Untargeted LC-MS based metabolomic profiling of iPAMs to investigate lipid metabolic pathways alternations induced by different Pseudorabies virus strains.

Owing to viral recombination, interspecies transmission, and evolution, variant pseudorabies virus (PRV) strains exhibit different biological characteristics and pathogenicity. To improve the understanding of common and specific metabolic changes that occur upon infection by different PRV strains, we herein describe the comprehensive analysis of metabolites of PRV vaccine strain (Bartha K61), classical strain (EA) and variant strain (HNX) infection in immortalized porcine alveolar macrophage cells. Compared with uninfected cells, cells infected with Bartha K61, EA and HNX had 246, 225, and 272 differing metabolites, respectively. In the three types of PRV-strain-infected cells, lipids and lipid-like molecules accounted for over 50 % of the altered metabolites. As these viruses are enveloped, viral replication, assembly and release occur on cellular membranes primed through the manipulation of the host metabolism. We analyzed the potential relationship between virus replication and the virus-mediated host metabolism. Our study resulted in the first reconstruction of the major lipid metabolic pathways involved in PRV infection, including those of glycerophospholipids, sphingolipids, glycerolipids, and fatty acyls. In addition, the metabolic perturbations caused by different PRV strain infections are consistent across many species, however, our results also revealed many specific metabolic alterations during HNX infection, such as the enrichment of phosphatidylinositol and 15R-PGE2 methyl ester 15-acetate, and the diminishment of phosphatidylethanolamine, phosphatidic acid, and ceramides. These strain-specific altered metabolites may be linked to the unique biological characteristics and pathogenicity of the HNX strain.