In vitro anti-influenza A activity of interferon (IFN)-λ1 combined with IFN-β or oseltamivir carboxylate

Tuesday, September 23, 2014 — Poster Session III
12:00 p.m. – 2:00 p.m.	FAES Academic Center	FDA/CBER	VIROL-4

* FARE Award Winner

Authors

• N.A. Ilyushina
• R.P. Donnelly

Abstract

Influenza viruses pose a continuous threat to humans because of their ability to cross species barriers and adapt to new hosts. The currently available influenza antivirals have a number of limitations; therefore, there is a need to identify other antiviral strategies, including novel drugs and drug combinations. We examined the effects of interferon (IFN)-β, IFN-λ1, oseltamivir carboxylate (a neuraminidase (NA) inhibitor), and combinations of these agents against two seasonal H1N1 and H3N2 influenza viruses in vitro. We observed that both isolates were equally sensitive to the antiviral activity of IFN-β and oseltamivir carboxylate in A549 and Calu-3 cells. In contrast, IFN-λ1 exhibited substantially lower protective potential against the H1N1 strain (64-1030 fold), and was ineffective against the H3N2 virus in both cell lines. Three dimensional analysis of the drug-drug interactions revealed that anti-influenza agents with different mechanisms of action (e.g., a NA inhibitor combined with IFN-λ1) exerted a significantly higher (P < 0.05) synergistic effect compared to co-treatment with drugs that target similar signaling pathway (i.e., type I IFN combined with type III IFN) in vitro. Our findings provide support for the combined use of interferon plus oseltamivir as a means to block influenza virus replication in vivo.

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