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000280042 1001_ $$0P:(DE-2719)9003510$$aKlute, Susanne$$b0$$udzne
000280042 245__ $$aMutation T9I in Envelope confers autophagy resistance to SARS-CoV-2 Omicron.
000280042 260__ $$aSt. Louis$$bElsevier$$c2025
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000280042 520__ $$aOmicron has emerged as the most successful variant of SARS-CoV-2. In addition to mutations in Spike that mediate humoral immune escape, the Omicron-specific Envelope (E) T9I mutation has been associated with increased transmission fitness. However, the underlying mechanism remained unclear. Here, we demonstrate that the E T9I mutation confers resistance to autophagy. Rare Omicron patient isolates encoding the ancestral E T9 remain sensitive to autophagy. Conversely, introducing the E T9I mutation in recombinant 2020 SARS-CoV-2 renders it resistant to autophagy. Our data indicate that the E T9I mutation protects virions against lysosomal degradation. At the molecular level, the T9I mutation increases the localization of E at autophagic vesicles and promotes interaction with autophagy-associated proteins SNX12, STX12, TMEM87B, and ABCG2. Our results show that the E T9I mutation renders incoming virions resistant to autophagy, suggesting that evasion of this antiviral mechanism contributes to the efficient spread of Omicron.
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000280042 650_7 $$2Other$$aCell biology
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000280042 7001_ $$aNchioua, Rayhane$$b1
000280042 7001_ $$aCordsmeier, Arne$$b2
000280042 7001_ $$aVishwakarma, Jyoti$$b3
000280042 7001_ $$aKoepke, Lennart$$b4
000280042 7001_ $$aAlshammary, Hala$$b5
000280042 7001_ $$aJung, Christoph$$b6
000280042 7001_ $$0P:(DE-2719)9003503$$aHirschenberger, Maximilian$$b7$$udzne
000280042 7001_ $$0P:(DE-2719)9003500$$aHoenigsperger, Helene$$b8$$udzne
000280042 7001_ $$0P:(DE-2719)9003519$$aFischer, Jana-Romana$$b9$$udzne
000280042 7001_ $$0P:(DE-2719)9003505$$aSivarajan, Rinu$$b10$$udzne
000280042 7001_ $$aZech, Fabian$$b11
000280042 7001_ $$aStenger, Steffen$$b12
000280042 7001_ $$aSerra-Moreno, Ruth$$b13
000280042 7001_ $$aGonzalez-Reiche, Ana Silvia$$b14
000280042 7001_ $$aSordillo, Emilia Mia$$b15
000280042 7001_ $$avan Bakel, Harm$$b16
000280042 7001_ $$aSimon, Viviana$$b17
000280042 7001_ $$aKirchhoff, Frank$$b18
000280042 7001_ $$aJacob, Timo$$b19
000280042 7001_ $$aKmiec, Dorota$$b20
000280042 7001_ $$aPichlmair, Andreas$$b21
000280042 7001_ $$aEnsser, Armin$$b22
000280042 7001_ $$0P:(DE-2719)9003481$$aSparrer, Konstantin Maria Johannes$$b23$$eLast author$$udzne
000280042 773__ $$0PERI:(DE-600)2927064-9$$a10.1016/j.isci.2025.112974$$gVol. 28, no. 7, p. 112974 -$$n7$$p112974$$tiScience$$v28$$x2589-0042$$y2025
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