Lipidomics of Influenza Virus: Implications of Host Cell Choline-and Sphingolipid Metabolism

Abstract

We harnessed a comprehensive lipidomics approach using mass spectrometry to elucidate the role of lipids during influenza virus replication. The levels of several host lipids, especially choline containing species, were altered in infected human lung epithelial cells. Specifically, saturated sphingomyelin (SM) and ether linked phosphatidylcholine species (ePC) were elevated with a concomitant decrease in ester linked phosphatidylcholine species (aPC). Purified virus particles exhibited a similar trend unique to influenza virus and interfering with SM and ether lipid biosynthesis impaired its production. We identified influenza virus non-structural protein 1 (NS1) as a determinant for host cell lipid metabolism underlined by distinct lipid compositions of two related influenza virus strains differing in a point mutation in NS1. We propose a model whereby influenza virus redirects glycolytic flux into the biosynthesis of ether linked- and sphingolipids to facilitate virion replication and morphogenesis in the exocytotic pathway which correlates with virus pathogenicity.