| Title: | C > U mutations generate immunogenic peptides in SARS-CoV-2 |
| Journal: | Nature Communications |
| Published: | 19 Nov 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41258064/ |
| DOI: | https://doi.org/10.1038/s41467-025-65251-8 |
Publication 18887
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Abstract
The rapid spread of SARS-CoV-2 worldwide has given rise to numerous variants. While the impact of viral mutations on antibody escape has been extensively studied, an unresolved issue concerns how emerging mutations shape HLA-restricted T-cell immune responses. Here, we analyse SARS-CoV-2 genomic variants, showing that 27% of the mutations are C > U transitions, a phenomenon common in human RNA viruses and primarily attributed to APOBEC3 enzyme-driven mutagenesis. We find that this mutation bias generally enhances viral peptide binding to human leukocyte antigen class I (HLA-I) molecules, producing immunogenic epitopes that trigger cytotoxic adaptive immune responses in most individuals across diverse populations. We also identify several HLA-I variants that are especially well-suited for presenting viral epitopes generated by these mutations. Intriguingly, individuals carrying these specific alleles are predominantly located in South and East Asia. Finally, we show that carrying HLA-I molecules that are less likely to bind C > U-induced viral peptides increases risk for severe COVID-19 disease. Our work suggests a link between C > U hypermutation and HLA-I-based presentation of viral epitopes, which may reflect the evolutionary outcome of ancient RNA virus pandemics. More broadly, our findings imply that SARS-CoV-2 diversification leads to ongoing gains of T-cell epitopes despite natural selection favouring immune escape.</p>
7 Keywords
- COVID-19
- Epitopes, T-Lymphocyte
- Histocompatibility Antigens Class I
- Humans
- Mutation
- Peptides
- SARS-CoV-2
11 Authors
- Gergő Mihály Balogh
- Balázs Koncz
- Leó Asztalos
- Eszter Ari
- Nikolett Gémes
- Gábor J. Szebeni
- Benjamin Tamás Papp
- Franciska Tóth
- Balázs Papp
- Csaba Pál
- Máté Manczinger
1 Application
| Application ID | Title |
|---|---|
| 44917 | The role of epitope-binding features of HLA alleles in health and disease. |
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