TY - JOUR
T1 - 5'PPP-RNA induced RIG-I activation inhibits drug-resistant avian H5N1 as well as 1918 and 2009 pandemic influenza virus replication
AU - Ranjan, Priya
AU - Jayashankar, Lakshmi
AU - Deyde, Varough
AU - Zeng, Hui
AU - Davis, William G.
AU - Pearce, Melissa B.
AU - Bowzard, John B.
AU - Hoelscher, Mary A.
AU - Jeisy-Scott, Victoria
AU - Wiens, Mayim E.
AU - Gangappa, Shivaprakash
AU - Gubareva, Larisa
AU - García-Sastre, Adolfo
AU - Katz, Jacqueline M.
AU - Tumpey, Terrence M.
AU - Fujita, Takashi
AU - Sambhara, Suryaprakash
N1 - Funding Information:
We thank Alexander Klimov and Nancy Cox for their advice and critical reading of this manuscript. These studies are funded by a grant awarded to SS by National Vaccine Program Office, and by NIAID grants RO1 AI46954, U19 AI62623, P01 AI058113, U19 AI83025, and CRIP (Center for Research on Influenza Pathogenesis, NIAID contract number HHSN266200700010C to AG-S. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the funding agency or Centers for Disease Control and Prevention.
PY - 2010
Y1 - 2010
N2 - Background. Emergence of drug-resistant strains of influenza viruses, including avian H5N1 with pandemic potential, 1918 and 2009 A/H1N1 pandemic viruses to currently used antiviral agents, neuraminidase inhibitors and M2 Ion channel blockers, underscores the importance of developing novel antiviral strategies. Activation of innate immune pathogen sensor Retinoic Acid Inducible Gene-I (RIG-I) has recently been shown to induce antiviral state. Results. In the present investigation, using real time RT-PCR, immunofluorescence, immunoblot, and plaque assay we show that 5'PPP-containing single stranded RNA (5'PPP-RNA), a ligand for the intracytoplasmic RNA sensor, RIG-I can be used as a prophylactic agent against known drug-resistant avian H5N1 and pandemic influenza viruses. 5'PPP-RNA treatment of human lung epithelial cells inhibited replication of drug-resistant avian H5N1 as well as 1918 and 2009 pandemic influenza viruses in a RIG-I and type 1 interferon dependant manner. Additionally, 5'PPP-RNA treatment also inhibited 2009 H1N1 viral replication in vivo in mice. Conclusions. Our findings suggest that 5'PPP-RNA mediated activation of RIG-I can suppress replication of influenza viruses irrespective of their genetic make-up, pathogenicity, and drug-sensitivity status.
AB - Background. Emergence of drug-resistant strains of influenza viruses, including avian H5N1 with pandemic potential, 1918 and 2009 A/H1N1 pandemic viruses to currently used antiviral agents, neuraminidase inhibitors and M2 Ion channel blockers, underscores the importance of developing novel antiviral strategies. Activation of innate immune pathogen sensor Retinoic Acid Inducible Gene-I (RIG-I) has recently been shown to induce antiviral state. Results. In the present investigation, using real time RT-PCR, immunofluorescence, immunoblot, and plaque assay we show that 5'PPP-containing single stranded RNA (5'PPP-RNA), a ligand for the intracytoplasmic RNA sensor, RIG-I can be used as a prophylactic agent against known drug-resistant avian H5N1 and pandemic influenza viruses. 5'PPP-RNA treatment of human lung epithelial cells inhibited replication of drug-resistant avian H5N1 as well as 1918 and 2009 pandemic influenza viruses in a RIG-I and type 1 interferon dependant manner. Additionally, 5'PPP-RNA treatment also inhibited 2009 H1N1 viral replication in vivo in mice. Conclusions. Our findings suggest that 5'PPP-RNA mediated activation of RIG-I can suppress replication of influenza viruses irrespective of their genetic make-up, pathogenicity, and drug-sensitivity status.
UR - http://www.scopus.com/inward/record.url?scp=77952458811&partnerID=8YFLogxK
U2 - 10.1186/1743-422X-7-102
DO - 10.1186/1743-422X-7-102
M3 - Article
C2 - 20492658
AN - SCOPUS:77952458811
SN - 1743-422X
VL - 7
JO - Virology Journal
JF - Virology Journal
M1 - 102
ER -