GSTDTAP  > 资源环境科学
DOI10.1038/s41467-018-04311-8
Endosomal NOX2 oxidase exacerbates virus pathogenicity and is a target for antiviral therapy
To, Eunice E.1; 39;Neill, Luke A. J.2; 39;Leary, John J.3
2017-07-12
发表期刊NATURE COMMUNICATIONS
ISSN2041-1723
出版年2017
卷号8
文章类型Article
语种英语
国家Australia; USA; Ireland
英文摘要

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.


领域资源环境
收录类别SCI-E
WOS记录号WOS:000405269700002
WOS关键词INFLUENZA-A VIRUS ; NADPH OXIDASES ; OXIDATIVE STRESS ; DISEASE ; RECOGNITION ; RESPONSES ; ROS ; FAMILY
WOS类目Multidisciplinary Sciences
WOS研究方向Science & Technology - Other Topics
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文献类型期刊论文
条目标识符http://119.78.100.173/C666/handle/2XK7JSWQ/203814
专题资源环境科学
作者单位1.RMIT Univ, Coll Sci Engn & Hlth, Sch Hlth & Biomed Sci, Program Chron Infect & Inflammatory Dis, Bundoora, Vic 3083, Australia;
2.Monash Univ, Biomed Discovery Inst, Dept Pharmacol, Infect & Immun Program, Clayton, Vic 3800, Australia;
3.Monash Univ, Monash Inst Pharmaceut Sci, Drug Discovery Biol, Parkville, Vic 3052, Australia;
4.Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Melbourne, Vic 3000, Australia;
5.Monash Univ, Monash Med Ctr, Dept Med, Monash Lung & Sleep, Clayton, Vic 3168, Australia;
6.Massachusetts Gen Hosp, Harvard Med Sch, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA;
7.La Trobe Univ, Sch Life Sci, Dept Physiol Anat & Microbiol, Melbourne, Vic 3086, Australia;
8.Univ Newcastle, Fac Hlth & Med, Sch Biomed Sci & Pharm, Prior Res Centres Grow Well & Healthy Lungs, Newcastle, NSW 2305, Australia;
9.Hunter Med Res Inst, Newcastle, NSW 2305, Australia;
10.Univ Melbourne, Peter Doherty Inst Infect & Immun, Melbourne, Vic 3000, Australia;
11.Royal Melbourne Hosp, Melbourne, Vic 3000, Australia;
12.Alfred Hosp, Dept Infect Dis, Melbourne, Vic 3004, Australia;
13.Monash Univ, Melbourne, Vic 3004, Australia;
14.Trinity Coll Dublin, Trinity Biomed Sci Inst, Sch Biochem & Immunol, Dublin 2, Ireland;
15.Monash Univ, Monash Inst Pharmaceut Sci, ARC Ctr Excellence Convergent Bionano Sci & Techo, Parkville, Vic 3052, Australia;
16.Monash Univ, Monash Inst Pharmaceut Sci, Med Chem, Parkville, Vic 3052, Australia;
17.Monash Univ, Monash Inst Pharmaceut Sci, Drug Delivery Disposit & Dynam, Parkville, Vic 3052, Australia;
18.Univ South Australia, Div Hlth Sci, Sansom Inst Hlth Res, Sch Pharm & Med Sci, Adelaide, SA 5001, Australia;
19.Trinity Coll Dublin, TTMI, Sch Med, Discipline Histopathol, Dublin, Ireland;
20.St James Hosp, Cent Pathol Lab, Patrick Duns Lab, Dublin 8, Ireland;
21.Coombe Women & Infants Univ Hosp, Mol Pathol Lab, Dublin 8, Ireland
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To, Eunice E.,39;Neill, Luke A. J.,39;Leary, John J.. Endosomal NOX2 oxidase exacerbates virus pathogenicity and is a target for antiviral therapy[J]. NATURE COMMUNICATIONS,2017,8.
APA To, Eunice E.,39;Neill, Luke A. J.,&39;Leary, John J..(2017).Endosomal NOX2 oxidase exacerbates virus pathogenicity and is a target for antiviral therapy.NATURE COMMUNICATIONS,8.
MLA To, Eunice E.,et al."Endosomal NOX2 oxidase exacerbates virus pathogenicity and is a target for antiviral therapy".NATURE COMMUNICATIONS 8(2017).
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