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

posted on 2023-09-19, 01:41 authored by 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

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.


CWT is funded by the Ministry of Health of Singapore [MOH-000535/MOH-OFYIRG19nov-0002]. LFW is supported by the Ministry of Health of Singapore [MOH-000505-02 and COVID19RF-001]. YSO is supported by Duke-NUS Medical School [Pilot Grant Duke/Duke-NUS/RECA(Pilot)/2019/0047], National Research Foundation of Singapore [NRF-MOST Joint Grant (MOH-000928)], and the Ministry of Education of Singapore [MOE-000095-01].