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Endosomal NOX2 oxidase exacerbates virus pathogenicity and is a target for antiviral therapy

Author

Listed:
  • Eunice E. To

    (School of Health and Biomedical Sciences, College of Science, Engineering & Health, RMIT University
    Monash University)

  • Ross Vlahos

    (School of Health and Biomedical Sciences, College of Science, Engineering & Health, RMIT University)

  • Raymond Luong

    (Monash University)

  • Michelle L. Halls

    (Monash University)

  • Patrick C. Reading

    (The University of Melbourne, The Peter Doherty Institute for Infection and Immunity)

  • Paul T. King

    (Monash University)

  • Christopher Chan

    (Monash University
    Harvard Medical School, 185 Cambridge Street)

  • Grant R. Drummond

    (School of Life Sciences, La Trobe University)

  • Christopher G. Sobey

    (School of Life Sciences, La Trobe University)

  • Brad R. S. Broughton

    (Monash University)

  • Malcolm R. Starkey

    (The University of Newcastle, and Hunter Medical Research Institute)

  • Renee van der Sluis

    (The University of Melbourne and Royal Melbourne Hospital)

  • Sharon R. Lewin

    (The University of Melbourne and Royal Melbourne Hospital
    Alfred Hospital and Monash University)

  • Steven Bozinovski

    (School of Health and Biomedical Sciences, College of Science, Engineering & Health, RMIT University)

  • Luke A. J. O’Neill

    (Trinity College Dublin)

  • Tim Quach

    (Monash University
    Monash University
    Monash University)

  • Christopher J. H. Porter

    (Monash University
    Monash University)

  • Doug A. Brooks

    (University of South Australia)

  • John J. O’Leary

    (Trinity Translational Medicine Institute (TTMI)
    Central Pathology Laboratory, St James’s Hospital
    The Coombe Women and Infants University Hospital)

  • Stavros Selemidis

    (School of Health and Biomedical Sciences, College of Science, Engineering & Health, RMIT University
    Monash University)

Abstract

The imminent threat of viral epidemics and pandemics dictates a need for therapeutic approaches that target viral pathology irrespective of the infecting strain. Reactive oxygen species are ancient processes that protect plants, fungi and animals against invading pathogens including bacteria. However, in mammals reactive oxygen species production paradoxically promotes virus pathogenicity by mechanisms not yet defined. Here we identify that the primary enzymatic source of reactive oxygen species, NOX2 oxidase, is activated by single stranded RNA and DNA viruses in endocytic compartments resulting in endosomal hydrogen peroxide generation, which suppresses antiviral and humoral signaling networks via modification of a unique, highly conserved cysteine residue (Cys98) on Toll-like receptor-7. Accordingly, targeted inhibition of endosomal reactive oxygen species production abrogates influenza A virus pathogenicity. We conclude that endosomal reactive oxygen species promote fundamental molecular mechanisms of viral pathogenicity, and the specific targeting of this pathogenic process with endosomal-targeted reactive oxygen species inhibitors has implications for the treatment of viral disease.

Suggested Citation

  • Eunice E. To & Ross Vlahos & Raymond Luong & Michelle L. Halls & Patrick C. Reading & Paul T. King & Christopher Chan & Grant R. Drummond & Christopher G. Sobey & Brad R. S. Broughton & Malcolm R. Sta, 2017. "Endosomal NOX2 oxidase exacerbates virus pathogenicity and is a target for antiviral therapy," Nature Communications, Nature, vol. 8(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00057-x
    DOI: 10.1038/s41467-017-00057-x
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    Cited by:

    1. Gang Liu & Tatt Jhong Haw & Malcolm R. Starkey & Ashleigh M. Philp & Stelios Pavlidis & Christina Nalkurthi & Prema M. Nair & Henry M. Gomez & Irwan Hanish & Alan CY. Hsu & Elinor Hortle & Sophie Pick, 2023. "TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase," Nature Communications, Nature, vol. 14(1), pages 1-24, December.

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