%0 Journal Article
%A Klute, Susanne
%A Nchioua, Rayhane
%A Cordsmeier, Arne
%A Vishwakarma, Jyoti
%A Koepke, Lennart
%A Alshammary, Hala
%A Jung, Christoph
%A Hirschenberger, Maximilian
%A Hoenigsperger, Helene
%A Fischer, Jana-Romana
%A Sivarajan, Rinu
%A Zech, Fabian
%A Stenger, Steffen
%A Serra-Moreno, Ruth
%A Gonzalez-Reiche, Ana Silvia
%A Sordillo, Emilia Mia
%A van Bakel, Harm
%A Simon, Viviana
%A Kirchhoff, Frank
%A Jacob, Timo
%A Kmiec, Dorota
%A Pichlmair, Andreas
%A Ensser, Armin
%A Sparrer, Konstantin Maria Johannes
%T Mutation T9I in Envelope confers autophagy resistance to SARS-CoV-2 Omicron.
%J iScience
%V 28
%N 7
%@ 2589-0042
%C St. Louis
%I Elsevier
%M DZNE-2025-00881
%P 112974
%D 2025
%X 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.
%K Biological sciences (Other)
%K Cell biology (Other)
%K Microbiology (Other)
%K Natural sciences (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40687831
%2 pmc:PMC12272759
%R 10.1016/j.isci.2025.112974
%U https://pub.dzne.de/record/280042