S100A8 and S100A9, biomarkers of SARS-Cov2-infected patients, suppress HIV replication in primary macrophages

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Abstract

S100A8 and S100A9 are members of the Alarmin family; these proteins are abundantly expressed in neutrophils and form a heterodimer complex. Recently, both proteins were identified as novel biomarkers of SARS-CoV-2 infection and were shown to play key roles in inducing an aggressive inflammatory response by mediating the release of large amounts of pro-inflammatory cytokines, called the “cytokine storm.” Although co-infection with SARS-CoV-2 in people living with HIV-1 may result in an immunocompromised status, the role of the S100A8/A9 complex in HIV-1 replication in primary T cells and macrophages is still unclear. Here, we evaluated the roles of the proteins in HIV replication to elucidate their functions. We found that the complex had no impact on virus replication in both cell types; however, the subunits of S100A8 and S100A9 inhibits HIV in macrophages. These findings provide important insights into the regulation of HIV viral loads in SARS-CoV2 co-infection.

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  1. SciScore for 10.1101/2021.10.20.464686: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Cells and Reagents: Peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood of healthy donors as previously described [20], after we obtained approval from the National Institute of Allergy and Infectious Diseases Institutional Review Board.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Anti-SPTBN and anti-b-actin antibodies were obtained from Abcam (Waltham, MA, USA) and Sigma Aldrich, respectively.
    Anti-SPTBN
    suggested: None
    anti-b-actin
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    HIV replication assay: The HIV stocks of X4 (HIVNL4.3) [21] and R5 (HIVAD8) [22] viruses were prepared by transfection of the plasmid encoding each HIV strain into HEK293T cells, and the viruses were then purified from culture supernatants of the transfected cells using ultracentrifugation with 20% sucrose at 100,000 × g for 2h and infectious titers were determined by the endpoint assay as previously described [23].
    HEK293T
    suggested: None
    Recombinant DNA
    SentencesResources
    To obtain absolute proviral DNA copy numbers, standard curves were generated using serial dilutions of a plasmid encoding HIV gag region (pHIVgag) and RNaseP gene (pRNaseP) as previously described [24,25].
    pRNaseP
    suggested: None
    Software and Algorithms
    SentencesResources
    The intensity of the bands was analyzed by NIH Image J (http://rsbweb.nih.gov/ij/).
    Image J
    suggested: (ImageJ, RRID:SCR_003070)
    Statistical analysis: Statistical analysis was performed using the Analysis ToolPak from Microsoft Excel.
    Microsoft Excel
    suggested: (Microsoft Excel, RRID:SCR_016137)

    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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).


    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.

    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.