharmacotherapy target><novel therapeutic target><novel therapy target><post-transcriptional gene regulation><posttranscriptional control><posttranscriptional regulation><prevent><preventing><pulmonary><serious COVID><serious COVID-19><serious SARS-CoV-2><serious coronavirus disease><serious coronavirus disease 2019><serious severe acute respiratory syndrome coronavirus 2><severe COVID><severe COVID-19><severe COVID19><severe SARS-CoV-2><severe acute respiratory syndrome coronavirus 2 genome><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><severe acute respiratory syndrome coronavirus 2 therapy><severe acute respiratory syndrome coronavirus 2 treatment><severe coronavirus disease><severe coronavirus disease 19><severe coronavirus disease 2019><severe severe acute respiratory syndrome coronavirus 2><social role><therapeutically effective><transcriptome sequencing><treat COVID-19><treat COVID19><treat SARS-CoV-2><treat coronavirus disease 2019><treat severe acute respiratory syndrome coronavirus 2><vaccine candidate><viral multiplication><viral replication><virus genome><virus multiplication><virus pathogenesis>