Comparative Transcriptome Analysis Reveals the Intensive Early Stage Responses of Host Cells to SARS-CoV-2 Infection

  1. Jiya Sun
  2. Fei Ye
  3. Aiping Wu
  4. Ren Yang
  5. Mei Pan
  6. Jie Sheng
  7. Wenjie Zhu
  8. Longfei Mao
  9. Ming Wang
  10. Zanxian Xia
  11. Baoying Huang
  12. Wenjie Tan
  13. Taijiao Jiang

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a widespread outbreak of highly pathogenic coronavirus disease 2019 (COVID-19). It is therefore important and timely to characterize interactions between the virus and host cell at the molecular level to understand its disease pathogenesis. To gain insights, we performed high-throughput sequencing that generated time-series data simultaneously for bioinformatics analysis of virus genomes and host transcriptomes implicated in SARS-CoV-2 infection. Our analysis results showed that the rapid growth of the virus was accompanied by an early intensive response of host genes. We also systematically compared the molecular footprints of the host cells in response to SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV). Upon infection, SARS-CoV-2 induced hundreds of up-regulated host genes hallmarked by a significant cytokine production, followed by virus-specific host antiviral responses. While the cytokine and antiviral responses triggered by SARS-CoV and MERS-CoV were only observed during the late stage of infection, the host antiviral responses during the SARS-CoV-2 infection were gradually enhanced lagging behind the production of cytokine. The early rapid host responses were potentially attributed to the high efficiency of SARS-CoV-2 entry into host cells, underscored by evidence of a remarkably up-regulated gene expression of TPRMSS2 soon after infection. Taken together, our findings provide novel molecular insights into the mechanisms underlying the infectivity and pathogenicity of SARS-CoV-2.

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  1. Version published to 10.3389/fmicb.2020.593857
  2. ScreenIT

    SciScore for 10.1101/2020.04.30.071274: (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
    Vero cells (ATCC, CCL-81) were cultured at 37 °C in Dulbecco’s modified Eagle’s medium (DMEM, Gibco) supplemented with 10% FBS (Gibco) in the atmosphere with 5% CO2.
    Vero
    suggested: None
    Triplicate samples of mock-infected and virus-infected Calu-3 cells were harvested at different times between 0 and 24 hour post-infection (hpi).
    Calu-3
    suggested: KCLB Cat# 30055, RRID:CVCL_0609)
    Software and Algorithms
    SentencesResources
    Data analysis: Raw reads were filtered to obtain clean data by Trimmomatic (v0.35) (With parameters ‘ILLUMINACLIP:adapter.fa:2:30:10 HEADCROP:10 LEADING:3 TRAILING:3 SLIDINGWINDOW:4:15 MINLEN:36’)[12].
    Trimmomatic
    suggested: (Trimmomatic, RRID:SCR_011848)
    The cleaned data were mapped to the human GRCh38 reference genome using STAR aligner (v2.7.2a)[13].
    STAR
    suggested: (STAR, RRID:SCR_015899)
    The R package DESeq2 was applied to further identify Differentially Expressed Genes (DEGs) (FDR<0.05, |log2FC|>=1) [15].
    DESeq2
    suggested: (DESeq, RRID:SCR_000154)
    For analysis of microarray data of SARS-CoV and MERS-CoV, normalization and identification of DEGs (FDR<0.05, |log2FC|>=1) were conducted using the R package limma [17].
    limma
    suggested: (LIMMA, RRID:SCR_010943)

    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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  3. Version published to 10.1101/2020.04.30.071274v1 on bioRxiv