Multi-pronged human protein mimicry by SARS-CoV-2 reveals bifurcating potential for MHC detection and immune evasion

  1. AJ Venkatakrishnan
  2. Nikhil Kayal
  3. Praveen Anand
  4. Andrew D. Badley
  5. George M. Church
  6. Venky Soundararajan

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Abstract

The hand of molecular mimicry in shaping SARS-CoV-2 evolution and immune evasion remains to be deciphered. We identify 33 distinct 8-mer/9-mer peptides that are identical between SARS-CoV-2 and human proteomes, along similar extents of viral mimicry observed in other viruses. Interestingly, 20 novel peptides have not been observed in any previous human coronavirus (HCoV) strains. Four of the total mimicked 8-mers/9-mers map onto HLA-B*40:01, HLA-B*40:02, and HLA-B*35:01 binding peptides from human PAM, ANXA7, PGD, and ALOX5AP proteins. This mimicry of multiple human proteins by SARS-CoV-2 is made salient by the targeted genes being focally expressed in arteries, lungs, esophagus, pancreas, and macrophages. Further, HLA-A*03 restricted 8-mer peptides are shared broadly by human and coronaviridae helicases with primary expression of the mimicked human proteins in the neurons and immune cells. This study presents the first comprehensive scan of peptide mimicry by SARS-CoV-2 of the human proteome and motivates follow-up research into its immunological consequences.

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    SciScore for 10.1101/2020.06.19.161620: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

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    Table 2: Resources

    Software and Algorithms
    SentencesResources
    For comparison, we analyzed the protein sequences from 9434 viral species (taxons) from NCBI RefSeq (see Methods).
    RefSeq
    suggested: (RefSeq, RRID:SCR_003496)
    The UniProt database was used to download the 15 protein reference sequences for SARS-CoV.
    UniProt
    suggested: (UniProtKB, RRID:SCR_004426)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

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    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
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  2. Version published to 10.1101/2020.06.19.161620 on bioRxiv