tetano
Editor, Senior Moderator
Mol Ther. 2017 Jul 8. pii: S1525-0016(17)30317-9. doi: 10.1016/j.ymthe.2017.07.003. [Epub ahead of print]
[h=1]RIG-I Activation Protects and Rescues from Lethal Influenza Virus Infection and Bacterial Superinfection.[/h] Coch C[SUP]1[/SUP], St?mpel JP[SUP]2[/SUP], Lilien-Waldau V[SUP]2[/SUP], Wohlleber D[SUP]3[/SUP], K?mmerer BM[SUP]4[/SUP], Bekeredjian-Ding I[SUP]5[/SUP], Kochs G[SUP]6[/SUP], Garbi N[SUP]7[/SUP], Herberhold S[SUP]8[/SUP], Schuberth-Wagner C[SUP]2[/SUP], Ludwig J[SUP]2[/SUP], Barchet W[SUP]2[/SUP], Schlee M[SUP]2[/SUP], Hoerauf A[SUP]9[/SUP], Bootz F[SUP]8[/SUP], Staeheli P[SUP]6[/SUP], Hartmann G[SUP]2[/SUP], Hartmann E[SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] 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
[h=1]RIG-I Activation Protects and Rescues from Lethal Influenza Virus Infection and Bacterial Superinfection.[/h] Coch C[SUP]1[/SUP], St?mpel JP[SUP]2[/SUP], Lilien-Waldau V[SUP]2[/SUP], Wohlleber D[SUP]3[/SUP], K?mmerer BM[SUP]4[/SUP], Bekeredjian-Ding I[SUP]5[/SUP], Kochs G[SUP]6[/SUP], Garbi N[SUP]7[/SUP], Herberhold S[SUP]8[/SUP], Schuberth-Wagner C[SUP]2[/SUP], Ludwig J[SUP]2[/SUP], Barchet W[SUP]2[/SUP], Schlee M[SUP]2[/SUP], Hoerauf A[SUP]9[/SUP], Bootz F[SUP]8[/SUP], Staeheli P[SUP]6[/SUP], Hartmann G[SUP]2[/SUP], Hartmann E[SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] 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