5'PPP-RNA induced RIG-I activation inhibits drug-resistant avian H5N1 as well as 1918 and 2009 pandemic influenza virus replication.
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.
Ranjan
Priya
P
Influenza Division, NCIRD, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Jayashankar
Lakshmi
L
Deyde
Varough
V
Zeng
Hui
H
Davis
William G
WG
Pearce
Melissa B
MB
Bowzard
John B
JB
Hoelscher
Mary A
MA
Jeisy-Scott
Victoria
V
Wiens
Mayim E
ME
Gangappa
Shivaprakash
S
Gubareva
Larisa
L
García-Sastre
Adolfo
A
Katz
Jacqueline M
JM
Tumpey
Terrence M
TM
Fujita
Takashi
T
Sambhara
Suryaprakash
S
D000818:Animals; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D004196:Disease Outbreaks; D024882:Drug Resistance, Viral; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D007251:Influenza, Human / Q000453:epidemiology / Q000235:genetics / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012367:RNA, Viral / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D011971:Receptors, Immunologic; D014779:Virus Replication
C551867:5'PPP-RNA; D012367:RNA, Viral; D011971:Receptors, Immunologic; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases