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

Analysis of the bat viruses most closely related to SARS‐CoV‐2 indicated that the virus probably required limited adaptation to spread in humans. Nonetheless, since its introduction in human populations, SARS‐CoV‐2 must have been subject to 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 nonepitope positions. Similar results were obtained for other human coronaviruses and for sarbecoviruses sampled in bats. Conversely, in the SARS‐CoV‐2 population, epitopes for CD4 + and CD8 + T cells were not more variable than nonepitope 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 evolves to elude the host humoral immune response, whereas recognition by T cells is not actively avoided by the virus. However, we also found a trend of lower diversity of T cell epitopes for common cold coronaviruses, indicating that epitope conservation per se is not directly linked to disease severity. We suggest that conservation serves to maintain epitopes that elicit tolerizing T cell responses or induce T cells with regulatory activity.

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  1. Version published to 10.1111/mec.15730
  2. 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.

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  3. Version published to 10.1101/2020.07.15.204610v1 on bioRxiv