Stimulation of interferon-b responses by aberrant SARS-CoV-2 small viral RNAs acting as retinoic acid-inducible gene-I agonists

被引：5

作者：

Arai, Yasuha

Yamanaka, Itaru ^{[2
]}

Okamoto, Toru ^{[3
]}

Isobe, Ayana ^{[1
]}

Nakai, Naomi ^{[2
]}

Kamimura, Naoko ^{[2
]}

Suzuki, Tatsuya ^{[3
]}

Daidoji, Tomo ^{[1
]}

Ono, Takao ^{[4
]}

Nakaya, Takaaki ^{[1
]}

Matsumoto, Kazuhiko ^{[4
]}

Okuzaki, Daisuke ^{[2
,5
]}

Watanabe, Yohei ^{[1
]}

机构：

[1] Kyoto Prefectural Univ Med, Dept Infect Dis, Kyoto 6028566, Japan

[2] Osaka Univ, Res Inst Microbial Dis, Genome Informat Res Ctr, Osaka 5650871, Japan

[3] Osaka Univ, Inst Adv Cocreat Studies, Res Inst Microbial Dis, Osaka 5650871, Japan

[4] Osaka Univ, SANKEN, Osaka 5670047, Japan

[5] Osaka Univ, WPI Immunol Frontier Res Ctr, Single Cell Genom, Human Immunol, Osaka 5650871, Japan

来源：

ISCIENCE | 2023年 / 26卷 / 01期

关键词：

RIG-I; VIRUS; TRANSCRIPTION; INFECTION; REGION; HIV-1;

D O I：

10.1016/j.isci.2022.105742

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：

Patients with severe COVID-19 exhibit a cytokine storm characterized by greatly elevated levels of cytokines. Despite this, the interferon (IFN) response is de-layed, contributing to disease progression. Here, we report that SARS-CoV-2 excessively generates small viral RNAs (svRNAs) encoding exact 50 ends of posi-tive-sense genes in human cells in vitro and ex vivo, whereas endemic human coronaviruses (OC43 and 229E) produce significantly fewer similar svRNAs. SARS-CoV-2 50 end svRNAs are RIG-I agonists and induce the IFN-b response in the later stages of infection. The first 60-nt ends bearing duplex structures and 50-triphosphates are responsible for immune-stimulation. We propose that RIG-I activation by accumulated SARS-CoV-2 50 end svRNAs may contribute to later drive over-exuberant IFN production. Additionally, the differences in the amounts of svRNAs produced and the corresponding IFN response among CoV strains suggest that lower svRNA production during replication may correlate with the weaker immune response seen in less pathogenic CoVs.

引用

页数：28