Role of glycosylation mutations at the N-terminal domain of SARS-CoV-2 XEC variant in immune evasion, cell-cell fusion, and spike stability DOI Creative Commons

Pei Li,

Julia N. Faraone, Cheng Chih Hsu

и другие.

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, producing new variants that drive global disease 2019 surges. XEC, a recombinant of KS.1.1 and KP.3.3, contains T22N F59S mutations in the spike protein’s N-terminal domain (NTD). The mutation, similar DelS31 mutation KP.3.1.1, introduces potential N-linked glycosylation site XEC. In this study, we examined neutralizing antibody (nAb) response effects sera from bivalent-vaccinated healthcare workers, BA.2.86/JN.1 wave-infected patients, XBB.1.5 monovalent-vaccinated hamsters, assessing responses XEC alongside D614G, JN.1, KP.3, KP.3.1.1. demonstrated significantly reduced neutralization titers across all cohorts, largely due mutation. Notably, removal sites KP.3.1.1 substantially restored nAb titers. Antigenic cartography analysis revealed be more antigenically distinct its common ancestral compared with as determining factor. Similar showed cell-cell fusion relative parental change attributed glycosylation. We also observed S1 shedding for which was reversed by ablation mutations, respectively. Molecular modeling suggests alter hydrophobic interactions adjacent protein residues, impacting both conformational stability neutralization. Overall, our findings underscore pivotal role NTD shaping SARS-CoV-2 biology immune escape mechanisms. IMPORTANCE continuous evolution severe has led emergence novel enhanced evasion properties, posing challenges current vaccination strategies. This study identifies key (NTD) particularly recent variant, impacts antigenicity, neutralization, stability. introduction an through T22N, along antigenic shift driven F59S, highlights how subtle can drastically viral recognition. By demonstrating restores sensitivity, work provides crucial insights into molecular mechanisms governing escape. Additionally, on contribute broader understanding variant fitness transmissibility. These emphasize importance monitoring emerging lineages support need adaptive vaccine designs counteract ongoing evolution.

Язык: Английский

Role of glycosylation mutations at the N-terminal domain of SARS-CoV-2 XEC variant in immune evasion, cell-cell fusion, and spike stability DOI Creative Commons

Pei Li,

Julia N. Faraone, Cheng Chih Hsu

и другие.

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, producing new variants that drive global disease 2019 surges. XEC, a recombinant of KS.1.1 and KP.3.3, contains T22N F59S mutations in the spike protein’s N-terminal domain (NTD). The mutation, similar DelS31 mutation KP.3.1.1, introduces potential N-linked glycosylation site XEC. In this study, we examined neutralizing antibody (nAb) response effects sera from bivalent-vaccinated healthcare workers, BA.2.86/JN.1 wave-infected patients, XBB.1.5 monovalent-vaccinated hamsters, assessing responses XEC alongside D614G, JN.1, KP.3, KP.3.1.1. demonstrated significantly reduced neutralization titers across all cohorts, largely due mutation. Notably, removal sites KP.3.1.1 substantially restored nAb titers. Antigenic cartography analysis revealed be more antigenically distinct its common ancestral compared with as determining factor. Similar showed cell-cell fusion relative parental change attributed glycosylation. We also observed S1 shedding for which was reversed by ablation mutations, respectively. Molecular modeling suggests alter hydrophobic interactions adjacent protein residues, impacting both conformational stability neutralization. Overall, our findings underscore pivotal role NTD shaping SARS-CoV-2 biology immune escape mechanisms. IMPORTANCE continuous evolution severe has led emergence novel enhanced evasion properties, posing challenges current vaccination strategies. This study identifies key (NTD) particularly recent variant, impacts antigenicity, neutralization, stability. introduction an through T22N, along antigenic shift driven F59S, highlights how subtle can drastically viral recognition. By demonstrating restores sensitivity, work provides crucial insights into molecular mechanisms governing escape. Additionally, on contribute broader understanding variant fitness transmissibility. These emphasize importance monitoring emerging lineages support need adaptive vaccine designs counteract ongoing evolution.

Язык: Английский

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