tetano
Editor, Senior Moderator
iScience
. 2022 Dec 7;105742.
doi: 10.1016/j.isci.2022.105742. Online ahead of print.
Stimulation of IFN-β responses by aberrant SARS-CoV-2 small viral RNAs acting as RIG-I agonists
Yasuha Arai[SUP] 1 [/SUP], Itaru Yamanaka[SUP] 2 [/SUP], Toru Okamoto[SUP] 3 [/SUP], Ayana Isobe[SUP] 1 [/SUP], Naomi Nakai[SUP] 2 [/SUP], Naoko Kamimura[SUP] 2 [/SUP], Tatsuya Suzuki[SUP] 3 [/SUP], Tomo Daidoji[SUP] 1 [/SUP], Takao Ono[SUP] 4 [/SUP], Takaaki Nakaya[SUP] 1 [/SUP], Kazuhiko Matsumoto[SUP] 4 [/SUP], Daisuke Okuzaki[SUP] 2 5 [/SUP], Yohei Watanabe[SUP] 1 [/SUP]
Affiliations
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 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.
Keywords: 5′ end small RNA; COVID-19; IFN induction; SARS-CoV-2; cytokine storm.
. 2022 Dec 7;105742.
doi: 10.1016/j.isci.2022.105742. Online ahead of print.
Stimulation of IFN-β responses by aberrant SARS-CoV-2 small viral RNAs acting as RIG-I agonists
Yasuha Arai[SUP] 1 [/SUP], Itaru Yamanaka[SUP] 2 [/SUP], Toru Okamoto[SUP] 3 [/SUP], Ayana Isobe[SUP] 1 [/SUP], Naomi Nakai[SUP] 2 [/SUP], Naoko Kamimura[SUP] 2 [/SUP], Tatsuya Suzuki[SUP] 3 [/SUP], Tomo Daidoji[SUP] 1 [/SUP], Takao Ono[SUP] 4 [/SUP], Takaaki Nakaya[SUP] 1 [/SUP], Kazuhiko Matsumoto[SUP] 4 [/SUP], Daisuke Okuzaki[SUP] 2 5 [/SUP], Yohei Watanabe[SUP] 1 [/SUP]
Affiliations
- PMID: 36507221
- PMCID: PMC9726650
- DOI: 10.1016/j.isci.2022.105742
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 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.
Keywords: 5′ end small RNA; COVID-19; IFN induction; SARS-CoV-2; cytokine storm.