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000179074 1001_ $$aMetz-Zumaran, Camila$$b0
000179074 245__ $$aIncreased Sensitivity of SARS-CoV-2 to Type III Interferon in Human Intestinal Epithelial Cells.
000179074 260__ $$aBaltimore, Md.$$bSoc.$$c2022
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000179074 500__ $$a#EA:F140#LA:F140# / 2022 Apr 13;96(7):e0170521
000179074 520__ $$aThe 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.
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000179074 650_7 $$2Other$$aSARS-CoV-2
000179074 650_7 $$2Other$$ahuman intestinal epithelial cells
000179074 650_7 $$2Other$$ainterferon
000179074 650_7 $$2Other$$ainterferon lambda
000179074 650_7 $$2Other$$aintrinsic immune response
000179074 650_7 $$2Other$$atype III interferon
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000179074 7001_ $$0P:(DE-He78)51c7e0db09353baf8fff5d9a63da0abb$$aDoldan, Patricio$$b2$$eFirst author$$udkfz
000179074 7001_ $$aGuo, Cuncai$$b3
000179074 7001_ $$0P:(DE-He78)8c3dd76230733f354d346a2fbe8db355$$aStanifer, Megan L$$b4$$udkfz
000179074 7001_ $$0P:(DE-He78)4658b59d5b4e54b919fc63ab1213c78f$$aBoulant, Steeve$$b5$$eLast author$$udkfz
000179074 773__ $$0PERI:(DE-600)1495529-5$$a10.1128/jvi.01705-21$$gp. e01705-21$$n7$$pe0170521$$tJournal of virology$$v96$$x0022-538X$$y2022
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