Activation of the innate immune system provides broad-spectrum protection against influenza A viruses with pandemic potential in mice.
The efficacy of a stabilized chemical analog of double-stranded ribonucleic acid (RNA), PIKA, as prophylaxis against infection with 5 different influenza A virus subtypes, including the 2009 swine-origin pandemic H1N1 virus, was evaluated in mice. Intranasal treatment with PIKA resulted in a significant reduction of viral replication in the respiratory tract. The inhibitory effect was mediated by rapid infiltration of immune cells into the lungs, and production of inflammatory cytokines. While TLR3 is important for the optimal production of these inflammatory cytokines, inhibition of viral replication was still observed in TLR3(-/-) mice. In addition, a significant synergistic effect in inhibiting H5N1 virus replication was observed when PIKA was coadministered with oseltamivir. The broad-spectrum protection provided by PIKA makes it an attractive option for prophylaxis from infection with influenza A viruses.
Lau
Yuk-Fai
YF
Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
Tang
Lay-Hoon
LH
Ooi
Eng-Eong
EE
Subbarao
Kanta
K
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D054884:Host-Pathogen Interactions / Q000276:immunology; D007113:Immunity, Innate; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D009980:Influenza A virus / Q000276:immunology* / Q000472:pathogenicity* / Q000502:physiology; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D053139:Oseltamivir / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000494:pharmacology; D051196:Toll-Like Receptor 3 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D016207:Cytokines; D012330:RNA, Double-Stranded; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D053139:Oseltamivir