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| 001 | 280042 | ||
| 005 | 20250824001722.0 | ||
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| 100 | 1 | _ | |a Klute, Susanne |0 P:(DE-2719)9003510 |b 0 |u dzne |
| 245 | _ | _ | |a Mutation T9I in Envelope confers autophagy resistance to SARS-CoV-2 Omicron. |
| 260 | _ | _ | |a St. Louis |c 2025 |b Elsevier |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 520 | _ | _ | |a 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. |
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| 700 | 1 | _ | |a Nchioua, Rayhane |b 1 |
| 700 | 1 | _ | |a Cordsmeier, Arne |b 2 |
| 700 | 1 | _ | |a Vishwakarma, Jyoti |b 3 |
| 700 | 1 | _ | |a Koepke, Lennart |b 4 |
| 700 | 1 | _ | |a Alshammary, Hala |b 5 |
| 700 | 1 | _ | |a Jung, Christoph |b 6 |
| 700 | 1 | _ | |a Hirschenberger, Maximilian |0 P:(DE-2719)9003503 |b 7 |u dzne |
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| 700 | 1 | _ | |a Zech, Fabian |b 11 |
| 700 | 1 | _ | |a Stenger, Steffen |b 12 |
| 700 | 1 | _ | |a Serra-Moreno, Ruth |b 13 |
| 700 | 1 | _ | |a Gonzalez-Reiche, Ana Silvia |b 14 |
| 700 | 1 | _ | |a Sordillo, Emilia Mia |b 15 |
| 700 | 1 | _ | |a van Bakel, Harm |b 16 |
| 700 | 1 | _ | |a Simon, Viviana |b 17 |
| 700 | 1 | _ | |a Kirchhoff, Frank |b 18 |
| 700 | 1 | _ | |a Jacob, Timo |b 19 |
| 700 | 1 | _ | |a Kmiec, Dorota |b 20 |
| 700 | 1 | _ | |a Pichlmair, Andreas |b 21 |
| 700 | 1 | _ | |a Ensser, Armin |b 22 |
| 700 | 1 | _ | |a Sparrer, Konstantin Maria Johannes |0 P:(DE-2719)9003481 |b 23 |e Last author |u dzne |
| 773 | _ | _ | |a 10.1016/j.isci.2025.112974 |g Vol. 28, no. 7, p. 112974 - |0 PERI:(DE-600)2927064-9 |n 7 |p 112974 |t iScience |v 28 |y 2025 |x 2589-0042 |
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