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Betacoronaviruses SARS-CoV-2 and HCoV-OC43 infections in IGROV-1 cell line require aryl hydrocarbon receptor

Meisam Yousefi1, Wai Suet Lee1, Wharton O Y Chan1

  • 1Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.

Emerging Microbes & Infections
|September 6, 2023
PubMed

Insights

This study identifies IGROV-1 cells as a powerful tool for studying betacoronaviruses like SARS-CoV-2. These cells revealed Aryl hydrocarbon receptor (AHR) as a key factor for viral replication, aiding in the development of new antiviral strategies.

Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • Novel betacoronaviruses, including SARS-CoV-2, present substantial global health and economic challenges.
  • Effective diagnostic and research tools are crucial for managing and mitigating coronavirus outbreaks.

Purpose of the Study:

  • To characterize the human cell line IGROV-1 for its utility in detecting, propagating, and titrating betacoronaviruses.
  • To identify host factors essential for SARS-CoV-2 and HCoV-OC43 replication using IGROV-1 cells.
  • To evaluate the therapeutic potential of targeting identified host factors against betacoronavirus infections.

Main Methods:

  • Characterization of IGROV-1 cells for SARS-CoV-2 and HCoV-OC43 propagation and titration.
  • Time-course transcriptomics to analyze the innate immune response in infected IGROV-1 cells.
  • Genome-wide CRISPR knockout screens in IGROV-1 cells to identify host dependency factors.
  • Antiviral drug testing using a small molecule inhibitor of Aryl hydrocarbon receptor (AHR).

Main Results:

  • IGROV-1 cells demonstrated robust susceptibility to SARS-CoV-2 and HCoV-OC43, supporting viral replication and innate immune responses.
  • Aryl hydrocarbon receptor (AHR) was identified as a critical host dependency factor for both SARS-CoV-2 and HCoV-OC43.
  • The AHR inhibitor DiMNF selectively inhibited HCoV-OC43 infection, but not SARS-CoV-2, by modulating innate immune responses.

Conclusions:

  • IGROV-1 cells serve as a valuable and versatile tool for betacoronavirus research, including diagnostics, serological assays, and antiviral drug screening.
  • The identification of AHR as a host factor provides new avenues for developing targeted antiviral therapies against specific betacoronaviruses.
  • Findings underscore the importance of host-pathogen interactions in understanding viral pathogenesis and developing effective countermeasures.
Keywords:
AHRCOVID-19DiMNFGenome-scale CRISPR screeningHCoV-OC43IGROV-1SARS-CoV-2betacoronavirus

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