Abstract

SummaryModifications in HLA‐I expression are found in many viral diseases. They represent one of the immune evasion strategies most widely used by viruses to block antigen presentation and NK cell response, and SARS‐CoV‐2 is no exception. These alterations result from a combination of virus‐specific factors, genetically encoded mechanisms, and the status of host defences and range from loss or upregulation of HLA‐I molecules to selective increases of HLA‐I alleles. In this review, I will first analyse characteristic features of altered HLA‐I expression found in SARS‐CoV‐2. I will then discuss the potential factors underlying these defects, focussing on HLA‐E and class‐I‐related (like) molecules and their receptors, the most documented HLA‐I alterations. I will also draw attention to potential differences between cells transfected to express viral proteins and those presented as part of authentic infection. Consideration of these factors and others affecting HLA‐I expression may provide us with improved possibilities for research into cellular immunity against viral variants.

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