Endosomal NOX2 oxidase exacerbates virus pathogenicity and is a target for antiviral therapy.
Endosomal NOX2 oxidase exacerbates virus pathogenicity and is a target for antiviral therapy.
复制标题
内体NOX2氧化酶加剧病毒致病性，是抗病毒药疗法的靶标。
DOI：
10.1038/s41467-017-00057-x
复制
发表时间：
2017-07-12
影响因子：
16.6
通讯作者：
Selemidis S
中科院分区：
文献类型：
--
作者：
To EE;Vlahos R;Luong R;Halls ML;Reading PC;King PT;Chan C;Drummond GR;Sobey CG;Broughton BRS;Starkey MR;van der Sluis R;Lewin SR;Bozinovski S;O'Neill LAJ;Quach T;Porter CJH;Brooks DA;O'Leary JJ;Selemidis S
病毒流行和大流行的迫在眉睫的威胁要求采取针对病毒病理的治疗方法，而不考虑感染病毒的毒株。活性氧是保护植物、真菌和动物免受包括细菌在内的病原体入侵的古老过程。然而，在哺乳动物中，活性氧的产生矛盾地促进了病毒的致病作用，其机制尚不清楚。在这里，我们确定了活性氧物种的主要酶来源，NOX2氧化酶，是由内细胞室中的单链RNA和DNA病毒激活的，导致内体产生过氧化氢，通过修饰Toll样受体-7上唯一的高度保守的半胱氨酸残基(Cys98)来抑制抗病毒和体液信号网络。因此，有针对性地抑制内体活性氧的产生可以消除甲型流感病毒的致病性。我们的结论是，内体内的活性氧促进了病毒致病的基本分子机制，用内体靶向的活性氧抑制物特异性地靶向这一致病过程对于病毒疾病的治疗具有重要意义。产生活性氧是一种古老的抗微生物机制，但它在哺乳动物抗病毒防御中的作用尚不清楚。在这里，致等人。结果表明，病毒感染激活了内体NOX2氧化酶并限制了TLR7信号，内体NOX2抑制剂降低了病毒的致病性。
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. Production of reactive oxygen species is an ancient antimicrobial mechanism, but its role in antiviral defense in mammals is unclear. Here, To et al. show that virus infection activates endosomal NOX2 oxidase and restricts TLR7 signaling, and that an endosomal NOX2 inhibitor decreases viral pathogenicity.
登录
查看更多内容
DOI：
10.1038/nri3665
发表时间：
2014-05
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
120.1
作者：
Drummond, Grant R.;Selemidis, Stavros;Griendling, Kathy K.;Sobey, Christopher G.
通讯作者：
Sobey, Christopher G.
影响因子：
15.3
作者：
Ichinohe, Takeshi;Lee, Heung Kyu;Ogura, Yasunori;Flavell, Richard;Iwasaki, Akiko
通讯作者：
Iwasaki, Akiko
DOI：
10.1083/jcb.200302125
发表时间：
2003-06-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Violin JD;Zhang J;Tsien RY;Newton AC
通讯作者：
Newton AC
影响因子：
6.6
作者：
Mishina, Natalia M.;Tyurin-Kuzmin, Pyotr A.;Belousov, Vsevolod V.
通讯作者：
Belousov, Vsevolod V.