hydroxyoctadecadienoic-acid and Influenza--Human

Influenza is a leading cause of morbidity and mortality worldwide, with vaccines and antiviral drugs having limited efficacy thus far. Two recent studies in Cell apply lipidomics approaches to identify bioactive lipid mediators influencing host inflammation, viral replication, and disease progression.

Topics: Active Transport, Cell Nucleus; Animals; Docosahexaenoic Acids; Eicosanoids; Fatty Acids, Unsaturated; Humans; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza A Virus, H5N1 Subtype; Influenza, Human; Lipids; Orthomyxoviridae Infections; Virus Replication

Bioactive lipid mediators play a crucial role in the induction and resolution of inflammation. To elucidate their involvement during influenza infection, liquid chromatography/mass spectrometry lipidomic profiling of 141 lipid species was performed on a mouse influenza model using two viruses of significantly different pathogenicity. Infection by the low-pathogenicity strain X31/H3N2 induced a proinflammatory response followed by a distinct anti-inflammatory response; infection by the high-pathogenicity strain PR8/H1N1 resulted in overlapping pro- and anti-inflammatory states. Integration of the large-scale lipid measurements with targeted gene expression data demonstrated that 5-lipoxygenase metabolites correlated with the pathogenic phase of the infection, whereas 12/15-lipoxygenase metabolites were associated with the resolution phase. Hydroxylated linoleic acid, specifically the ratio of 13- to 9-hydroxyoctadecadienoic acid, was identified as a potential biomarker for immune status during an active infection. Importantly, some of the findings from the animal model were recapitulated in studies of human nasopharyngeal lavages obtained during the 2009-2011 influenza seasons.

Topics: Animals; Arachidonate 5-Lipoxygenase; Cytokines; Disease Models, Animal; Eicosanoids; Fatty Acids, Unsaturated; Humans; Inflammation Mediators; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza, Human; Lipids; Metabolic Networks and Pathways; Mice; Nasal Lavage Fluid; Orthomyxoviridae Infections; Transcriptome