Speakers
Description
SARS-CoV-2 evolution is shaped by human adaptive immunity, with mutations that allow escape from the B-cell response conferring selective advantage and spreading in the population. Meanwhile, the role of the escape from T-cellular cytotoxic response remains controversial. Here, we study the origin and spread of SARS-CoV-2 variants that allow escape from presentation by the HLA class I alleles that are common in human populations. We find that both among the mutations that are characteristic of the variants of concern, and of those that have reached high frequencies in viral populations, a large proportion facilitates escape from T-cellular alleles. Mutations associated with escape from common HLA alleles reach higher frequencies than those that allow escape from less common HLA alleles. Moreover, viral escape mutations reach higher frequencies in those countries where the causal HLA alleles are more frequent, indicating that viral escape is driven by the local genetic composition of the human host population. Together, these data indicate that CTL escape is a major driver of SARS-CoV-2 evolution and an epidemiological concern, and reveal a novel facet of selection on this virus.
