tetano
Editor, Senior Moderator
Mol Ther Nucleic Acids. 2020 Mar 6;19:1413-1422. doi: 10.1016/j.omtn.2020.01.025. Epub 2020 Jan 31. [h=1]A Dual-Functioning 5'-PPP-NS1shRNA that Activates a RIG-I Antiviral Pathway and Suppresses Influenza NS1.[/h]
Singh N[SUP]1[/SUP], Ranjan P[SUP]1[/SUP], Cao W[SUP]1[/SUP], Patel J[SUP]1[/SUP], Gangappa S[SUP]1[/SUP], Davidson BA[SUP]2[/SUP], Sullivan JM[SUP]3[/SUP], Prasad PN[SUP]4[/SUP], Knight PR[SUP]5[/SUP], Sambhara S[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Retinoic acid-inducible gene-I (RIG-I) is a cytosolic pathogen sensor that is crucial against a number of viral infections. Many viruses have evolved to inhibit pathogen sensors to suppress host innate immune responses. In the case of influenza, nonstructural protein 1 (NS1) suppresses RIG-I function, leading to viral replication, morbidity, and mortality. We show that silencing NS1 with in-vitro-transcribed 5'-triphosphate containing NS1 short hairpin RNA (shRNA) (5'-PPP-NS1shRNA), designed using the conserved region of a number of influenza viruses, not only prevented NS1 expression but also induced RIG-I activation and type I interferon (IFN) expression, resulting in an antiviral state leading to inhibition of influenza virus replication in vitro. In addition, administration of 5'-PPP-NS1shRNA in prophylactic and therapeutic settings resulted in significant inhibition of viral replication following viral challenge in vivo in mice with corresponding increases of RIG-I, IFN-β, and IFN-λ, as well as a decrease in NS1 expression.
Published by Elsevier Inc.
[h=4]KEYWORDS:[/h] 5'PPP-RNA; Influenza; Interferon; NS1; RIG-I; antiviral; shRNA
PMID: 32160710 DOI: 10.1016/j.omtn.2020.01.025
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Singh N[SUP]1[/SUP], Ranjan P[SUP]1[/SUP], Cao W[SUP]1[/SUP], Patel J[SUP]1[/SUP], Gangappa S[SUP]1[/SUP], Davidson BA[SUP]2[/SUP], Sullivan JM[SUP]3[/SUP], Prasad PN[SUP]4[/SUP], Knight PR[SUP]5[/SUP], Sambhara S[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Retinoic acid-inducible gene-I (RIG-I) is a cytosolic pathogen sensor that is crucial against a number of viral infections. Many viruses have evolved to inhibit pathogen sensors to suppress host innate immune responses. In the case of influenza, nonstructural protein 1 (NS1) suppresses RIG-I function, leading to viral replication, morbidity, and mortality. We show that silencing NS1 with in-vitro-transcribed 5'-triphosphate containing NS1 short hairpin RNA (shRNA) (5'-PPP-NS1shRNA), designed using the conserved region of a number of influenza viruses, not only prevented NS1 expression but also induced RIG-I activation and type I interferon (IFN) expression, resulting in an antiviral state leading to inhibition of influenza virus replication in vitro. In addition, administration of 5'-PPP-NS1shRNA in prophylactic and therapeutic settings resulted in significant inhibition of viral replication following viral challenge in vivo in mice with corresponding increases of RIG-I, IFN-β, and IFN-λ, as well as a decrease in NS1 expression.
Published by Elsevier Inc.
[h=4]KEYWORDS:[/h] 5'PPP-RNA; Influenza; Interferon; NS1; RIG-I; antiviral; shRNA
PMID: 32160710 DOI: 10.1016/j.omtn.2020.01.025
Free full text