Human herpesvirus diversity is altered in HLA class I binding peptides

[Significance] Viruses evolve to evade immune recognition that may otherwise limit transmission. Presentation of virus peptides by human leukocyte antigen (HLA) class I is a necessary step in the recognition of infection by immune cells. Virus adaptation to evade this immune recognition has not been formally tested across the diversity of HLA class I allotypes and virus strains. We analyzed genetic diversity of three human herpesviruses across peptides that bind diverse HLA class I allotypes. We find that adaptation to evade HLA class I recognition may be a general phenomenon shaping human herpesvirus genetic diversity, particularly for those proteins expressed during viral latency. This broad scope, across human and virus diversity, provides a unique comparative perspective of human–herpesvirus coevolution.