Potential microenvironment of SARS-CoV-2 infection in airway epithelial cells revealed by Human Protein Atlas database analysis

  1. Ling Leng
  2. Jie Ma
  3. Leike Zhang
  4. Wei Li
  5. Lei Zhao
  6. Yunping Zhu
  7. Zhihong Wu
  8. Ruiyuan Cao
  9. Wu Zhong

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Abstract

The outbreak of COVID-19 has caused serious epidemic events in China and other countries. With the rapid spread of COVID-19, it is urgent to explore the pathogenesis of this novel coronavirus. However, the foundational research of COVID-19 is very weak. Although angiotensin converting enzyme 2 (ACE2) is the reported receptor of SARS-CoV-2, information about SARS-CoV-2 invading airway epithelial cells is very limited. Based on the analysis of the Human Protein Atlas database, we compared the virus-related receptors of epithelial-derived cells from different organs and found potential key molecules in the local microenvironment for SARS-CoV-2 entering airway epithelial cells. In addition, we found that these proteins were associated with virus reactive proteins in host airway epithelial cells, which may promote the activation of the immune system and the release of inflammatory factors. Our findings provide a new research direction for understanding the potential microenvironment required by SARS-CoV-2 infection in airway epithelial, which may assist in the discovery of potential drug targets against SARS-CoV-2 infection.

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  1. ScreenIT

    SciScore for 10.1101/2020.04.16.045799: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Data sources: Generally, the expression profiles of human genes on the protein level were derived from the Human Protein Atlas (HPA, https://www.proteinatlas.org/) [16].
    https://www.proteinatlas.org/
    suggested: (HPA, RRID:SCR_006710)
    All human protein annotations were downloaded from the Swiss-Prot database of UniProt (https://www.uniprot.org/) [18].
    https://www.uniprot.org/
    suggested: (Universal Protein Resource, RRID:SCR_002380)
    Then, after manually checking, only those terms related to host-virus receptor and key biological processes were taken (Table S2), and the human proteins involved in these particular GO terms were retrieved from UniProt database.
    UniProt
    suggested: (UniProtKB, RRID:SCR_004426)
    Data visualization: Heap map views of protein expression levels were displayed using conditional formatting of Microsoft Excel spreadsheets.
    Microsoft Excel
    suggested: (Microsoft Excel, RRID:SCR_016137)
    All protein-protein interactions were retrieved from the STRING database [19], and the protein-protein interaction network was built using Cytoscape software (version 3.7.1) [20].
    STRING
    suggested: (STRING, RRID:SCR_005223)
    Cytoscape
    suggested: (Cytoscape, RRID:SCR_003032)

    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: We detected the following sentences addressing limitations in the study:
    Thus, limitations arise when predicting protein expression based only on mRNA expression levels. In a clinical study of 41 patients, it was speculated that SARS-CoV-2 mainly infected the lower respiratory tract [7]. A Chinese research group also isolated this virus from airway EpCs [4, 8]. These results indicate that airway EpCs are possibly a susceptible and primary target for SARS-CoV-2. Furthermore, initial viral entrance may cause cytopathological changes to airway EpCs, resulting in coughing in 76% of patients [7] and further indicating that the lung is also susceptible to virus infection. Thus, the susceptibility of different organs to SARS-CoV-2 is not consistent with corresponding protein expression levels of ACE2 on these organs. We therefore asked (i) why SARS-CoV-2 infects the respiratory tract rather than other organs as its first target organ, (ii) what is the difference between airway EpCs and epithelial-derived cells of other organs, and (iii) whether specific local microenvironment components were required for SARS-CoV-2 infection besides ACE2 that are sufficient to compensate for the low expression of ACE2 in airway EpCs. To explore these issues, we first outlined the expression profile of virus receptors or receptor-related membrane proteins (collectively named virus microenvironment components) of EpCs located in different organs. We used the human protein atlas (HPA) database [16] to extract the protein expression level of 65 receptors involved in “virus r...

    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.

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  2. Version published to 10.1101/2020.04.16.045799v1 on bioRxiv