Endosomal NOX2 oxidase exacerbates virus pathogenicity and is a target for antiviral therapy
File Type:
PDFItem Type:
Journal ArticleDate:
2017Access:
openAccessCitation:
To, E.E. and Vlahos, R. and Luong, R. and Halls, M.L. and Reading, P.C. and King, P.T. and Chan, C. and Drummond, G.R. and Sobey, C.G. and Broughton, B.R.S. and Starkey, M.R. and Van Der Sluis, R. and Lewin, S.R. and Bozinovski, S. and O'Neill, L.A.J. and Quach, T. and Porter, C.J.H. and Brooks, D.A. and O'Leary, J.J. and Selemidis, S., Endosomal NOX2 oxidase exacerbates virus pathogenicity and is a target for antiviral therapy, Nature Communications, 8, 1, 2017Download Item:
s41467-017-00057-x.pdf (PDF) 2.878Mb
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 de
fi
ned. 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
modi
fi
cation of a unique, highly conserved cysteine residue (Cys98) on Toll-like receptor-7.
Accordingly, targeted inhibition of endosomal reactive oxygen species production abrogates
in
fl
uenza A virus pathogenicity. We conclude that endosomal reactive oxygen species
promote fundamental molecular mechanisms of viral pathogenicity, and the speci
fi
c targeting
of this pathogenic process with endosomal-targeted reactive oxygen species inhibitors has
implications for the treatment of viral disease
Author's Homepage:
http://people.tcd.ie/laoneillhttp://people.tcd.ie/olearyjj
Description:
PUBLISHEDcited By 1
Author: O'NEILL, LUKE; O'LEARY, JOHN
Type of material:
Journal ArticleCollections:
Series/Report no:
Nature Communications8
1
Availability:
Full text availableKeywords:
viral epidemicsDOI:
http://dx.doi.org/10.1038/s41467-017-00057-xLicences: