{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:46:27Z","timestamp":1790405187310,"version":"4.1.0"},"reference-count":22,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T00:00:00Z","timestamp":1716768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-RS-2023-00273383"],"award-info":[{"award-number":["NRF-RS-2023-00273383"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The devastating effects of COVID-19 have highlighted the importance of prophylactic and therapeutic strategies to combat respiratory diseases. Stimulator of interferon gene (STING) is an essential component of the host defense mechanisms against respiratory viral infections. Although the role of the cGAS\/STING signaling axis in the innate immune response to DNA viruses has been thoroughly characterized, mounting evidence shows that it also plays a key role in the prevention of RNA virus infections. In this study, we investigated the role of STING activation during Influenza virus (IFV) infection. In both mouse bone marrow-derived macrophages and monocytic cell line THP-1 differentiated with PMA, we found that dimeric amidobenzimidazole (diABZI), a STING agonist, had substantial anti-IFV activity against multiple strains of IFV, including A\/H1N1, A\/H3N2, B\/Yamagata, and B\/Victoria. On the other hand, a pharmacological antagonist of STING (H-151) or the loss of STING in human macrophages leads to enhanced viral replication but suppressed IFN expression. Furthermore, diABZI was antiviral against IFV in primary air\u2013liquid interface cultures of nasal epithelial cells. Our data suggest that STING agonists may serve as promising therapeutic antiviral agents to combat IFV.<\/jats:p>","DOI":"10.3390\/v16060855","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T10:14:07Z","timestamp":1716804847000},"page":"855","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Stimulator of Interferon Gene Agonists Induce an Innate Antiviral Response against Influenza Viruses"],"prefix":"10.3390","volume":"16","author":[{"given":"Hyun Jung","family":"Lee","sequence":"first","affiliation":[{"name":"BK21 Graduate Program, Department of Biomedical Sciences, College of Medicine, Korea University Guro Hospital, Seoul 08308, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo-Hoo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul 08308, Republic of Korea"},{"name":"Upper Airway Chronic Inflammatory Diseases Laboratory, Korea University, Seoul 08308, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7011-6071","authenticated-orcid":false,"given":"Il-Ho","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul 08308, Republic of Korea"},{"name":"Upper Airway Chronic Inflammatory Diseases Laboratory, Korea University, Seoul 08308, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ok Sarah","family":"Shin","sequence":"additional","affiliation":[{"name":"BK21 Graduate Program, Department of Biomedical Sciences, College of Medicine, Korea University Guro Hospital, Seoul 08308, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,27]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2023, October 03). Global Influenza Surveillance and Response System (GISRS). Available online: https:\/\/www.who.int\/initiatives\/global-influenza-surveillance-and-response-system."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1038\/nri3921","article-title":"STING: Infection, inflammation and cancer","volume":"15","author":"Barber","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"104933","DOI":"10.1016\/j.antiviral.2020.104933","article-title":"A synthetic STING agonist inhibits the replication of human parainfluenza virus 3 and rhinovirus 16 through distinct mechanisms","volume":"183","author":"Zhu","year":"2020","journal-title":"J. Antivir. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-019-0333-0","article-title":"STING signaling and host defense against microbial infection","volume":"51","author":"Ahn","year":"2019","journal-title":"J. Exp. Mol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/s41586-018-0705-y","article-title":"Design of amidobenzimidazole STING receptor agonists with systemic activity","volume":"564","author":"Ramanjulu","year":"2018","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"105015","DOI":"10.1016\/j.antiviral.2021.105015","article-title":"Inhibition of coronavirus infection by a synthetic STING agonist in primary human airway system","volume":"187","author":"Zhu","year":"2021","journal-title":"Antivir. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101024","DOI":"10.1016\/j.xcrm.2023.101024","article-title":"Innate immune pathway modulator screen identifies STING pathway activation as a strategy to inhibit multiple families of arbo and respiratory viruses","volume":"4","author":"Garcia","year":"2023","journal-title":"Cell Rep. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e40","DOI":"10.4110\/in.2019.19.e40","article-title":"Zika Virus Impairs Host NLRP3-mediated Inflammasome Activation in an NS3-dependent Manner","volume":"19","author":"Gim","year":"2019","journal-title":"Immune Netw."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Oh, S.J., Lee, E.N., Park, J.H., Lee, J.K., Cho, G.J., Park, I.H., and Shin, O.S. (2022). Anti-Viral Activities of Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Against Human Respiratory Viruses. Front. Cell Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.850744"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1016\/j.jid.2017.03.041","article-title":"STING Is Involved in Antiviral Immune Response against VZV Infection via the Induction of Type I and III IFN Pathways","volume":"137","author":"Kim","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Lee, J.H., Oh, S.J., Yun, J., and Shin, O.S. (2021). Nonstructural Protein NS1 of Influenza Virus Disrupts Mitochondrial Dynamics and Enhances Mitophagy via ULK1 and BNIP3. Viruses, 13.","DOI":"10.3390\/v13091845"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"eabi9007","DOI":"10.1126\/sciimmunol.abi9007","article-title":"Pharmacological activation of STING blocks SARS-CoV-2 infection","volume":"6","author":"Li","year":"2021","journal-title":"Sci. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1016\/j.chom.2023.08.001","article-title":"Pathogen-driven CRISPR screens identify TREX1 as a regulator of DNA self-sensing during influenza virus infection","volume":"31","author":"King","year":"2023","journal-title":"Cell Host Microbe"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"F608","DOI":"10.1152\/ajprenal.00554.2020","article-title":"The novel STING antagonist H151 ameliorates cisplatin-induced acute kidney injury and mitochondrial dysfunction","volume":"320","author":"Gong","year":"2021","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41586-018-0287-8","article-title":"Targeting STING with covalent small-molecule inhibitors","volume":"559","author":"Haag","year":"2018","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zhang, K., Wang, S., Gou, H., Zhang, J., and Li, C. (2021). Crosstalk Between Autophagy and the cGAS-STING Signaling Pathway in Type I Interferon Production. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.748485"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.molcel.2013.05.022","article-title":"Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING","volume":"51","author":"Zhang","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"eabi9002","DOI":"10.1126\/sciimmunol.abi9002","article-title":"A diamidobenzimidazole STING agonist protects against SARS-CoV-2 infection","volume":"6","author":"Humphries","year":"2021","journal-title":"Sci. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1039\/D0CC06959K","article-title":"A novel STING agonist for cancer immunotherapy and a SARS-CoV-2 vaccine adjuvant","volume":"57","author":"Wu","year":"2021","journal-title":"Chem. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"E2058","DOI":"10.1073\/pnas.1716937115","article-title":"STING-dependent translation inhibition restricts RNA virus replication","volume":"115","author":"Franz","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.virs.2023.06.006","article-title":"STING strengthens host anti-hantaviral immunity through an interferon-independent pathway","volume":"38","author":"Wang","year":"2023","journal-title":"Virol. Sin."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Amurri, L., Horvat, B., and Iampietro, M. (2023). Interplay between RNA viruses and cGAS\/STING axis in innate immunity. Front. Cell Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1172739"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/6\/855\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:49:23Z","timestamp":1760107763000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/6\/855"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,27]]},"references-count":22,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["v16060855"],"URL":"https:\/\/doi.org\/10.3390\/v16060855","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,27]]}}}