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Mol Ther. 2017 Jul 8. pii: S1525-0016(17)30317-9. doi: 10.1016/j.ymthe.2017.07.003. [Epub ahead of print]
RIG-I Activation Protects and Rescues from Lethal Influenza Virus Infection and Bacterial Superinfection.
Coch C1, St?mpel JP2, Lilien-Waldau V2, Wohlleber D3, K?mmerer BM4, Bekeredjian-Ding I5, Kochs G6, Garbi N7, Herberhold S8, Schuberth-Wagner C2, Ludwig J2, Barchet W2, Schlee M2, Hoerauf A9, Bootz F8, Staeheli P6, Hartmann G2, Hartmann E8.
Author information
Abstract
Influenza A virus infection causes substantial morbidity and mortality in seasonal epidemic outbreaks, and more efficient treatments are urgently needed. Innate immune sensing of viral nucleic acids stimulates antiviral immunity, including cell-autonomous antiviral defense mechanisms that restrict viral replication. RNA oligonucleotide ligands that potently activate the cytoplasmic helicase retinoic-acid-inducible gene I (RIG-I) are promising candidates for the development of new antiviral therapies. Here, we demonstrate in an Mx1-expressing mouse model of influenza A virus infection that a single intravenous injection of low-dose RIG-I ligand 5'-triphosphate RNA (3pRNA) completely protected mice from a lethal challenge with influenza A virus for at least 7 days. Furthermore, systemic administration of 3pRNA rescued mice with pre-established fulminant influenza infection and prevented the fatal effects of a streptococcal superinfection. Type I interferon, but not interferon-λ, was required for the therapeutic effect. Our results suggest that the use of RIG-I activating oligonucleotide ligands has the clinical potential to confine influenza epidemics when a strain-specific vaccine is not yet available and to reduce lethality of influenza in severely infected patients.
Copyright ? 2017. Published by Elsevier Inc.
KEYWORDS:
5? triphosphate RNA; RIG-I; antivirals; immunostimulatory oligonucleotides; immunotherapy; influenza virus; innate immunity; negative strand RNA virus; type I interferon; type III interferon
PMID: 28760668 DOI: 10.1016/j.ymthe.2017.07.003
RIG-I Activation Protects and Rescues from Lethal Influenza Virus Infection and Bacterial Superinfection.
Coch C1, St?mpel JP2, Lilien-Waldau V2, Wohlleber D3, K?mmerer BM4, Bekeredjian-Ding I5, Kochs G6, Garbi N7, Herberhold S8, Schuberth-Wagner C2, Ludwig J2, Barchet W2, Schlee M2, Hoerauf A9, Bootz F8, Staeheli P6, Hartmann G2, Hartmann E8.
Author information
Abstract
Influenza A virus infection causes substantial morbidity and mortality in seasonal epidemic outbreaks, and more efficient treatments are urgently needed. Innate immune sensing of viral nucleic acids stimulates antiviral immunity, including cell-autonomous antiviral defense mechanisms that restrict viral replication. RNA oligonucleotide ligands that potently activate the cytoplasmic helicase retinoic-acid-inducible gene I (RIG-I) are promising candidates for the development of new antiviral therapies. Here, we demonstrate in an Mx1-expressing mouse model of influenza A virus infection that a single intravenous injection of low-dose RIG-I ligand 5'-triphosphate RNA (3pRNA) completely protected mice from a lethal challenge with influenza A virus for at least 7 days. Furthermore, systemic administration of 3pRNA rescued mice with pre-established fulminant influenza infection and prevented the fatal effects of a streptococcal superinfection. Type I interferon, but not interferon-λ, was required for the therapeutic effect. Our results suggest that the use of RIG-I activating oligonucleotide ligands has the clinical potential to confine influenza epidemics when a strain-specific vaccine is not yet available and to reduce lethality of influenza in severely infected patients.
Copyright ? 2017. Published by Elsevier Inc.
KEYWORDS:
5? triphosphate RNA; RIG-I; antivirals; immunostimulatory oligonucleotides; immunotherapy; influenza virus; innate immunity; negative strand RNA virus; type I interferon; type III interferon
PMID: 28760668 DOI: 10.1016/j.ymthe.2017.07.003