Avian infectious bronchitis virus (IBV) belongs to the genus Gammacoronavirus (family Coronaviridae), causes severe multi-system disease in chickens, inflicting major global economic losses. The molecular interplay between IBV and host metabolic networks remains poorly understood. Through integrated transcriptomic, metabolomic, and lipidomic profiling of oviduct tissues from specific-pathogen-free (SPF) chickens infected with the IBV QXL strain, we demonstrate tripartite metabolic reprogramming: (1) redirected glucose flux through the pentose phosphate pathway (PPP) to fuel nucleotide synthesis, (2) rewired lipid metabolism to prioritize de novo membrane biogenesis over fatty acid β-oxidation, and (3) orchestrated glycerophospholipid remodeling. This integrated analysis revealed a coordinated upregulation of fatty-acid biosynthesis genes and accumulation of specific glycerophospholipids and eicosanoids. Mechanistically, IBV co-opts the Warburg effect and PPP activation while uniquely suppressing fatty acid β-oxidation to channel fatty acids toward lipid droplets (LDs) biogenesis. Phosphatidylserine (PS) overproduction (e.g. 2.55-fold increase in PS(22:0/22:6)) and phospholipase A2 (PLA2)-mediated lysophospholipids (Lyso-PLs) and eicosanoids generation (e.g. 7.09-fold increase in prostaglandin E2 (PGE2)) emerged as critical regulators of membrane dynamics and inflammatory signaling. This process was centrally coordinated by the significant activation of peroxisome proliferator-activated receptor (PPAR) (e.g. 1.74-fold increase in ACSL1) and transforming growth factor-beta (TGF-β) (e.g. significant increase in p-SMAD2) signaling pathways, directly linking lipid remodeling to immunomodulation. Functionally, targeting acetyl-CoA carboxylase (ACC) or glucose-6-phosphate dehydrogenase (G6PD), alongside TGF-β pathway modulation, synergistically curtailed viral replication in vitro. Our findings delineate a critical PPAR-TGF-β cross-talk that governs lipid remodeling during infection and identify host metabolic nodes that are potentially targetable for antiviral intervention.
Yan et al. (Wed,) studied this question.