TY  - JOUR
AU  - Klute, Susanne
AU  - Nchioua, Rayhane
AU  - Cordsmeier, Arne
AU  - Vishwakarma, Jyoti
AU  - Koepke, Lennart
AU  - Alshammary, Hala
AU  - Jung, Christoph
AU  - Hirschenberger, Maximilian
AU  - Hoenigsperger, Helene
AU  - Fischer, Jana-Romana
AU  - Sivarajan, Rinu
AU  - Zech, Fabian
AU  - Stenger, Steffen
AU  - Serra-Moreno, Ruth
AU  - Gonzalez-Reiche, Ana Silvia
AU  - Sordillo, Emilia Mia
AU  - van Bakel, Harm
AU  - Simon, Viviana
AU  - Kirchhoff, Frank
AU  - Jacob, Timo
AU  - Kmiec, Dorota
AU  - Pichlmair, Andreas
AU  - Ensser, Armin
AU  - Sparrer, Konstantin Maria Johannes
TI  - Mutation T9I in Envelope confers autophagy resistance to SARS-CoV-2 Omicron.
JO  - iScience
VL  - 28
IS  - 7
SN  - 2589-0042
CY  - St. Louis
PB  - Elsevier
M1  - DZNE-2025-00881
SP  - 112974
PY  - 2025
AB  - 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.
KW  - Biological sciences (Other)
KW  - Cell biology (Other)
KW  - Microbiology (Other)
KW  - Natural sciences (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40687831
C2  - pmc:PMC12272759
DO  - DOI:10.1016/j.isci.2025.112974
UR  - https://pub.dzne.de/record/280042
ER  -