SARS-CoV-2 and Malayan pangolin coronavirus infect human endoderm, ectoderm and induced lung progenitor cells

  1. Bixia Hong
  2. Xinyuan Lai
  3. Yangzhen Chen
  4. Tianming Luo
  5. Xiaoping An
  6. Lihua Song
  7. Hui Zhuang
  8. Huahao Fan
  9. Tong Li
  10. Kuanhui Xiang
  11. Yigang Tong

Reviewed by

Read the full article

Listed in

Log in to save this article

Abstract

Since the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in several somatic cells, little is known about the infection of SASRS-CoV-2 and its related pangolin coronavirus (GX_P2V). Here we present for the first time that SARS-CoV-2 pseudovirus and GX_P2V could infect lung progenitor and even anterior foregut endoderm cells causing these cells death, which differentiated from human embryonic stem cells (hESCs). The infection and replication of SARS-CoV-2 and GX_P2V were inhibited when treated with whey protein of breastmilk and Remdesivir, confirming that these two viruses could infect lung progenitor and even anterior foregut endoderm. Moreover, we found that SARS-CoV-2 pseudovirus could infect endoderm and ectoderm. We found that whey protein blocked SARS-CoV-2 infecting these cells. In line with the SARS-CoV-2 results, GX_P2V could also infected endoderm and ectoderm, and also was inhibited by Remdesivir treatment. Although expressing coronavirus related receptor such as ACE2 and TMPRSS2, mesoderm cells are not permissive for SARS-CoV-2 and GX_P2V infection, which needed further to study the mechanisms. Interestingly, we also found that hESCs, which also express ACE2 and TMPRSS2 markers, are permissive for GX_P2V but not SARS-CoV-2 pseudovirus infection and replication, indicating the widespread cell types for GX_P2V infection. Heparin treatment blocked efficiently viral infection. These results provided insight that these stem cells maybe provided a stable repository of coronavirus function or genome. The potential consequence of SARS-CoV-2 and animal coronavirus such as GX_P2V infection in hESCs, germ layer and induced progenitors should be closely monitored.

Article activity feed

  1. Version published to 10.1101/2020.09.25.313270v2 on bioRxiv
  2. ScreenIT

    SciScore for 10.1101/2020.09.25.313270: (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
    Antibodies against nucleocapsid protein of anti-SARS-CoV-2 N protein (Genscript) and GAPDH of anti-GAPDH (Proteintech) were used at 1:3000 dilutions.
    Antibodies against nucleocapsid protein of anti-SARS-CoV-2 N protein ( Genscript )
    suggested: None
    GAPDH
    suggested: (LSBio (LifeSpan Cat# LS-C41945-3000, RRID:AB_1054935)
    The second antibody of HRP-conjugated affinipure Goat anti-mouse IgG (H+L) was diluted at 1:20000.
    anti-mouse IgG
    suggested: None
    The primary antibodies are anti-OCT4 rabbit polyclonal antibody (Proteintech), anti-SSEA-4 antibody (STEMCELL Technologies), anti-Sox17 antibody (R&D System), anti-Brachyury antibody (Cell Signaling Technology) and ani-Nestin antibody (R&D System).
    anti-OCT4
    suggested: None
    anti-SSEA-4
    suggested: None
    anti-Sox17
    suggested: None
    anti-Brachyury antibody ( Cell Signaling Technology )
    suggested: None
    ani-Nestin
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Other cell lines, coronavirus and key reagents: Vero E6 cells were cultured in high-glucose-containing Dulbecco’s Modified Eagle Medium supplemented with 10% fetal bovine serum.
    Vero E6
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analysis: Statistical analyses were analyzed using GraphPad Prism 8 software (GraphPad Software Inc.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    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: 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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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.
    • No funding statement was detected.
    • 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.

  3. Version published to 10.1101/2020.09.25.313270v1 on bioRxiv