Distinct Inductions of and Responses to Type I and Type III Interferons Promote Infections in Two SARS-CoV-2 Isolates

  1. Fu Hsin
  2. Tai-Ling Chao
  3. Yun-Rui Chan
  4. Han-Chieh Kao
  5. Wang-Da Liu
  6. Jann-Tay Wang
  7. Yu-Hao Pang
  8. Chih-Hui Lin
  9. Ya-Min Tsai
  10. Jing-Yi Lin
  11. Sui-Yuan Chang
  12. Helene Minyi Liu

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Abstract

The recent emerging coronavirus, SARS-CoV-2, has been rapidly and widely spread and causing an ongoing viral pneumonia outbreak worldwide. It has been observed that SARS-CoV-2 patients show a rather long and asymptomatic incubation time. We characterized the abilities to induce and to response to IFNβ/IFNλ1 of two or our clinical isolates, SARS-CoV-2/NTU01/TWN/human/2020 and SARS-CoV-2/NTU02/TWN/human/2020, which exhibit only two amino acid differences over the ∼30kb viral genome. We found that both isolates may infect Huh7, A549 and Calu-3 cells, yet the RIG-I-like receptor-dependent antiviral signaling was poorly induced in these cells in the early infections. Unexpectedly, we found that the intracellular vRNA levels of these isolates were sustained upon to type I/III IFN treatments, and this phenotype was more pronounced in the Taiwan/NTU01/2020 isolate. The type I/III IFN responses are antiviral but partially proviral in the case of SARS-CoV-2 infections. Poor induction and response to innate immunity may contribute to destitute neutralization index of the antibody produced, and indeed we found that the patient serum could not efficiently neutralize SARS-CoV-2 virions. With better understandings of the interplay between SARS-CoV-2 and the host antiviral innate immunity, our report may provide new insights for the regimen of therapies for SARS-CoV-2 infected patients.

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  1. ScreenIT

    SciScore for 10.1101/2020.04.30.071357: (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

    Experimental Models: Cell Lines
    SentencesResources
    Cells and Viruses: Huh7, A549, Calu-3, VeroE6 and LLC-MK2 cells were propagated in Dulbecco’s modified Eagle’s medium DMEM; Gibco-BRL, USA) supplemented with 10% fetal bovine serum (FBS; GIBCO-BRL, USA), penicillin G sodium 100 units/mL, streptomycin sulfate 100 μg/mL and amphotericin B 250 ng/mL (antibiotic-antimycotic; Gibco-BRL,
    Huh7
    suggested: None
    A549
    suggested: None
    Calu-3
    suggested: None
    LLC-MK2
    suggested: None
    Briefly, the VeroE6 cells were seeded at 2 × 105 cells/well in the 24-well tissue culture plates with DMEM containing 10% FCS and antibiotics one day before infection.
    VeroE6
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)

    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 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.

  2. Version published to 10.1101/2020.04.30.071357v1 on bioRxiv