Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape

  1. Kevin R. McCarthy
  2. Linda J. Rennick
  3. Sham Nambulli
  4. Lindsey R. Robinson-McCarthy
  5. William G. Bain
  6. Ghady Haidar
  7. W. Paul Duprex

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Abstract

Influenza viruses evade immunity initiated by previous infection, which explains recurrent influenza pandemics. Unlike the error-prone RNA-dependent RNA polymerase of influenza, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and related viruses contain polymerases with proofreading activity. However, proofreading cannot correct deletions, which during a long-term persistent infection could result in the generation of viruses showing alteration of entire stretches of amino acids and the structures they form. McCarthy et al. identified an evolutionary signature defined by prevalent and recurrent deletions in the spike protein of SARS-CoV-2 at four antigenic sites. Deletion variants show human-to-human transmission of viruses with altered antigenicity.

Science , this issue p. 1139

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  1. Rapid Reviews Infectious Diseases

    Julie Overbaugh, Meghan Garrett

    Review 2: "Natural deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape"

    This study suggests that viral sequence variations within an immunocompromised patient with a 74 day diagnosis drive the virus escape from host immunity. Both reviewers considered this study to be reliable due to the methods.

  2. Rapid Reviews Infectious Diseases

    Mitnala Sasikala, Ravikanth Vishnubotla

    Review 1: "Natural deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape"

    This study suggests that viral sequence variations within an immunocompromised patient with a 74 day diagnosis drive the virus escape from host immunity. Both reviewers considered this study to be reliable due to the methods.

  3. Rapid Reviews Infectious Diseases

    Strength of evidence

    Reviewers: Mitnala Sasikala, Ravikanth Vishnubotla (Asian Institute of Gastroenterology) | 📗📗📗📗◻️
    Julie Overbaugh, Meghan Garrett (Fred Hutchinson Cancer Research Center) | 📗📗📗📗◻️

  4. Version published to 10.1126/science.abf6950
  5. ScreenIT

    SciScore for 10.1101/2020.11.19.389916: (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.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Primary antibodies [rabbit anti-SARS-CoV-2 S monoclonal antibody, 40150-R007, Sino Biological, 1/700 dilution and human 4A8 monoclonal antibody, 1 μg/ml, in PBS containing 0.1% (v/v) Triton X-100] were added and incubated at 37° Celsius for 1 hour.
    anti-SARS-CoV-2 S
    suggested: None
    Cells were washed three times with DPBS and secondary antibodies [goat anti-rabbit Alexa Fluor-568, Invitrogen, and goat anti-human Alexa Fluor-488, Invitrogen, diluted 1:400 in DPBS containing 0.1% (v/v) Triton X-100 were added and incubated at 37° Celsius for 1 hour.
    anti-rabbit
    suggested: None
    anti-human Alexa Fluor-488, Invitrogen,
    suggested: None
    An identical dilution series was prepared using H2214 monoclonal antibody as a negative control.
    H2214
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Cell lines: Human 293F cells were maintained at 37° Celsius with 5% CO2 in FreeStyle 293 Expression Medium (ThermoFisher) supplemented with penicillin and streptomycin.
    293F
    suggested: None
    Vero E6 cells were maintained at 37° Celsius with 5% CO2 in high glucose DMEM (Invitrogen) supplemented with 1% (v/v) Glutamax (Invitrogen) and 10% (v/v) fetal bovine serum (Invitrogen).
    Vero E6
    suggested: RRID:CVCL_XD71)
    Software and Algorithms
    SentencesResources
    FastTree (32) was used to generate a preliminary phylogeny, which we used to identify representatives of most clades and those sequences that interleaved between patients.
    FastTree
    suggested: (FastTree, RRID:SCR_015501)
    The final tree, using this subset of sequences was produced using RAxML (33).
    RAxML
    suggested: (RAxML, RRID:SCR_006086)
    For non-Senegalese samples, sequences obtained within 1-2 months of the variants of interest were aligned to MN985325 using MAFFT (30, 31).
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    Structure visualization: Structural figures were rendered in Pymol (The PyMOL Molecular Graphics System, Version 2.0 Schrödinger, LLC).
    PyMOL
    suggested: (PyMOL, RRID:SCR_000305)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.

  6. Version published to 10.1101/2020.11.19.389916v2 on bioRxiv
  7. ScreenIT

    SciScore for 10.1101/2020.11.19.389916: (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

    No key resources detected.

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.

    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.

  8. Version published to 10.1101/2020.11.19.389916v1 on bioRxiv