RRC ID 74418
著者 Arai Y, Yamanaka I, Okamoto T, Isobe A, Nakai N, Kamimura N, Suzuki T, Daidoji T, Ono T, Nakaya T, Matsumoto K, Okuzaki D, Watanabe Y.
タイトル Stimulation of interferon-β responses by aberrant SARS-CoV-2 small viral RNAs acting as retinoic acid-inducible gene-I agonists.
ジャーナル iScience
Abstract Patients with severe COVID-19 exhibit a cytokine storm characterized by greatly elevated levels of cytokines. Despite this, the interferon (IFN) response is delayed, contributing to disease progression. Here, we report that SARS-CoV-2 excessively generates small viral RNAs (svRNAs) encoding exact 5' ends of positive-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 5' end svRNAs are RIG-I agonists and induce the IFN-β response in the later stages of infection. The first 60-nt ends bearing duplex structures and 5'-triphosphates are responsible for immune-stimulation. We propose that RIG-I activation by accumulated SARS-CoV-2 5' 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.
巻・号 26(1)
ページ 105742
公開日 2023-1-20
DOI 10.1016/j.isci.2022.105742
PII S2589-0042(22)02015-6
PMID 36507221
PMC PMC9726650
IF 4.447
リソース情報
ヒト・動物細胞 293T(RCB2202) Vero(RCB0001)