An emerging SARS-CoV-2 mutant evading cellular immunity and increasing viral infectivity

  1. Chihiro Motozono
  2. Mako Toyoda
  3. Jiri Zahradnik
  4. Terumasa Ikeda
  5. Akatsuki Saito
  6. Toong Seng Tan
  7. Isaac Ngare
  8. Hesham Nasser
  9. Izumi Kimura
  10. Keiya Uriu
  11. Yusuke Kosugi
  12. Shiho Torii
  13. Akiko Yonekawa
  14. Nobuyuki Shimono
  15. Yoji Nagasaki
  16. Rumi Minami
  17. Takashi Toya
  18. Noritaka Sekiya
  19. Takasuke Fukuhara
  20. Yoshiharu Matsuura
  21. Gideon Schreiber
  22. The Genotype to Phenotype Japan (G2P-Japan) consortium
  23. So Nakagawa
  24. Takamasa Ueno
  25. Kei Sato

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Abstract

During the current SARS-CoV-2 pandemic that is devastating the modern societies worldwide, many variants that naturally acquire multiple mutations have emerged. Emerging mutations can affect viral properties such as infectivity and immune resistance. Although the sensitivity of naturally occurring SARS-CoV-2 variants to humoral immunity has recently been investigated, that to human leukocyte antigen (HLA)-restricted cellular immunity remains unaddressed. Here we demonstrate that two recently emerging mutants in the receptor binding domain of the SARS-CoV-2 spike protein, L452R (in B.1.427/429) and Y453F (in B.1.298), can escape from the HLA-24-restricted cellular immunity. These mutations reinforce the affinity to viral receptor ACE2, and notably, the L452R mutation increases protein stability, viral infectivity, and potentially promotes viral replication. Our data suggest that the HLA-restricted cellular immunity potentially affects the evolution of viral phenotypes, and the escape from cellular immunity can be a further threat of the SARS-CoV-2 pandemic.

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  3. ScreenIT

    SciScore for 10.1101/2021.04.02.438288: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    KEY RESOURCES TABLE: RESOURCE AVAILABILITY: EXPERIMENTAL MODEL AND SUBJECT DETAILS: METHOD DETAILS: QUANTIFICATION AND STATISTICAL ANALYSIS: Data analyses were performed using Prism 7 (GraphPad Software).
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    A limitation of this study is that the effects of the L452 and Y453 substitutions on viral pathogenicity, mortality and transmissibility remain unaddressed. To fully characterize the virological features of these mutants, further investigations using animal models and epidemiological data will be required. Nevertheless, here we showed direct evidence suggesting that the mutations in the RBM including L452R (in the B.1.427/429 lineage) and Y453F (in the B1.1.298 lineage) potentially escape from the HLA-A24-resticted cellular immunity, and further, the L452R mutant increase its replication capacity. Therefore, these variants, particularly those possessing the L452R mutations, such as the B.1.427/429 lineage, can be the potential threat for these countries and regions with predominant HLA-A24 individuals, and deep surveillance and tracing the epidemic of these variants will be urgently required.

    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

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2021.04.02.438288 on bioRxiv