Antigenic variation of SARS-CoV-2 in response to immune pressure

  1. Diego Forni
  2. Rachele Cagliani
  3. Chiara Pontremoli
  4. Alessandra Mozzi
  5. Uberto Pozzoli
  6. Mario Clerici
  7. Manuela Sironi

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Abstract

The ongoing evolution of SARS-CoV-2 is expected to be at least partially driven by the selective pressure imposed by the human immune system. We exploited the availability of a large number of high-quality SARS-CoV-2 genomes, as well as of validated epitope predictions, to show that B cell epitopes in the spike glycoprotein (S) and in the nucleocapsid protein (N) have higher diversity than non-epitope positions. Similar results were obtained for other human coronaviruses. Conversely, in the SARS-CoV-2 population, epitopes for CD4 + and CD8 + T cells were not more variable than non-epitope positions. A significant reduction in epitope variability was instead observed for some of the most immunogenic proteins (S, N, ORF8, and ORF3a). Analysis over longer evolutionary time-frames indicated that this effect is not due to differential constraints. These data indicate that SARS-CoV-2 is evolving to elude the host humoral immune response, whereas recognition by T cells might benefit the virus.

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  1. ScreenIT

    SciScore for 10.1101/2020.07.15.204610: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    For all the other human coronaviruses, as well as for a set of non-human infecting sarbecoviruses, sequences of either complete genome or single ORFs (i.e. nucleocapsid and spike protein) were retrieved from the National Center for Biotechnology Information database (NCBI, http://www.ncbi.nlm.nih.gov/).
    http://www.ncbi.nlm.nih.gov/
    suggested: (GENSAT at NCBI - Gene Expression Nervous System Atlas, RRID:SCR_003923)
    Alignments were generated using MAFFT (Katoh and Standley, 2013).
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)

    Results from OddPub: Thank you for sharing your code.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    This clearly represents a limitation of this study, but the modest amount of genetic diversity in the SARS-CoV-2 population does not presently allow analysis of single epitope regions. Moreover, more detailed and robust analyses will indubitably require the systematic, experimental definition of T and B cell epitopes in the SARS-CoV-2 proteome.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1101/2020.07.15.204610 on bioRxiv