Preference of RIG-I for short viral RNA molecules in infected cells revealed by next-generation sequencing

被引:327
作者
Baum, Alina [1 ]
Sachidanandam, Ravi [4 ]
Garcia-Sastre, Adolfo [1 ,2 ,3 ]
机构
[1] Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA
[2] Mt Sinai Sch Med, Dept Med, Div Infect Dis, New York, NY 10029 USA
[3] Mt Sinai Sch Med, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA
[4] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA
基金
美国国家卫生研究院;
关键词
Sendai; influenza; interferon; pathogen-associated molecular pattern; defective-interfering particle; HEPATITIS-C VIRUS; DEFECTIVE INTERFERING PARTICLES; ANTIVIRAL INNATE IMMUNITY; DOUBLE-STRANDED-RNA; INDUCIBLE GENE-I; 5'-TRIPHOSPHATE RNA; ADAPTER PROTEIN; RECOGNITION; ACTIVATION; RESPONSES;
D O I
10.1073/pnas.1005077107
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Intracellular detection of virus infections is a critical component of innate immunity carried out by molecules known as pathogen recognition receptors (PRRs). Activation of PRRs by their respective pathogen-associated molecular patterns (PAMPs) leads to production of proinflamatory cytokines, including type I IFN, and the establishment of an antiviral state in the host. Out of all PRRs found to date, retinoic acid inducible gene I (RIG-I) has been shown to play a key role in recognition of RNA viruses. On the basis of in vitro and transfection studies, 5'ppp RNA produced during virus replication is thought to bind and activate this important sensor. However, the nature of RNA molecules that interact with endogenous RIG-I during the course of viral infection has not been determined. In this work we use next-generation RNA sequencing to show that RIG-I preferentially associates with shorter, 5'ppp containing viral RNA molecules in infected cells. We found that during Sendai infection RIG-I specifically bound the genome of the defective interfering (DI) particle and did not bind the full-length virus genome or any other viral RNAs. In influenza-infected cells RIG-I preferentially associated with shorter genomic segments as well as subgenomic DI particles. Our analysis for the first time identifies RIG-I PAMPs under natural infection conditions and implies that full-length genomes of single segmented RNA virus families are not bound by RIG-I during infection.
引用
收藏
页码:16303 / 16308
页数:6
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