HLA class I escape drives the evolution of SARS-CoV-2 in human populations

PNAS, США. 2026. Vol. 123. No. 35. P. 1–20.

Ekaterina D. Riumina, Klink G. V., Alekseeva E., Feigin S., Vinogradova I., Ivanova N., Dianov D., Zornikova K., Davydova V., Bogolyubova A., Bazykin G.

The role of escape from the cytotoxic T cell (CTL) response in SARS-CoV-2 evolution remains controversial. Here, we study the origin and spread of SARS-CoV-2 variants whose mutations reduce presentation by the 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: коронавирус COVID-19, Вирусная эволюция, Adaptive immunity, adaptive evolution, адаптивный иммунитет, SARS-CoV2, virus evolution, адаптивная эволюция

Publication based on the results of: Development of new mathematical and neural network based models and inference methods for population and evolutionary genomics and their applications for diagnostics and therapy of infectious and oncological disease (2025)