2. Academic Validation
  3. PLIN3-triggered lipophagic flux releases FFAs to facilitate CSFV propagation

PLIN3-triggered lipophagic flux releases FFAs to facilitate CSFV propagation

  • Virulence. 2026 Dec;17(1):2629674. doi: 10.1080/21505594.2026.2629674.
Bingke Li 1 2,  Linke Zou 1 2,  Chenchen Sun 1 2,  Jianan Jiang 1 2,  Shurou Li 1 2,  Jiaxin Wang 1 2,  Yintao He 1 2,  Yuwei Qin 1 2,  Sen Zeng 1 2,  Yiwan Song 1 2,  Weijun Zeng 1 2,  Lin Yi 1 2,  Shuangqi Fan 1 2,  Jinding Chen 1 2,  Keke Wu 1 2
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
  • 2 Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, Guangzhou, China.
PMID: 41656915 DOI: 10.1080/21505594.2026.2629674
Abstract

Viruses hijack host metabolic resources for replication. Previous studies have shown that classical swine fever virus (CSFV) Infection induces host lipid metabolic reprogramming.However, research into the exact regulatory mechanisms between CSFV and lipid metabolism remains limited. Lipophagy refers to the degradation of lipid droplet contents to release free fatty acids(FFAs), CSFV induces Autophagy to promote its replication, the regulatory mechanism between CSFV and lipophagy is unclear. In this study, we found that lipid droplets(LDs) initially accumulate and then decrease following CSFV Infection. Autophagy activity was negatively correlated with lipid drople levels. Subsequent experiments revealed that CSFV induces lipophagy in Hepatic stellate cells(HSCs)and upregulates perilipin3(PLIN3) expression, a LD-associated protein that facilitates viral replication. Further studies demonstrated that PLIN3 activates the AMPK signaling pathway to promote lipophagy-mediated FFAs release. This FFA increase could be blocked by Autophagy inhibitors. Notably, exogenous FFA addition reversed the shPLIN3-induced impairment of CSFV replication. Overall, this finding provides new insights into the mechanisms of virus-host lipid metabolism interactions.

Keywords

AMPK; CSFV; Lipid droplets; PLIN3(perilipin 3); lipophagy.

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