RNF115 plays dual roles in innate antiviral responses by catalyzing distinct ubiquitination of MAVS and MITA.
RNF115 plays dual roles in innate antiviral responses by catalyzing distinct ubiquitination of MAVS and MITA.
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DOI：
10.1038/s41467-020-19318-3
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发表时间：
2020-11-02
影响因子：
16.6
通讯作者：
Zhong B
中科院分区：
文献类型：
--
作者：
Zhang ZD;Xiong TC;Yao SQ;Wei MC;Chen M;Lin D;Zhong B
MAVS和MITA分别是介导针对RNA和DNA病毒的先天性抗病毒免疫应答的必需衔接蛋白。在这里，我们表明，RNF 115起着双重作用，在响应RNA或DNA病毒感染，催化不同类型的泛素化的MAVS和MITA在病毒感染的不同阶段。RNF 115在未感染的细胞中与稳态MAVS的K48连接的泛素化和蛋白酶体降解组成性相互作用并诱导其相互作用，而在HSV-1感染后与MITA的K63连接的泛素化相关联并催化其降解。一致的是，MAVS的蛋白水平在没有病毒感染的Rnf 115 −/−器官或细胞中显著增加，并且与野生型对应物相比，HSV-1诱导的MITA聚集在Rnf 115 −/−细胞中受损。因此，Rnf 115 −/−小鼠分别对EMCV和HSV-1感染表现出低敏感性和高敏感性。这些发现突出了RNF 115介导的MAVS和MITA泛素化对细胞抗病毒反应的双重调节，有助于我们理解先天免疫信号传导。MAVS和MITA是衔接蛋白，分别在宿主对RNA和DNA病毒的应答中发挥不同的作用。在这里，作者暗示RNF 115在相互作用和催化MAVS和MITA的不同泛素化以调节RNA和DNA抗病毒免疫应答的双重时空机制中。
MAVS and MITA are essential adaptor proteins mediating innate antiviral immune responses against RNA and DNA viruses, respectively. Here we show that RNF115 plays dual roles in response to RNA or DNA virus infections by catalyzing distinct types of ubiquitination of MAVS and MITA at different phases of viral infection. RNF115 constitutively interacts with and induces K48-linked ubiquitination and proteasomal degradation of homeostatic MAVS in uninfected cells, whereas associates with and catalyzes K63-linked ubiquitination of MITA after HSV-1 infection. Consistently, the protein levels of MAVS are substantially increased in Rnf115−/− organs or cells without viral infection, and HSV-1-induced aggregation of MITA is impaired in Rnf115−/− cells compared to the wild-type counterparts. Consequently, the Rnf115−/− mice exhibit hypo- and hyper-sensitivity to EMCV and HSV-1 infection, respectively. These findings highlight dual regulation of cellular antiviral responses by RNF115-mediated ubiquitination of MAVS and MITA and contribute to our understanding of innate immune signaling. MAVS and MITA are adapter proteins that play distinct roles in the context of the host response to RNA and DNA viruses, respectively. Here the authors implicate RNF115 in dual temporal and spatial mechanisms of interacting and catalyzing distinct ubiquitination of MAVS and MITA to modulate RNA and DNA antiviral immune responses.
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DOI：
10.1126/science.1244040
发表时间：
2013-09-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Li XD;Wu J;Gao D;Wang H;Sun L;Chen ZJ
通讯作者：
Chen ZJ
影响因子：
64.8
作者：
Meylan, E;Curran, J;Tschopp, R
通讯作者：
Tschopp, R
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DOI：
10.1073/pnas.1509968112
发表时间：
2015-09-08
影响因子：
11.1
作者：
Lin, Dandan;Zhang, Man;Zhong, Bo
通讯作者：
Zhong, Bo
影响因子：
30.5
作者：
Kawai, T;Takahashi, K;Akira, S
通讯作者：
Akira, S
影响因子：
5.4
作者：
Colomer-Lluch M;Serra-Moreno R
通讯作者：
Serra-Moreno R