Mutation T9I in Envelope confers autophagy resistance to SARS-CoV-2 Omicron

Le résumé fourni par la source

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.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.