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SARS-CoV-2 ORF1abA1061S potentiate autoreactive T cell responses via epitope mimicry: an explanation to hepatitis of unknown cause

View ORCID ProfileYu Wang, Yuexing Liu
doi: https://doi.org/10.1101/2022.05.16.491922
Yu Wang
1Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences; Shanghai 200031, China
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  • For correspondence: oucwangyu@163.com yancylau@163.com
Yuexing Liu
2Guangzhou Laboratory, Guangzhou 510005, China
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  • For correspondence: oucwangyu@163.com yancylau@163.com
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Abstract

The World Health Organization have recently announced outbreak news of acute, severe hepatitis of unknown cause in children under a Covid-19 pandemic. Whether it is associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still under debating. Here, we performed genomic sequence alignment analysis of the genome of SARS-Cov-2 (Wuhan-hu-1) to the human genome reference. Sequence analysis revealed that the SARS-CoV-2 ORF1ab1056-1173 presented high identities with the human protein PAPR1453-176(3Q6Z_A). After searching the fully sequenced SARS-CoV-2 genomes deposited in GISAID (https://www.gisaid.org/), we detected 170 SARS-CoV-2 variants with mutation in ORF1ab1061, where alanine (A) was substituted by serine (S). This alteration made a 7-amino acid peptide (VVVNASN) in ORF1ab1056-1062 identical to its counterpart in PARP1453-59(3Q6Z_A). HLA prediction suggested that the peptides with high identities in PARP14 and ORF1ab could be presented by a same globally prevalent HLA-A*11:01 molecule. And in consistent with the first reported case of hepatitis of unknown, SARS-CoV-2 ORF1abVVVNASN variants were mostly identified as Delta lineages in UK by the late 2021, with an overall frequency of 0.00161%. Thus, our preliminary results raised a possibility that infection by SARS-CoV-2 ORF1abVVVNASN variant might elicit an autoimmune T cell response via epitope mimicry and is associated with the outbreak of unknown hepatitis. We anticipated that these findings will alert the human societies to pay more attention to rare mutations beyond the spike proteins.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Figure 1 revised. References added.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 20, 2022.
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SARS-CoV-2 ORF1abA1061S potentiate autoreactive T cell responses via epitope mimicry: an explanation to hepatitis of unknown cause
Yu Wang, Yuexing Liu
bioRxiv 2022.05.16.491922; doi: https://doi.org/10.1101/2022.05.16.491922
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SARS-CoV-2 ORF1abA1061S potentiate autoreactive T cell responses via epitope mimicry: an explanation to hepatitis of unknown cause
Yu Wang, Yuexing Liu
bioRxiv 2022.05.16.491922; doi: https://doi.org/10.1101/2022.05.16.491922

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