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@ARTICLE{MetzZumaran:179074,
author = {C. Metz-Zumaran and C. Kee$^*$ and P. Doldan$^*$ and C. Guo
and M. L. Stanifer and S. Boulant$^*$},
title = {{I}ncreased {S}ensitivity of {SARS}-{C}o{V}-2 to {T}ype
{III} {I}nterferon in {H}uman {I}ntestinal {E}pithelial
{C}ells.},
journal = {Journal of virology},
volume = {96},
number = {7},
issn = {0022-538X},
address = {Baltimore, Md.},
publisher = {Soc.},
reportid = {DKFZ-2022-00450},
pages = {e0170521},
year = {2022},
note = {#EA:F140#LA:F140# / 2022 Apr 13;96(7):e0170521},
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.},
keywords = {SARS-CoV-2 (Other) / human intestinal epithelial cells
(Other) / interferon (Other) / interferon lambda (Other) /
intrinsic immune response (Other) / type III interferon
(Other)},
cin = {F140},
ddc = {610},
cid = {I:(DE-He78)F140-20160331},
pnm = {316 - Infektionen, Entzündung und Krebs (POF4-316)},
pid = {G:(DE-HGF)POF4-316},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35262371},
doi = {10.1128/jvi.01705-21},
url = {https://inrepo02.dkfz.de/record/179074},
}