RIG-I Recognizes the 5′ Region of Dengue and Zika Virus Genomes

被引：89

作者：

Chazal, Maxime ^{[1
,2
,3
]}

Beauclair, Guillaume ^{[1
]}

Gracias, Segolene ^{[1
]}

Najburg, Valerie ^{[1
]}

Simon-Loriere, Etienne ^{[2
,3
]}

Tangy, Frederic ^{[1
]}

Komarova, Anastassia V. ^{[1
]}

Jouvenet, Nolwenn ^{[1
]}

机构：

[1] Inst Pasteur, Unite Genom Virale & Vaccinat, Dept Virol, CNRS,UMR 3569, F-75015 Paris, France

[2] Inst Pasteur, Unite Genet Fonct Malad Infect, F-75015 Paris, France

[3] Inst Pasteur, CNRS, UMR2000, Genom Evolut Modelisat & Sante, F-75015 Paris, France

来源：

CELL REPORTS | 2018年 / 24卷 / 02期

基金：

欧盟地平线“2020”;

关键词：

RNA VIRUSES; MDA5; REPLICATION; ACTIVATION; ROLES; CELLS; PICORNAVIRUS; RECEPTORS; INFECTION; IMMUNITY;

D O I：

10.1016/j.celrep.2018.06.047

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The flavivirus genus comprises major human pathogens, such as Dengue (DENV) and Zika (ZIKV) viruses. RIG-I and MDA5 are key cytoplasmic pathogen recognition receptors that are implicated in detecting viral RNAs. Here, we show that RNAs that co-purified with RIG-I during DENV infection are immuno-stimulatory, whereas RNAs bound to MDA5 are not. An affinity purification method combined with next-generation sequencing (NGS) revealed that the 5' region of the DENV genome is recognized by RIG-I. No DENV RNA was bound to MDA5. In vitro production of fragments of the DENV genome confirmed the NGS data and revealed that the 5' end of the genome, when bearing 5'-triphosphates, is the RIG-I ligand. The 5' region of the ZIKV genome is also a RIG-I agonist. We propose that RIG-I binds to the highly structured and conserved 5' region of flavivirus nascent transcripts before capping and that this mechanism leads to interferon secretion by infected cells.

引用

页码：320 / 328

页数：9

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