VPS29 Exerts Opposing Effects on Endocytic Viral Entry

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Abstract

These data identify a host pathway by which VPS29 and associated factors control the endosomal environment in a manner that influences susceptibility to viral infection. This pathway could serve as a pharmaceutical target for intervention in zoonotic viral diseases, including those caused by coronaviruses, influenza viruses, and filoviruses, all of which are pandemic threats.

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  1. SciScore for 10.1101/2021.08.06.455441: (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.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Briefly, cells were blocked with 5.0% fetal bovine serum in PBS and permeabilized with 0.5% Saponin before a 30 minutes incubation with: HCoV-OC43: Anti-Coronavirus Group Antigen Antibody, nucleoprotein of OC-43 (1:1000, Sigma MAB9013);
    Anti-Coronavirus Group Antigen Antibody , nucleoprotein of OC-43
    suggested: None
    48 hours post transduction, cells were fixed in 4% PFA, permeabilized with 0.1% triton, blocked with FBS and stained for V5 (invitrogen cat# 46-0705, 1:1000) and antibody conjugate AF-488 Goat anti-Mouse IgG (H+L) (Thermo, 1:1000).
    V5
    suggested: None
    anti-Mouse IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    To generate lentiviral preparations of the Brunello library, 293T cells (6 × 106 cells per 10 cm dish) were transfected with 6µg lentiCRISPRv2-Brunello, 6µg NL-gagpol, and 1.2 µg VSV-G using PEI. 48 hours post transfection, supernatants were pooled and concentrated using Amicon Ultra Centrifugal Filters
    293T
    suggested: None
    Briefly, 10-fold serial dilutions (from 10−1 to 10−6) were used to transduce 40,000 A549 cells in a 24 well plate format.
    A549
    suggested: None
    Thereafter, in triplicates with 8×106 cells per flask, A549-Brunello cells were infected or not with HCoV-OC43 at an MOI of 0.1, and passaged for 7 days until >95% infection-induced cell death occurred.
    A549-Brunello
    suggested: None
    Recombinant DNA
    SentencesResources
    The next day, 7.5 µg pHIV-1NL4-3 ΔEnv-NanoLuc and 2.5 µg indicated CoV spike plasmid were transfected using PEI.
    pHIV-1NL4-3
    suggested: None
    Software and Algorithms
    SentencesResources
    Pathway Analysis of screen hits: All 34 candidate genes were searched using the STRING database (https://string-db.org) for functional enrichment of protein-protein interactions using default settings, except the minimum required interaction score was changed from medium confidence (0.400) to high confidence (0.700).
    STRING
    suggested: (STRING, RRID:SCR_005223)
    Quantification of fluorescence microscopy: For each cell, Regions Of Interest (ROIs) corresponding to labeled endosomes were defined using the freehand selection tool in Fiji.
    Fiji
    suggested: (Fiji, RRID:SCR_002285)

    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: Please consider improving the rainbow (“jet”) colormap(s) used on pages 17 and 33. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.


    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.