%0 Journal Article
%A Metz-Zumaran, Camila
%A Kee, Carmon
%A Doldan, Patricio
%A Guo, Cuncai
%A Stanifer, Megan L
%A Boulant, Steeve
%T Increased Sensitivity of SARS-CoV-2 to Type III Interferon in Human Intestinal Epithelial Cells.
%J Journal of virology
%V 96
%N 7
%@ 0022-538X
%C Baltimore, Md.
%I Soc.
%M DKFZ-2022-00450
%P e0170521
%D 2022
%Z #EA:F140#LA:F140# / 2022 Apr 13;96(7):e0170521
%X 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.
%K SARS-CoV-2 (Other)
%K human intestinal epithelial cells (Other)
%K interferon (Other)
%K interferon lambda (Other)
%K intrinsic immune response (Other)
%K type III interferon (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:35262371
%R 10.1128/jvi.01705-21
%U https://inrepo02.dkfz.de/record/179074