Transcriptomic profiling and genomic mutational analysis of Human coronavirus (HCoV)-229E -infected human cells

  1. Nehemya Friedman
  2. Jasmine Jacob-Hirsch
  3. Yaron Drori
  4. Eyal Eran
  5. Nitzan Kol
  6. Omri Nayshool
  7. Ella Mendelson
  8. Gideon Rechavi
  9. Michal Mandelboim

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Abstract

Human coronaviruses (HCoVs) cause mild to severe respiratory infection. Most of the common cold illnesses are caused by one of four HCoVs, namely HCoV-229E, HCoV-NL63, HCoV-HKU1 and HCoV-OC43. Several studies have applied global transcriptomic methods to understand host responses to HCoV infection, with most studies focusing on the pandemic severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV) and the newly emerging SARS-CoV-2. In this study, Next Generation Sequencing was used to gain new insights into cellular transcriptomic changes elicited by alphacoronavirus HCoV-229E. HCoV-229E-infected MRC-5 cells showed marked downregulation of superpathway of cholesterol biosynthesis and eIF2 signaling pathways. Moreover, upregulation of cyclins, cell cycle control of chromosomal replication, and the role of BRCA1 in DNA damage response, alongside downregulation of the cell cycle G1/S checkpoint, suggest that HCoV-229E may favors S phase for viral infection. Intriguingly, a significant portion of key factors of cell innate immunity, interferon-stimulated genes (ISGs) and other transcripts of early antiviral response genes were downregulated early in HCoV-229E infection. On the other hand, early upregulation of the antiviral response factor Apolipoprotein B mRNA editing enzyme catalytic subunit 3 B (APOBEC3B) was observed. APOBEC3B cytidine deaminase signature (C-to-T) was previously observed in genomic analysis of SARS-CoV-2 but not HCoV-229E. Higher levels of C-to-T mutations were found in countries with high mortality rates caused by SARS-CoV-2. APOBEC activity could be a marker for new emerging CoVs. This study will enhance our understanding of commonly circulating HCoVs and hopefully provide critical information about still-emerging coronaviruses.

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  1. Version published to 10.1371/journal.pone.0247128
  2. ScreenIT

    SciScore for 10.1101/2020.08.17.253682: (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
    RNA extraction and preparation: Total RNA was extracted at 0, 6, 24, 48, 72 and 96 hours post-HCoV-229E infection, using NucliSENS® easyMag®, according to the manufacturer’s protocol.
    NucliSENS®
    suggested: None
    Validation of gene expression was performed using SensiFAST™
    SensiFAST™
    suggested: None
    Software and applications used for sequencing and data analysis were as follows: library quality control: FASTQC version 0.11.5, quality and adapter trimming: trim_galore (uses cutadapt version 1.10),
    FASTQC
    suggested: (FastQC, RRID:SCR_014583)
    Tophat2 version 2.1.0 (uses Bowtie2 version 2.2.6), gene counting: HTseq-count version 0.6.1/0.11.2, normalization and differential expression analysis: DESeq2 R package version 1.18.1.
    Bowtie2
    suggested: (Bowtie 2, RRID:SCR_016368)
    HTseq-count
    suggested: (htseq-count, RRID:SCR_011867)
    DESeq2
    suggested: (DESeq, RRID:SCR_000154)
    RNA-Seq library is available at the Gene Expression Omnibus (GEO) repository, accession number GSE155986.
    Gene Expression Omnibus
    suggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)
    Data analysis was performed using QIAGEN Ingenuity Pathway Analysis (QIAGEN IPA)
    QIAGEN Ingenuity Pathway Analysis
    suggested: None
    Ingenuity
    suggested: (Ingenuity Pathway Analysis, RRID:SCR_008653)

    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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    About SciScore

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  3. Version published to 10.1101/2020.08.17.253682v1 on bioRxiv