tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2026 Sep;123(35):e2619192123.
doi: 10.1073/pnas.2619192123. Epub 2026 Aug 24.
Ekaterina D Riumina # 1 , Evgeniia I Alekseeva # 1 , Galya V Klink # 2 , Stepan Feigin 3 , Iaroslava Vinogradova 4 , Natalia Ivanova 5 , Dmitry Dianov 5 , Ksenia Zornikova 5 , Vassa Davydova 5 , Apollinariya Bogolyubova 5 , Georgii A Bazykin 6
Affiliations
The role of escape from the cytotoxic T cell (CTL) response in Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) evolution remains controversial. Here, we study the origin and spread of SARS-CoV-2 variants whose mutations reduce presentation by the human leukocyte antigen (HLA) class I alleles common in human populations. We find that 35% of mutations that are characteristic of the variants of concern, and 39% of all subsequent viral mutations, facilitate escape of viral epitopes from presentation. Mutations allowing escape from more common HLA alleles reach higher frequencies, particularly in those countries where these HLA alleles are more frequent, indicating that escape is selected by the local genetic composition of the human host population. We also show that viral mutations that accumulated in general-population transmission chains matched population HLA class I allele frequencies as well as, or better than, mutations acquired during persistent infections, suggesting that selection in favor of escape mutations is not limited to immunocompromised individuals. Together, these data reveal CTL escape as a facet of selection, a driver of evolution, and an epidemiological concern for SARS-CoV-2.
Keywords: HLA; SARS-CoV-2; T cell escape; epidemiology; viral evolution.
. 2026 Sep;123(35):e2619192123.
doi: 10.1073/pnas.2619192123. Epub 2026 Aug 24.
HLA class I escape drives the evolution of SARS-CoV-2 in human populations
Ekaterina D Riumina # 1 , Evgeniia I Alekseeva # 1 , Galya V Klink # 2 , Stepan Feigin 3 , Iaroslava Vinogradova 4 , Natalia Ivanova 5 , Dmitry Dianov 5 , Ksenia Zornikova 5 , Vassa Davydova 5 , Apollinariya Bogolyubova 5 , Georgii A Bazykin 6
Affiliations
- PMID: 42636373
- DOI: 10.1073/pnas.2619192123
Abstract
The role of escape from the cytotoxic T cell (CTL) response in Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) evolution remains controversial. Here, we study the origin and spread of SARS-CoV-2 variants whose mutations reduce presentation by the human leukocyte antigen (HLA) class I alleles common in human populations. We find that 35% of mutations that are characteristic of the variants of concern, and 39% of all subsequent viral mutations, facilitate escape of viral epitopes from presentation. Mutations allowing escape from more common HLA alleles reach higher frequencies, particularly in those countries where these HLA alleles are more frequent, indicating that escape is selected by the local genetic composition of the human host population. We also show that viral mutations that accumulated in general-population transmission chains matched population HLA class I allele frequencies as well as, or better than, mutations acquired during persistent infections, suggesting that selection in favor of escape mutations is not limited to immunocompromised individuals. Together, these data reveal CTL escape as a facet of selection, a driver of evolution, and an epidemiological concern for SARS-CoV-2.
Keywords: HLA; SARS-CoV-2; T cell escape; epidemiology; viral evolution.