1. 5'PPP-RNA induced RIG-I activation inhibits drug-resistant avian H5N1 as well as 1918 and 2009 pandemic influenza virus replication
- Author
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Mary Hoelscher, Hui Zeng, Jacqueline M. Katz, Melissa B. Pearce, Shivaprakash Gangappa, Varough M. Deyde, Mayim E Wiens, John B. Bowzard, Suryaprakash Sambhara, Larisa V. Gubareva, Terrence M. Tumpey, Priya Ranjan, William G. Davis, Takashi Fujita, Victoria Jeisy-Scott, Adolfo García-Sastre, and Lakshmi Jayashankar
- Subjects
Oseltamivir ,viruses ,Biology ,Virus Replication ,medicine.disease_cause ,Cell Line ,Disease Outbreaks ,Microbiology ,lcsh:Infectious and parasitic diseases ,DEAD-box RNA Helicases ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Influenza A Virus, H1N1 Subtype ,0302 clinical medicine ,Virology ,Drug Resistance, Viral ,Influenza, Human ,medicine ,Animals ,Humans ,lcsh:RC109-216 ,030212 general & internal medicine ,Receptors, Immunologic ,Pathogen ,030304 developmental biology ,Virus quantification ,Mice, Inbred BALB C ,0303 health sciences ,Influenza A Virus, H5N1 Subtype ,RIG-I ,Research ,RNA ,virus diseases ,Influenza A virus subtype H5N1 ,3. Good health ,Infectious Diseases ,Viral replication ,chemistry ,biology.protein ,DEAD Box Protein 58 ,RNA, Viral ,Neuraminidase - Abstract
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.
- Published
- 2010