TY  - JOUR
AU  - Metz-Zumaran, Camila
AU  - Kee, Carmon
AU  - Doldan, Patricio
AU  - Guo, Cuncai
AU  - Stanifer, Megan L
AU  - Boulant, Steeve
TI  - Increased Sensitivity of SARS-CoV-2 to Type III Interferon in Human Intestinal Epithelial Cells.
JO  - Journal of virology
VL  - 96
IS  - 7
SN  - 0022-538X
CY  - Baltimore, Md.
PB  - Soc.
M1  - DKFZ-2022-00450
SP  - e0170521
PY  - 2022
N1  - #EA:F140#LA:F140# / 2022 Apr 13;96(7):e0170521
AB  - 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.
KW  - SARS-CoV-2 (Other)
KW  - human intestinal epithelial cells (Other)
KW  - interferon (Other)
KW  - interferon lambda (Other)
KW  - intrinsic immune response (Other)
KW  - type III interferon (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:35262371
DO  - DOI:10.1128/jvi.01705-21
UR  - https://inrepo02.dkfz.de/record/179074
ER  -