Innate immune pathway modulator screen identifies STING pathway activation as a strategy to inhibit multiple families of arbo and respiratory viruses
| Author(s) | Garcia, Gustavo Jr. | |
| Author(s) | Irudayam, Joseph Ignatius | |
| Author(s) | Jeyachandran, Arjit Vijey | |
| Author(s) | Dubey, Swati | |
| Author(s) | Chang, Christina | |
| Author(s) | Castillo Cario, Sebastian | |
| Author(s) | Price, Nate | |
| Author(s) | Arumugam, Sathya | |
| Author(s) | Marquez, Angelica L. | |
| Author(s) | Shah, Aayushi | |
| Author(s) | Fanaei, Amir | |
| Author(s) | Chakravarty, Nikhil | |
| Author(s) | Joshi, Shantanu | |
| Author(s) | Sinha, Sanjeev | |
| Author(s) | French, Samuel W. | |
| Author(s) | Parcells, Mark S. | |
| Author(s) | Ramaiah, Arunachalam | |
| Author(s) | Arumugaswami, Vaithilingaraja | |
| Date Accessioned | 2023-07-19T19:58:30Z | |
| Date Available | 2023-07-19T19:58:30Z | |
| Publication Date | 2023-05-16 | |
| Description | This article was originally published in Cell Reports Medicine. The version of record is available at: https://doi.org/10.1016/j.xcrm.2023.101024. © 2023 The Authors. | |
| Abstract | Highlights: • Screen identifies innate immune agonists blocking multiple families of RNA viruses • Dectin-1 and cGAS-STING pathway agonists exhibit broader antiviral activity • STING activator cAIMP blocks ZIKV, WNV, CHIKV, EV-D68, and SARS-CoV-2 infections • cAIMP provides protection against CHIKV-mediated chronic arthritis in mouse model Summary: RNA viruses continue to remain a threat for potential pandemics due to their rapid evolution. Potentiating host antiviral pathways to prevent or limit viral infections is a promising strategy. Thus, by testing a library of innate immune agonists targeting pathogen recognition receptors, we observe that Toll-like receptor 3 (TLR3), stimulator of interferon genes (STING), TLR8, and Dectin-1 ligands inhibit arboviruses, Chikungunya virus (CHIKV), West Nile virus, and Zika virus to varying degrees. STING agonists (cAIMP, diABZI, and 2′,3′-cGAMP) and Dectin-1 agonist scleroglucan demonstrate the most potent, broad-spectrum antiviral function. Furthermore, STING agonists inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enterovirus-D68 (EV-D68) infection in cardiomyocytes. Transcriptome analysis reveals that cAIMP treatment rescue cells from CHIKV-induced dysregulation of cell repair, immune, and metabolic pathways. In addition, cAIMP provides protection against CHIKV in a chronic CHIKV-arthritis mouse model. Our study describes innate immune signaling circuits crucial for RNA virus replication and identifies broad-spectrum antivirals effective against multiple families of pandemic potential RNA viruses. Graphical abstract available at: https://doi.org/10.1016/j.xcrm.2023.101024 | |
| Sponsor | We are grateful to Barbara Dillon, UCLA High Containment Program Director, for BSL3 work. We thank Yijie Wang from the UCLA Cardiomyocyte Core for providing hPSC-CMs. This study is partly supported by National Institutes of Health awards 1R01EY032149-01, 5R01AI163216-02, and 1R01DK132735-01 to V.A. The viruses used in this study were obtained through BEI Resources, NIAID, NIH. | |
| Citation | Garcia, Gustavo, Joseph Ignatius Irudayam, Arjit Vijey Jeyachandran, Swati Dubey, Christina Chang, Sebastian Castillo Cario, Nate Price, et al. “Innate Immune Pathway Modulator Screen Identifies STING Pathway Activation as a Strategy to Inhibit Multiple Families of Arbo and Respiratory Viruses.” Cell Reports Medicine 4, no. 5 (May 16, 2023): 101024. https://doi.org/10.1016/j.xcrm.2023.101024. | |
| ISSN | 2666-3791 | |
| URL | https://udspace.udel.edu/handle/19716/33025 | |
| Language | en_US | |
| Publisher | Cell Reports Medicine | |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| Title | Innate immune pathway modulator screen identifies STING pathway activation as a strategy to inhibit multiple families of arbo and respiratory viruses | |
| Type | Article |
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