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@ARTICLE{Klute:280042,
author = {Klute, Susanne and Nchioua, Rayhane and Cordsmeier, Arne
and Vishwakarma, Jyoti and Koepke, Lennart and Alshammary,
Hala and Jung, Christoph and Hirschenberger, Maximilian and
Hoenigsperger, Helene and Fischer, Jana-Romana and
Sivarajan, Rinu and Zech, Fabian and Stenger, Steffen and
Serra-Moreno, Ruth and Gonzalez-Reiche, Ana Silvia and
Sordillo, Emilia Mia and van Bakel, Harm and Simon, Viviana
and Kirchhoff, Frank and Jacob, Timo and Kmiec, Dorota and
Pichlmair, Andreas and Ensser, Armin and Sparrer, Konstantin
Maria Johannes},
title = {{M}utation {T}9{I} in {E}nvelope confers autophagy
resistance to {SARS}-{C}o{V}-2 {O}micron.},
journal = {iScience},
volume = {28},
number = {7},
issn = {2589-0042},
address = {St. Louis},
publisher = {Elsevier},
reportid = {DZNE-2025-00881},
pages = {112974},
year = {2025},
abstract = {Omicron has emerged as the most successful variant of
SARS-CoV-2. In addition to mutations in Spike that mediate
humoral immune escape, the Omicron-specific Envelope (E) T9I
mutation has been associated with increased transmission
fitness. However, the underlying mechanism remained unclear.
Here, we demonstrate that the E T9I mutation confers
resistance to autophagy. Rare Omicron patient isolates
encoding the ancestral E T9 remain sensitive to autophagy.
Conversely, introducing the E T9I mutation in recombinant
2020 SARS-CoV-2 renders it resistant to autophagy. Our data
indicate that the E T9I mutation protects virions against
lysosomal degradation. At the molecular level, the T9I
mutation increases the localization of E at autophagic
vesicles and promotes interaction with autophagy-associated
proteins SNX12, STX12, TMEM87B, and ABCG2. Our results show
that the E T9I mutation renders incoming virions resistant
to autophagy, suggesting that evasion of this antiviral
mechanism contributes to the efficient spread of Omicron.},
keywords = {Biological sciences (Other) / Cell biology (Other) /
Microbiology (Other) / Natural sciences (Other)},
cin = {AG Sparrer},
ddc = {050},
cid = {I:(DE-2719)1910003},
pnm = {351 - Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40687831},
pmc = {pmc:PMC12272759},
doi = {10.1016/j.isci.2025.112974},
url = {https://pub.dzne.de/record/280042},
}