Integrated Omics Analysis of Pathogenic Host Responses during Pandemic H1N1 Influenza Virus Infection: The Crucial Role of Lipid Metabolism

Abstract

SUMMARY Pandemic influenza viruses modulate pro-inflammatory responses that can lead to immunopathogenesis. We present an extensive and systematic profiling of lipids, metabolites and proteins in respiratory compartments of ferrets infected with either 1918 or 2009 human pandemic H1N1 influenza viruses. Integrative analysis of high-throughput omics data with virologic and histopathologic data uncovered relationships between host responses and phenotypic outcomes of viral infection. Pro-inflammatory lipid precursors in the trachea following 1918 infection correlated with severe tracheal lesions. Using an algorithm to infer cell quantity changes from gene expression data, we found enrichment of distinct T cell subpopulations in the trachea. There was also a predicted increase in inflammatory monocytes in the lung of 1918 virus-infected animals that was sustained throughout infection. This study presents a unique resource to the influenza research community and demonstrates the utility of an integrative systems approach for characterization of lipid metabolism alterations underlying respiratory responses to viruses.

Metabolic alterations in multiple sclerosis and the impact of vitamin D supplementation

“…WGCNA is a systems biology method that was originally developed to characterize correlation patterns among genes from microarray studies. It has been applied in other settings, such as metabolomics, cancer, and analysis of brain imaging data (39)(40)(41)(42). As an analytic technique, its primary goal is to find clusters (modules) of interconnected nodes (e.g., metabolites in this case), and it allows summary measures of the clusters to be used in subsequent analysis.…”

The MPLEx Protocol for Multi-omic Analyses of Soil Samples

“…While the MPLEx protocol has been well-established for general extraction of lipids and metabolites 12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,34, its comparison to common soil protein extraction methods for microbial analyses, such as soil protein extraction kits (see Table of Materials ) and SDS (sodium dodecyl sulfate) extractions 35 , is further evaluated here. To assess these techniques, Kansas native prairie soil proteins were extracted with each approach and analyzed directly with reversed-phase LC-MS/MS using a UPLC system coupled with a hybrid quadrupole/Orbitrap mass spectrometer.…”

“…This method was originally developed for total lipid extractions 9,11 and more recently was amended for the simultaneous extraction of metabolites, proteins, and lipids from a single sample 12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30, enabling less sample quantity and experimental variability 10 . In the MPLEx protocol, chloroform is not miscible with water, which provides the basis for the triphasic chemical separation of sample constituents into distinct fractions.…”

Nanomaterial Effects on Viral Infection

“…Furthermore, changes in biosynthesis of these perturbed lipid profiles correlated with the expression of related lipid biosynthesis genes. Specific to influenza, exposure of ferrets to both historic and contemporary strains of pandemic influenza A virus revealed relationships between altered lipid metabolism and inflammation (Tisoncik-Go et al 2016). For example, the sphingomyelin module (group of species with similar co-expression relationships) was positively correlated with innate immune and lipid metabolism gene modules, as well as virus titer and levels of viral mRNA (Tisoncik-Go et al 2016).…”