CD209L/L-SIGN and CD209/DC-SIGN act as receptors for SARS-CoV-2

  1. Razie Amraei
  2. Wenqing Yin
  3. Marc A. Napoleon
  4. Ellen L. Suder
  5. Jacob Berrigan
  6. Qing Zhao
  7. Judith Olejnik
  8. Kevin Brown Chandler
  9. Chaoshuang Xia
  10. Jared Feldman
  11. Blake M. Hauser
  12. Timothy M. Caradonna
  13. Aaron G. Schmidt
  14. Suryaram Gummuluru
  15. Elke Muhlberger
  16. Vipul Chitalia
  17. Catherine E. Costello
  18. Nader Rahimi

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Abstract

As the COVID-19 pandemic continues to spread, investigating the processes underlying the interactions between SARS-CoV-2 and its hosts is of high importance. Here, we report the identification of CD209L/L-SIGN and the related protein CD209/DC-SIGN as receptors capable of mediating SARS-CoV-2 entry into human cells. Immunofluorescence staining of human tissues revealed prominent expression of CD209L in the lung and kidney epithelium and endothelium. Multiple biochemical assays using a purified recombinant SARS-CoV-2 spike receptor binding domain (S-RBD) or S1 encompassing both NTB and RBD and ectopically expressed CD209L and CD209 revealed that CD209L and CD209 interact with S-RBD. CD209L contains two N- glycosylation sequons, at sites N92 and N361, but we determined that only site N92 is occupied. Removal of the N -glycosylation at this site enhances the binding of S-RBD with CD209L. CD209L also interacts with ACE2, suggesting a role for heterodimerization of CD209L and ACE2 in SARS-CoV-2 entry and infection in cell types where both are present. Furthermore, we demonstrate that human endothelial cells are permissive to SARS-CoV-2 infection and interference with CD209L activity by knockdown strategy or with soluble CD209L inhibits virus entry. Our observations demonstrate that CD209L and CD209 serve as alternative receptors for SARS-CoV-2 in disease-relevant cell types, including the vascular system. This property is particularly important in tissues where ACE2 has low expression or is absent, and may have implications for antiviral drug development.

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  1. Version published to 10.1101/2020.06.22.165803v3 on bioRxiv
  2. Version published to 10.1101/2020.06.22.165803v2 on bioRxiv
  3. ScreenIT

    SciScore for 10.1101/2020.06.22.165803: (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
    The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE 53 partner repository with the dataset identifier PXD021309.
    PRIDE
    suggested: (Pride-asap, RRID:SCR_012052)

    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

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  4. Version published to 10.1101/2020.06.22.165803v1 on bioRxiv