Multi-omics dissection of metabolic hijacking: Infectious bronchitis virus orchestrates lipid-centric replication...

Area of Science:

• Virology and Host-Pathogen Interactions
• Metabolomics and Lipidomics
• Molecular Biology and Immunology

Background:

• Avian infectious bronchitis virus (IBV), a Gammacoronavirus, causes significant economic losses in poultry due to multi-systemic disease.
• The intricate molecular mechanisms governing the interplay between IBV and host metabolic networks are not well understood.
• Understanding host metabolic reprogramming is crucial for developing effective antiviral interventions.

Purpose of the Study:

• To elucidate the metabolic reprogramming induced by IBV infection in chicken oviduct tissues.
• To identify key host metabolic pathways and signaling networks co-opted by IBV.
• To explore potential host-targeted antiviral strategies based on metabolic interventions.

Main Methods:

• Integrated transcriptomic, metabolomic, and lipidomic profiling of oviduct tissues from IBV-infected specific-pathogen-free (SPF) chickens.
• Analysis of metabolic flux, gene expression, and lipid accumulation.
• In vitro validation of antiviral strategies targeting key metabolic enzymes and signaling pathways.

Main Results:

• Demonstrated tripartite metabolic reprogramming: enhanced pentose phosphate pathway (PPP) activity, prioritized de novo lipogenesis for membrane biogenesis, and altered glycerophospholipid metabolism.
• Identified IBV's exploitation of the Warburg effect and PPP activation, coupled with suppressed fatty acid oxidation, to promote lipid droplet biogenesis.
• Revealed phosphatidylserine (PS) overproduction and increased lysophospholipids (Lyso-PLs) and eicosanoids (e.g., PGE2) regulated by phospholipase A2 (PLA2), linked to PPAR and TGF-β pathway activation.

Conclusions:

• IBV infection triggers a coordinated metabolic shift, favoring nucleotide and lipid synthesis for viral propagation.
• A critical cross-talk between peroxisome proliferator-activated receptor (PPAR) and transforming growth factor-beta (TGF-β) signaling governs lipid remodeling and immunomodulation during IBV infection.
• Targeting host metabolic nodes, specifically acetyl-CoA carboxylase (ACC), glucose-6-phosphate dehydrogenase (G6PD), and the TGF-β pathway, demonstrates synergistic antiviral potential.