Regulation of Lysosomal Associated Membrane Protein 3 (LAMP3) in Lung Epithelial Cells by Coronaviruses (SARS-CoV-1/2) and Type I Interferon Signaling

  1. Chilakamarti V. Ramana
  2. Bikul Das

Reviewed by

Read the full article See related articles

Discuss this preprint

Start a discussion What are Sciety discussions?

Listed in

Log in to save this article

Abstract

Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) infection is a major risk factor for mortality and morbidity in critical care hospitals around the world. Lung epithelial type II cells play a major role in the recognition and clearance of respiratory viruses as well as repair of lung injury in response to environmental toxicants. Gene expression profiling studies revealed that mouse lung epithelial type II cells express several cell-specific markers including surfactant proteins and Lysosomal associated membrane protein 3 (LAMP3) located in lysosomes, endosomes and lamellar bodies. These intracellular organelles are involved in vesicular transport and facilitate viral entry and release of the viral genome into the host cell cytoplasm. In this study, regulation of LAMP3 expression in human lung epithelial cells by several respiratory viruses and type I interferon signaling was investigated. Respiratory viruses including SARS-CoV-1 and SARS-CoV-2 significantly induced LAMP3 expression in lung epithelial cells within 24 hours after infection that required the presence of ACE2 viral entry receptors. Time course experiments revealed that the induced expression of LAMP3 was correlated with the induced expression of Interferon–beta (IFNB1) and STAT1 at mRNA levels. LAMP3 was also induced by direct IFN-beta treatment in multiple lung epithelial cell lines or by infection with influenza virus lacking the non-structural protein1(NS1) in NHBE bronchial epithelial cells. LAMP3 expression was also induced by several respiratory viruses in human lung epithelial cells including RSV and HPIV3. Location in lysosomes and endosomes aswell as induction by respiratory viruses and type I Interferon suggests that LAMP3 may have an important role in inter-organellar regulation of innate immunity and a potential target for therapeutic modulation in health and disease. Furthermore, bioinformatics revealed that a subset of lung type II genes were differentially regulated in the lungs of COVID-19 patients.

Article activity feed

  1. Version published to 10.1515/cmb-2022-0140
  2. ScreenIT

    SciScore for 10.1101/2021.04.28.441840: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Protein-protein interactions were visualized in BIOGRID or the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) databases (19,20)
    BIOGRID
    suggested: (BioGrid Australia, RRID:SCR_006334)
    STRING
    suggested: (STRING, RRID:SCR_005223)
    Gene ontology (GO) and transcription factor analysis were done in Metascape and TRANSFAC databases, respectively (21,22).
    Metascape
    suggested: (Metascape, RRID:SCR_016620)
    , TCGA cancer database, and GeneCards.
    GeneCards
    suggested: (GeneCards, RRID:SCR_002773)

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

    Results from scite Reference Check: We found no unreliable references.

    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 10.1101/2021.04.28.441840 on bioRxiv