Emerging Microbes and Infections (Dec 2023)

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

  • Meisam Yousefi,
  • Wai Suet Lee,
  • Wharton O. Y. Chan,
  • Wei He,
  • Marcus G. Mah,
  • Cythia Lingli Yong,
  • Joshua M. Deerain,
  • Lijin Wang,
  • Camille Arcinas,
  • Biaoguo Yan,
  • Dewei Tan,
  • Wan Rong Sia,
  • Akshamal M. Gamage,
  • Jinxuan Yang,
  • Alan Chen-Yu Hsu,
  • Shang Li,
  • Martin Linster,
  • Xinglou Yang,
  • Sujoy Ghosh,
  • Danielle E. Anderson,
  • Gavin J. D. Smith,
  • Chee Wah Tan,
  • Lin-Fa Wang,
  • Yaw Shin Ooi

DOI
https://doi.org/10.1080/22221751.2023.2256416
Journal volume & issue
Vol. 12, no. 2

Abstract

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The emergence of novel betacoronaviruses has posed significant financial and human health burdens, necessitating the development of appropriate tools to combat future outbreaks. In this study, we have characterized a human cell line, IGROV-1, as a robust tool to detect, propagate, and titrate betacoronaviruses SARS-CoV-2 and HCoV-OC43. IGROV-1 cells can be used for serological assays, antiviral drug testing, and isolating SARS-CoV-2 variants from patient samples. Using time-course transcriptomics, we confirmed that IGROV-1 cells exhibit a robust innate immune response upon SARS-CoV-2 infection, recapitulating the response previously observed in primary human nasal epithelial cells. We performed genome-wide CRISPR knockout genetic screens in IGROV-1 cells and identified Aryl hydrocarbon receptor (AHR) as a critical host dependency factor for both SARS-CoV-2 and HCoV-OC43. Using DiMNF, a small molecule inhibitor of AHR, we observed that the drug selectively inhibits HCoV-OC43 infection but not SARS-CoV-2. Transcriptomic analysis in primary normal human bronchial epithelial cells revealed that DiMNF blocks HCoV-OC43 infection via basal activation of innate immune responses. Our findings highlight the potential of IGROV-1 cells as a valuable diagnostic and research tool to combat betacoronavirus diseases.

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