- Title
- Endosomal NOX2 oxidase exacerbates virus pathogenicity and is a target for antiviral therapy
- Creator
- To, Eunice E.; Vlahos, Ross; Starkey, Malcolm R.; van der Sluis, Renee; Lewin, Sharon R.; Bozinovski, Steven; O'Neill, Luke A. J.; Quach, Tim; Porter, Christopher J. H.; Brooks, Doug A.; O'Leary, John J.; Selemidis, Stavros; Luong, Raymond; Halls, Michelle L.; Reading, Patrick C.; King, Paul T.; Chan, Christopher; Drummond, Grant R.; Sobey, Christopher G.; Broughton, Brad R. S.
- Relation
- Funding BodyNHMRCGrant Number1072000 http://purl.org/au-research/grants/nhmrc/1072000
- Relation
- Nature Communications Vol. 8, no. 69
- Publisher Link
- http://dx.doi.org/10.1038/s41467-017-00057-x
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2017
- Description
- 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.
- Subject
- viral pathology; viral epidemics; pandemics; reactive oxygen species; bacteria; NOX2 oxidase; antiviral therapy
- Identifier
- http://hdl.handle.net/1959.13/1397210
- Identifier
- uon:34211
- Identifier
- ISSN:2041-1723
- Rights
- © The Author(s) 2017. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.
- Language
- eng
- Full Text
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