Increased sensitivity of SARS-CoV-2 to type III interferon in human intestinal epithelial cells

• Verfasst von: Metz Zumarán, Camila [VerfasserIn]
• Verfasst von: Kee, Carmon [VerfasserIn]
• Verfasst von: Doldan, Patricio [VerfasserIn]
• Verfasst von: Guo, Cuncai [VerfasserIn]
• Verfasst von: Stanifer, Megan [VerfasserIn]
• Verfasst von: Boulant, Steeve [VerfasserIn]
• Titel: Increased sensitivity of SARS-CoV-2 to type III interferon in human intestinal epithelial cells
• Verf.angabe: Camila Metz-Zumaran, Carmon Kee, Patricio Doldan, Cuncai Guo, Megan L. Stanifer, Steeve Boulant
• E-Jahr: 2022
• Jahr: 9 March 2022
• Umfang: 24 S.
• Fussnoten: Gesehen am 25.05.2022
• Titel Quelle: Enthalten in: Journal of virology
• Ort Quelle: Baltimore, Md. : Soc., 1967
• Jahr Quelle: 2022
• Band/Heft Quelle: 96(2022), 7, Artikel-ID e01705-21, Seite 1-24
• ISSN Quelle: 1098-5514
• DOI: doi:10.1128/jvi.01705-21
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1801827389

Abstract

The coronavirus SARS-CoV-2 caused the COVID-19 global pandemic leading to 5.3 million deaths worldwide as of December 2021. The human intestine was found to be a major viral target which could have a strong impact on virus spread and pathogenesis since it is one of the largest organs. While type I interferons (IFNs) are key cytokines acting against systemic virus spread, in the human intestine type III IFNs play a major role by restricting virus infection and dissemination without disturbing homeostasis. Recent studies showed that both type I and III IFNs can inhibit SARS-CoV-2 infection, but it is not clear whether one IFN controls SARS-CoV-2 infection of the human intestine better or with a faster kinetics. In this study, we could show that type I and III IFNs both possess antiviral activity against SARS-CoV-2 in human intestinal epithelial cells (hIECs); however, type III IFN is more potent. Shorter type III IFN pretreatment times and lower concentrations were required to efficiently reduce virus load compared to type I IFNs. Moreover, type III IFNs significantly inhibited SARS-CoV-2 even 4 h postinfection and induced a long-lasting antiviral effect in hIECs. Importantly, the sensitivity of SARS-CoV-2 to type III IFNs was virus specific since type III IFN did not control VSV infection as efficiently. Together, these results suggest that type III IFNs have a higher potential for IFN-based treatment of SARS-CoV-2 intestinal infection compared to type I IFNs., IMPORTANCE SARS-CoV-2 infection is not restricted to the respiratory tract and a large number of COVID-19 patients experience gastrointestinal distress. Interferons are key molecules produced by the cell to combat virus infection. Here, we evaluated how two types of interferons (type I and III) can combat SARS-CoV-2 infection of human gut cells. We found that type III interferons were crucial to control SARS-CoV-2 infection when added both before and after infection. Importantly, type III interferons were also able to produce a long-lasting effect, as cells were protected from SARS-CoV-2 infection up to 72 h posttreatment. This study suggested an alternative treatment possibility for SARS-CoV-2 infection.