How SARS-CoV-2 Omicron subvariants have evolved to evade host T-cell immunity SARSCoV2 COVID19 OmicronVariant Tcell MHC1 immunesystem virology research PNASNews Yale
By Neha MathurApr 15 2023Reviewed by Benedette Cuffari, M.Sc. In a recent article published in the journal PNAS, researchers investigate whether the severe acute respiratory syndrome coronavirus 2 and its variants of concern , especially Omicron, have evolved to evade CD8+ T cell-mediated immunity similar to how these VOCs have acquired mutations within the spike protein to resist neutralizing antibodies .
Several viruses have developed the ability to inhibit MHC-I processing. SARS-CoV-2, for example, uses its open reading frame 8 protein to autophagic-ally degrade MHC-I molecules and escape CTL surveillance. Up to 965 sequences of pre-Omicron and other SARS-CoV-2 lineages were downloaded from various sources, such as the Global Initiative on Sharing All Influenza Data database. ORF8 amino acid sequence alignment was performed to identify any nonsynonymous mutations in SARS-CoV-2 variants that resulted in differential MHC-I regulation.
Study findings The ancestral SARS-CoV-2 strain vigorously suppressed MHC-I surface expression, whereas pre-Omicron VOCs evolved only to some extent for modulating the MHC-I pathway. While all SARS-CoV-2 variants possess the potential to suppress MHC-I expression, the Omicron subvariants were associated with the highest ability to suppress surface MHC-I expression due to the T9I mutation in their E protein.
Conclusions SARS-CoV-2 uses multiple strategies to suppress MHC-I expression. Furthermore, MHC-I downregulation by SARS-CoV-2 was found to impair CTL recognition of infected cells for killing and the priming of CD8+ T-cells.
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