ImmunoSensation - the immune sensory system

J Infect Dis . 2022 Jul 21

RIG-I activation inhibits human respiratory syncytial virus replication in mammalian cells and in mouse and ferret models of infection

Lara S U Schwab, Rubaiyea Farrukee, Jean François Eléouët, Marie Anne Rameix-Welti, Sarah L Londrigan, Andrew G Brooks, Aeron C Hurt, Christoph Coch, Thomas Zillinger, Gunther Hartmann, Patrick C Reading

Infections caused by human respiratory syncytial virus (RSV) are associated with substantial morbidity and mortality. Treatment options are limited and there is urgent need for the development of efficient antivirals. Pattern recognition receptors such as the cytoplasmic helicase retinoic-acid-inducible gene (RIG)-I can be activated by viral nucleic acids, leading to activation of interferon-stimulated genes and generation of an 'antiviral state'. Here we activate RIG-I with synthetic RNA agonists (3pRNA) to induce resistance to RSV infection in vitro and in vivo. In vitro, pre-treatment of human, mouse and ferret airway cell lines with RIG-I agonist prior to RSV exposure inhibited virus infection and replication. Moreover, a single intravenous injection of 3pRNA one day prior to RSV infection resulted in potent inhibition of virus replication in the lungs of mice and ferrets, but not in nasal tissues. These studies provide evidence that RIG-I agonists represent a promising antiviral drug for RSV prophylaxis.

PMID: 35861054