TRIM25 and ZAP target the Ebola virus ribonucleoprotein complex to mediate interferon-induced restriction.
TRIM25 and ZAP target the Ebola virus ribonucleoprotein complex to mediate interferon-induced restriction.
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DOI：
10.1371/journal.ppat.1010530
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发表时间：
2022-05
期刊：
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
--
作者：
埃博拉病毒(EBOV)在灵长类动物中引起高致病性疾病。通过筛选人干扰素刺激基因(ISGs)文库，我们确定TRIM25是EBOV转录和复制能力病毒样颗粒(TrVLP)复制的有效抑制因子。TRIM25的过表达抑制了病毒基因组和信使RNA的积累，而不依赖于RNA传感器RIG-I或次级促炎基因的表达。TRIM25的缺失显著降低了trVLP对I型干扰素抑制的敏感性。TRIM25的抗病毒活性需要ZAP，而I型干扰素的作用受病毒基因组中CpG二核苷酸含量的调节。我们发现TRIM25与EBOV vRNP相互作用，导致病毒核蛋白(NP)的自素化和泛素化。TRIM25在细胞进入后不久就被招募到传入的vRNP中，并导致NP从vRNA中解离。我们建议TRIM25以EBOV vRNP为靶点，使CpG丰富的病毒RNA物种受到ZAP的限制。作为早期宿主抗病毒防御的一部分，模式识别受体(PRRs)可以感知诸如埃博拉病毒(EBOV)之类的RNA病毒。PRR激活触发信号级联反应，导致I型干扰素(IFN)的表达，并随后上调数百个干扰素刺激基因(ISGs)，其中许多基因对病毒复制具有直接抑制活性。在这里，我们确定E3泛素连接酶TRIM25是一种ISG，可以有效地对抗EBOV转录和复制能力强的病毒样颗粒(TrVLP)系统的复制。我们证明了TRIM25与传入EBOV基因组相关的病毒蛋白相互作用，促进病毒核蛋白(NP)的泛素化及其与病毒RNA的解离。我们发现，TRIM25有助于干扰素介导的抗病毒作用，抑制EBOV的trVLP复制，这依赖于另一种ISG蛋白，ZAP，它针对病毒基因组中的CpG二核苷酸。我们建议TRIM25以EBOV病毒核糖核蛋白为靶点，以解离这一结构，并使病毒基因组暴露于ZAP的抗病毒功能中，以限制病毒复制。
Ebola virus (EBOV) causes highly pathogenic disease in primates. Through screening a library of human interferon-stimulated genes (ISGs), we identified TRIM25 as a potent inhibitor of EBOV transcription-and-replication-competent virus-like particle (trVLP) propagation. TRIM25 overexpression inhibited the accumulation of viral genomic and messenger RNAs independently of the RNA sensor RIG-I or secondary proinflammatory gene expression. Deletion of TRIM25 strongly attenuated the sensitivity of trVLPs to inhibition by type-I interferon. The antiviral activity of TRIM25 required ZAP and the effect of type-I interferon was modulated by the CpG dinucleotide content of the viral genome. We find that TRIM25 interacts with the EBOV vRNP, resulting in its autoubiquitination and ubiquitination of the viral nucleoprotein (NP). TRIM25 is recruited to incoming vRNPs shortly after cell entry and leads to dissociation of NP from the vRNA. We propose that TRIM25 targets the EBOV vRNP, exposing CpG-rich viral RNA species to restriction by ZAP. As part of the early host antiviral defence, RNA viruses such as Ebola Virus (EBOV) are sensed by pattern recognitions receptors (PRRs). PRR activation triggers signalling cascades that lead to the expression of type-I interferons (IFN), and the subsequent upregulation of hundreds of IFN-stimulated genes (ISGs), many of which have direct inhibitory activity on viral replication. Here we identified the E3 Ubiquitin-Ligase TRIM25 as an ISG potently antiviral against the replication of an EBOV transcription-and-replication-competent virus-like particle (trVLP) system. We demonstrated that TRIM25 interacts with viral proteins associated with incoming EBOV genome, promoting the ubiquitination of the viral nucleoprotein (NP), and its dissociation from the viral RNA. We showed that TRIM25 contributes for the IFN-mediated antiviral inhibition EBOV trVLP replication, and that this is dependent on another ISG protein, ZAP, which targets CpG dinucleotides in the viral genome. We suggest that TRIM25 targets the EBOV viral ribonucleoprotein in order to dissociate this structure and exposing the viral genome to the antiviral function of ZAP to limit viral replication.
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DOI：
10.1042/bj20121425
发表时间：
2013-12-01
期刊：
The Biochemical journal
影响因子：
--
作者：
D'Cruz AA;Kershaw NJ;Chiang JJ;Wang MK;Nicola NA;Babon JJ;Gack MU;Nicholson SE
通讯作者：
Nicholson SE
朊病毒样聚合是抗病毒免疫防御和炎症小体激活中信号转导的基础。
影响因子：
64.5
作者：
Cai X;Chen J;Xu H;Liu S;Jiang QX;Halfmann R;Chen ZJ
通讯作者：
Chen ZJ
影响因子：
6.7
作者：
Chiu HP;Chiu H;Yang CF;Lee YL;Chiu FL;Kuo HC;Lin RJ;Lin YL
通讯作者：
Lin YL
DOI：
10.1056/nejmoa1511410
发表时间：
2017-10-12
期刊：
The New England journal of medicine
影响因子：
--
作者：
Deen GF;Broutet N;Xu W;Knust B;Sesay FR;McDonald SLR;Ervin E;Marrinan JE;Gaillard P;Habib N;Liu H;Liu W;Thorson AE;Yamba F;Massaquoi TA;James F;Ariyarajah A;Ross C;Bernstein K;Coursier A;Klena J;Carino M;Wurie AH;Zhang Y;Dumbuya MS;Abad N;Idriss B;Wi T;Bennett SD;Davies T;Ebrahim FK;Meites E;Naidoo D;Smith SJ;Ongpin P;Malik T;Banerjee A;Erickson BR;Liu Y;Liu Y;Xu K;Brault A;Durski KN;Winter J;Sealy T;Nichol ST;Lamunu M;Bangura J;Landoulsi S;Jambai A;Morgan O;Wu G;Liang M;Su Q;Lan Y;Hao Y;Formenty P;Ströher U;Sahr F
通讯作者：
Sahr F
影响因子：
64.8
作者：
Cote, Marceline;Misasi, John;Ren, Tao;Bruchez, Anna;Lee, Kyungae;Filone, Claire Marie;Hensley, Lisa;Li, Qi;Ory, Daniel;Chandran, Kartik;Cunningham, James
通讯作者：
Cunningham, James