Betacoronaviruses SARS-CoV-2 and HCoV-OC43 infections in IGROV-1 cell line require aryl hydrocarbon receptor
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Emerging microbes & infections - 12(2023), 2 vom: 06. Dez., Seite 2256416 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yousefi, Meisam [VerfasserIn] |
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| Links: |
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| Themen: |
AHR |
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| Anmerkungen: |
Date Completed 20.09.2023 Date Revised 03.10.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/22221751.2023.2256416 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM361701632 |
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| 245 | 1 | 0 | |a Betacoronaviruses SARS-CoV-2 and HCoV-OC43 infections in IGROV-1 cell line require aryl hydrocarbon receptor |
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| 500 | |a Date Revised 03.10.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a DiMNF | |
| 650 | 4 | |a Genome-scale CRISPR screening | |
| 650 | 4 | |a HCoV-OC43 | |
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| 650 | 4 | |a betacoronavirus | |
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| 700 | 1 | |a Lee, Wai Suet |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Wharton O Y |e verfasserin |4 aut | |
| 700 | 1 | |a He, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Mah, Marcus G |e verfasserin |4 aut | |
| 700 | 1 | |a Yong, Cythia Lingli |e verfasserin |4 aut | |
| 700 | 1 | |a Deerain, Joshua M |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Lijin |e verfasserin |4 aut | |
| 700 | 1 | |a Arcinas, Camille |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Biaoguo |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Dewei |e verfasserin |4 aut | |
| 700 | 1 | |a Sia, Wan Rong |e verfasserin |4 aut | |
| 700 | 1 | |a Gamage, Akshamal M |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Jinxuan |e verfasserin |4 aut | |
| 700 | 1 | |a Hsu, Alan Chen-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Shang |e verfasserin |4 aut | |
| 700 | 1 | |a Linster, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Xinglou |e verfasserin |4 aut | |
| 700 | 1 | |a Ghosh, Sujoy |e verfasserin |4 aut | |
| 700 | 1 | |a Anderson, Danielle E |e verfasserin |4 aut | |
| 700 | 1 | |a Smith, Gavin J D |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Chee Wah |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Lin-Fa |e verfasserin |4 aut | |
| 700 | 1 | |a Ooi, Yaw Shin |e verfasserin |4 aut | |
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