Multi-omics dissection of metabolic hijacking: Infectious bronchitis virus orchestrates lipid-centric replication through PPAR-TGF-β crosstalk.
IBV manipulates host lipid metabolism to support its replication, highlighting potential metabolic targets for antiviral strategies.
Where it sits
this study against the rest of the ace-031 (acvr2b-fc) corpusSummary and findings
The study investigates the metabolic reprogramming induced by avian infectious bronchitis virus (IBV) in chickens, focusing on glucose and lipid metabolism. It employs multi-omics approaches to reveal how IBV redirects metabolic pathways to support its replication. The research identifies potential metabolic targets for antiviral intervention.
Abstract
Avian infectious bronchitis virus (IBV) belongs to the genus <i>Gammacoronavirus</i> (family <i>Coronaviridae</i>), 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 <i>de novo</i> 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 A<sub>2</sub> (PLA<sub>2</sub>)-mediated lysophospholipids (Lyso-PLs) and eicosanoids generation (e.g. 7.09-fold increase in prostaglandin E<sub>2</sub> (PGE<sub>2</sub>)) 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 <i>in vitro</i>. 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.
Background
The study addresses the metabolic interactions between avian infectious bronchitis virus (IBV) and its host, focusing on how the virus manipulates host metabolic pathways to facilitate its replication. Previous research has not fully elucidated the molecular mechanisms underlying this metabolic hijacking. Understanding these interactions is crucial for developing targeted antiviral strategies.
Methods
The study utilized integrated transcriptomic, metabolomic, and lipidomic profiling of oviduct tissues from specific-pathogen-free chickens infected with the IBV QXL strain. It focused on metabolic pathways, including glucose flux, lipid metabolism, and glycerophospholipid remodeling. The primary outcomes were changes in metabolic pathway activity and lipid composition.
Results
The primary finding was a 2.55-fold increase in phosphatidylserine, alongside a 7.09-fold increase in prostaglandin E2, indicating significant lipid remodeling. The study also reported a 1.74-fold increase in ACSL1 expression and significant activation of the PPAR and TGF-β signaling pathways. These changes were associated with redirected glucose flux and lipid metabolism, supporting viral replication.
Interpretation
The findings suggest that IBV exploits host metabolic pathways, particularly lipid metabolism, to enhance its replication. While the effect sizes are statistically significant, the clinical relevance remains uncertain due to the study's focus on chickens and in vitro models. This research provides insights into potential metabolic targets for antiviral therapy, although further validation in human models is necessary.
Key findings
- 2.55-fold increase in phosphatidylserine (PS(22:0/22:6))
- 7.09-fold increase in prostaglandin E2 (PGE2)
- 1.74-fold increase in ACSL1 expression
- Significant increase in p-SMAD2
- Tripartite metabolic reprogramming observed in infected chickens
Limitations
- Conducted in chickens, not humans
- Primarily mechanistic findings
- In vitro observations
- No direct clinical outcomes reported