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| Home > Publications Database > Mutation T9I in Envelope confers autophagy resistance to SARS-CoV-2 Omicron. |
| Home > Publications Database > Mutation T9I in Envelope confers autophagy resistance to SARS-CoV-2 Omicron. |
| Journal Article | DZNE-2025-00881 |
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2025
Elsevier
St. Louis
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Please use a persistent id in citations: doi:10.1016/j.isci.2025.112974
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.
Keyword(s): Biological sciences ; Cell biology ; Microbiology ; Natural sciences
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