Assessment of the Antiviral Properties of Recombinant Porcine SP-D against Various Influenza A Viruses In Vitro

Marine L B Hillaire,Albert D M E Osterhaus,Stella E Van Trierum,Henk P Haagsman,Roland A Romijn,Wieger Hemrika,Ron A M Fouchier,Xavier Saelens,Guus F Rimmelzwaan,Thijs Kuiken,Debby Van Riel,Martin Van Eijk

doi:10.1371/journal.pone.0025005

Abstract

The emergence of influenza viruses resistant to existing classes of antiviral drugs raises concern and there is a need for novel antiviral agents that could be used therapeutically or prophylacticaly. Surfactant protein D (SP-D) belongs to the family of C-type lectins which are important effector molecules of the innate immune system with activity against bacteria and viruses, including influenza viruses. In the present study we evaluated the potential of recombinant porcine SP-D as an antiviral agent against influenza A viruses (IAVs) in vitro. To determine the range of antiviral activity, thirty IAVs of the subtypes H1N1, H3N2 and H5N1 that originated from birds, pigs and humans were selected and tested for their sensitivity to recombinant SP-D. Using these viruses it was shown by hemagglutination inhibition assay, that recombinant porcine SP-D was more potent than recombinant human SP-D and that especially higher order oligomeric forms of SP-D had the strongest antiviral activity. Porcine SP-D was active against a broad range of IAV strains and neutralized a variety of H1N1 and H3N2 IAVs, including 2009 pandemic H1N1 viruses. Using tissue sections of ferret and human trachea, we demonstrated that recombinant porcine SP-D prevented attachment of human seasonal H1N1 and H3N2 virus to receptors on epithelial cells of the upper respiratory tract. It was concluded that recombinant porcine SP-D holds promise as a novel antiviral agent against influenza and further development and evaluation in vivo seems warranted.

Highlights

influenza A viruses (IAVs) are a major cause of respiratory tract infections and cause excess morbidity and mortality every year
Biological activity of RpSP-D resembled that of Native pSP-D (NpSP-D) First, we investigated whether RpSP-D had similar biological activity against IAV compared to NpSP-D isolated from pig lungs
The antiviral activity of RpSP-D was assessed against a wide range of IAV strains

Summary

Introduction

IAV are a major cause of respiratory tract infections and cause excess morbidity and mortality every year. In addition to seasonal outbreaks of influenza epidemics in the winter months, novel influenza viruses are occasionally introduced into the human population and cause pandemics. The introduction of IAV of the H1N1, H2N2 and H3N2 subtypes have caused pandemics in 1918, 1957 and 1968 respectively. H1N1 viruses of swine origin caused the first pandemic of the 21st century, which started in Mexico in March 2009 [1,2]. The virus spread rapidly over all continents and caused disease especially in children and young adults [3]. Avian IAVs are occasionally transmitted from infected poultry to man. Highly pathogenic avian influenza viruses of the H5N1 subtype cause infections of humans relatively frequent and 60% of these cases have a fatal outcome [4,5]

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Results

Conclusion