2. Academic Validation
  3. Lipid metabolism is a novel and practical source of potential targets for antiviral discovery against porcine parvovirus

Lipid metabolism is a novel and practical source of potential targets for antiviral discovery against porcine parvovirus

  • Vet Microbiol. 2021 Oct:261:109177. doi: 10.1016/j.vetmic.2021.109177.
Zhanzhong Zhao 1,  Jing Li 1,  Xiaohui Feng 1,  Xiangfang Tang 1,  Xiaoyu Guo 1,  Qingshi Meng 1,  Zhenghua Rao 1,  Xinghui Zhao 2,  Li Feng 3,  Hongfu Zhang 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Animal Nutrition, Beijing Institute of Animal Husbandry and Veterinary Medicine, Chinese Academy of Agricultural Sciences, Beijing, PR China.
  • 2 Department of Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA. Electronic address: [email protected].
  • 3 State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PR China. Electronic address: [email protected].
  • 4 State Key Laboratory of Animal Nutrition, Beijing Institute of Animal Husbandry and Veterinary Medicine, Chinese Academy of Agricultural Sciences, Beijing, PR China. Electronic address: [email protected].
PMID: 34391196 DOI: 10.1016/j.vetmic.2021.109177
Abstract

How parvovirus manipulates host lipid metabolism to facilitate its propagation, pathogenicity and consequences for disease, is poorly characterized. Here, we addressed this question using porcine parvovirus (PPV) to understand the complex interactions of parvovirus with lipid metabolism networks contributing to the identification of novel and practical Antiviral candidates. PPV significantly alters host lipid composition, characteristic of subclasses of Phospholipids and sphingolipids, and induces lipid droplets (LDs) formation via regulating calcium-independent PLA2β (iPLA2β), Phospholipase Cγ2 (PLCγ2), diacylglycerol kinase α (DKGα), phosphoinositide 3-kinase (PI3K), lysophosphatidic acid Acyltransferase θ (LPAATθ), and sphingosine kinases (SphK1 and SphK2). PPV utilizes and exploits these Enzymes as well as their metabolites and host factors including MAPKs (p38 and ERK1/2), protein kinase C (PKC) and CA2+ to induce S phase arrest, Apoptosis and incomplete Autophagy, all benefit to PPV propagation. PPV also suppresses prostaglandin E2 (PGE2) synthesis via downregulating cyclooxygenase-1 (COX-1), indicating PPV hijacks COX-1-PGE2 axis to evade immune surveillance. Our data support a model where PPV to establishes an optimal environment for its propagation and pathogenicity via co-opting host lipid metabolism, being positioned as a source of potential targets.

Keywords

Cellular microenvironment; Lipid metabolism; Porcine parvovirus; Potential targets; Propagation.

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