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@ARTICLE{Doldan:181787,
author = {P. Doldan$^*$ and J. Dai and C. Metz-Zumaran and J. T.
Patton and M. L. Stanifer and S. Boulant$^*$},
title = {{T}ype {III} and {N}ot {T}ype {I} {I}nterferons
{E}fficiently {P}revent the {S}pread of {R}otavirus in
{H}uman {I}ntestinal {E}pithelial {C}ells.},
journal = {Journal of virology},
volume = {96},
number = {17},
issn = {0022-538X},
address = {Baltimore, Md.},
publisher = {Soc.},
reportid = {DKFZ-2022-02210},
pages = {e00706-22},
year = {2022},
note = {#EA:F140#LA:F140#},
abstract = {Rotavirus infects intestinal epithelial cells and is the
leading cause of gastroenteritis in infants worldwide. Upon
viral infection, intestinal cells produce type I and type
III interferons (IFNs) to alert the tissue and promote an
antiviral state. These two types of IFN bind to different
receptors but induce similar pathways that stimulate the
activation of interferon-stimulated genes (ISGs) to combat
viral infection. In this work, we studied the spread of a
fluorescent wild-type (WT) SA11 rotavirus in human
colorectal cancer cells lacking specific interferon
receptors and compared it to that of an NSP1 mutant
rotavirus that cannot interfere with the host intrinsic
innate immune response. We could show that the WT rotavirus
efficiently blocks the production of type I IFNs but that
type III IFNs are still produced, whereas the NSP1 mutant
rotavirus allows the production of both. Interestingly,
while both exogenously added type I and type III IFNs could
efficiently protect cells against rotavirus infection,
endogenous type III IFNs were found to be key to limit
infection of human intestinal cells by rotavirus. By using a
fluorescent reporter cell line to highlight the cells
mounting an antiviral program, we could show that paracrine
signaling driven by type III IFNs efficiently controls the
spread of both WT and NSP1 mutant rotavirus. Our results
strongly suggest that NSP1 efficiently blocks the type I
IFN-mediated antiviral response; however, its restriction of
the type III IFN-mediated one is not sufficient to prevent
type III IFNs from partially inhibiting viral spread in
intestinal epithelial cells. Additionally, our findings
further highlight the importance of type III IFNs in
controlling rotavirus infection, which could be exploited as
antiviral therapeutic measures. IMPORTANCE Rotavirus is one
of the most common causes of gastroenteritis worldwide. In
developing countries, rotavirus infections lead to more than
200,000 deaths in infants and children. The intestinal
epithelial cells lining the gastrointestinal tract combat
rotavirus infection by two key antiviral compounds known as
type I and III interferons. However, rotavirus has developed
countermeasures to block the antiviral actions of the
interferons. In this work, we evaluated the arms race
between rotavirus and type I and III interferons. We
determined that although rotavirus could block the induction
of type I interferons, it was unable to block type III
interferons. The ability of infected cells to produce and
release type III interferons leads to the protection of the
noninfected neighboring cells and the clearance of rotavirus
infection from the epithelium. This suggests that type III
interferons are key antiviral agents and could be used to
help control rotavirus infections in children.},
keywords = {Antiviral Agents: pharmacology / Child / Epithelial Cells /
Gastroenteritis: metabolism / Humans / Interferon Type I:
metabolism / Interferons: metabolism / Rotavirus: metabolism
/ Rotavirus Infections: metabolism / autocrine signaling
(Other) / human intestinal epithelial cells (Other) /
interferons (Other) / lambda interferon (IFN) (Other) /
paracrine signaling (Other) / rotavirus (Other) / rotavirus
NSP1 (Other) / type III interferon (IFN) (Other) / Antiviral
Agents (NLM Chemicals) / Interferon Type I (NLM Chemicals) /
Interferons (NLM Chemicals)},
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:36000839},
pmc = {pmc:PMC9472630},
doi = {10.1128/jvi.00706-22},
url = {https://inrepo02.dkfz.de/record/181787},
}