Induction of Interferon-Stimulated Genes Correlates with Reduced Growth of Influenza A Virus in Lungs after RIG-I Agonist Treatment of Ferrets

LSU Schwab; SL Londrigan; AG Brooks; AC Hurt; A Sahu; YM Deng; J Moselen; C Coch; T Zillinger; G Hartmann; PC Reading

Journal article

Induction of Interferon-Stimulated Genes Correlates with Reduced Growth of Influenza A Virus in Lungs after RIG-I Agonist Treatment of Ferrets

LSU Schwab, SL Londrigan, AG Brooks, AC Hurt, A Sahu, YM Deng, J Moselen, C Coch, T Zillinger, G Hartmann, PC Reading

Journal of Virology | AMER SOC MICROBIOLOGY | Published : 2022

DOI: 10.1128/jvi.00559-22

Abstract

Intracellular RIG-I receptors represent key innate sensors of RNA virus infection, and RIG-I activation results in the induction of hundreds of host effector genes, including interferon-stimulated genes (ISGs). Synthetic RNA agonists targeting RIG-I have shown promise as antivirals against a broad spectrum of viruses, including influenza A virus (IAV), in both in vitro and mouse models of infection. Herein, we demonstrate that treatment of a ferret airway epithelial (FRL) cell line with a RIG-I agonist rapidly and potently induced expression of a broad range of ISGs and resulted in potent inhibition of growth of different IAV strains. In ferrets, a single intravenous injection of RIG-I agoni..

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University of Melbourne Researchers

Lara Schwab Author

Sarah Londrigan Author

Andrew Brooks Author

Patrick Reading Author

Related Projects (1)

IDENTIFICATION OF HOST RESTRICTION FACTORS THAT BLOCK RESPIRATORY VIRUS INFECTION

Following inhalation, respiratory viruses can infect and grow in airway epithelial cells. Although immune cells such as macrophages are also..

Grants

Awarded by Deutsches Zentrum für Infektionsforschung

Funding Acknowledgements

FRL cells prepared by Tuck-Weng Kok (University of Adelaide) were obtained from Commonwealth Science and Industrial Research Organisation, Health & Biosecurity, Australian Centre for Disease Preparedness, Victoria, Australia. This work was supported by project grant APP1143154 from the National Health and Medical Research Council (NHMRC) of Australia. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health. Additionally, this work was supported by the German Center for Infectious Diseases (DZIF) TTU 07.834_00 to G.H., by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Project ID 369799452 -TRR237 to G.H., and under Germany's Excellence Strategy-EXC2151-390873048, of which G.H. is a member. We thank the Melbourne Flow Cytometry Core Platformfor assistance with flow cytometric analysis.