Emerging mutation in SARS-CoV-2 facilitates escape from NK cell recognition and associates with enhanced viral fitness DOI Creative Commons
Eleni Bilev,

Nicole Wild,

Pouria Momayyezi

et al.

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(12), P. e1012755 - e1012755

Published: Dec. 9, 2024

In addition to adaptive immunity, natural killer (NK) cells of the innate immune system contribute control viral infections. The HLA-E-restricted SARS-CoV-2 Nsp13 232-240 epitope VMPLSAPTL renders infected susceptible NK by preventing binding inhibitory receptor NKG2A. Here, we report that a recently emerged methionine isoleucine substitution at position 2 (pM2I) impairs mutated HLA-E and diminishes HLA-E/peptide complex stability. Structural analyses revealed altered occupancy B-pocket as underlying cause for reduced presentation stability epitope. Functionally, correlated with elevated NKG2A well increased cell inhibition. Moreover, pM2I mutation associated enhanced estimated fitness was transmitted descendants BQ.1 variant. Interestingly, resembles sequences related peptides found in endemic common cold-causing human coronaviruses. Altogether, these findings indicate compromised peptide adaptation evade cell-mediated immunosurveillance enabling self-peptide restoring NKG2A-dependent inhibition cells.

Language: Английский

Emerging mutation in SARS-CoV-2 facilitates escape from NK cell recognition and associates with enhanced viral fitness DOI Creative Commons
Eleni Bilev,

Nicole Wild,

Pouria Momayyezi

et al.

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(12), P. e1012755 - e1012755

Published: Dec. 9, 2024

In addition to adaptive immunity, natural killer (NK) cells of the innate immune system contribute control viral infections. The HLA-E-restricted SARS-CoV-2 Nsp13 232-240 epitope VMPLSAPTL renders infected susceptible NK by preventing binding inhibitory receptor NKG2A. Here, we report that a recently emerged methionine isoleucine substitution at position 2 (pM2I) impairs mutated HLA-E and diminishes HLA-E/peptide complex stability. Structural analyses revealed altered occupancy B-pocket as underlying cause for reduced presentation stability epitope. Functionally, correlated with elevated NKG2A well increased cell inhibition. Moreover, pM2I mutation associated enhanced estimated fitness was transmitted descendants BQ.1 variant. Interestingly, resembles sequences related peptides found in endemic common cold-causing human coronaviruses. Altogether, these findings indicate compromised peptide adaptation evade cell-mediated immunosurveillance enabling self-peptide restoring NKG2A-dependent inhibition cells.

Language: Английский

Citations

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