USP44 positively regulates innate immune response to DNA viruses through deubiquitinating MITA
USP44 positively regulates innate immune response to DNA viruses through deubiquitinating MITA
复制标题
USP44 通过去泛素化 MITA 积极调节对 DNA 病毒的先天免疫反应
DOI：
10.1371/journal.ppat.1008178
复制
发表时间：
2020-01
期刊：
影响因子：
6.7
通讯作者：
Wang Yan-Yi
中科院分区：
文献类型：
--
作者：
Zhang Hong-Yan;Liao Bo-Wei;Xu Zhi-Sheng;Ran Yong;Wang Dong-Peng;Yang Yan;Luo Wei-Wei;Wang Yan-Yi
IRF 3激活介体（Mediator of IRF 3 activation，MITA，也称为干扰素基因刺激因子，STING）感测第二信使环GMP-AMP（cGAMP），其在DNA病毒感染时合成并激活先天性抗病毒免疫应答。研究表明，MITA的活性受到多种翻译后修饰（包括多聚泛素化）的精细调控。在这项研究中，我们确定了去泛素化酶USP 44作为MITA的正调节因子。DNA病毒感染后，USP 44被募集到MITA中，并在K236处从MITA中去除K48连接的多聚泛素部分，因此防止MITA被蛋白酶体介导的降解。USP 44缺陷导致HSV-1诱导的MITA降解加速，I型干扰素（IFN）和促炎细胞因子诱导减少。一致地，Usp 44-/-小鼠更易受HSV-1感染，如由更高的组织病毒滴度、更大的组织损伤和更低的存活率所指示的。这些发现表明USP 44在调节针对DNA病毒的先天免疫应答中起着特异性和关键性作用。
Mediator of IRF3 activation (MITA, also known as stimulator of interferon genes, STING) senses the second messenger cyclic GMP-AMP (cGAMP) which is synthesized upon DNA virus infection and activates innate antiviral immune response. It has been demonstrated that the activity of MITA is delicately regulated by various post-translational modifications including polyubiquitination. In this study, we identified the deubiquitinating enzyme USP44 as a positive regulator of MITA. USP44 is recruited to MITA following DNA virus infection and removes K48-linked polyubiquitin moieties from MITA at K236, therefore prevents MITA from proteasome mediated degradation. USP44-deficiency results in acceleration of HSV-1-induced degradation of MITA and reduced induction of type I interferons (IFNs) and proinflammatory cytokines. Consistently, Usp44-/- mice are more susceptible to HSV-1 infection as indicated by higher tissue viral titers, greater tissue damage and lower survival rate. These findings suggest that USP44 plays a specific and critical role in the regulation of innate immune response against DNA viruses.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
对 RNA 病毒的先天免疫受 RIG-I 和 MDA5 的暂时且可逆的 sumoylation 调节
DOI：
10.1084/jem.20161015
发表时间：
2017-04-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hu MM;Liao CY;Yang Q;Xie XQ;Shu HB
通讯作者：
Shu HB
影响因子：
16.6
作者：
Sun H;Zhang Q;Jing YY;Zhang M;Wang HY;Cai Z;Liuyu T;Zhang ZD;Xiong TC;Wu Y;Zhu QY;Yao J;Shu HB;Lin D;Zhong B
通讯作者：
Zhong B
影响因子：
7.7
作者：
Friedman, Constantin S.;O'Donnell, Marie Anne;Ting, Adrian T.
通讯作者：
Ting, Adrian T.
影响因子：
30.3
作者：
Zhou, Qian;Lin, Heng;Wang, Yan-Yi
通讯作者：
Wang, Yan-Yi