2. Academic Validation
  3. Neuroinvasive virus facilitates viral replication by employing lipid droplets to reduce arachidonic acid-induced ferroptosis

Neuroinvasive virus facilitates viral replication by employing lipid droplets to reduce arachidonic acid-induced ferroptosis

  • J Biol Chem. 2024 Mar 13:107168. doi: 10.1016/j.jbc.2024.107168.
Jianqing Zhao 1,  Qianruo Wang 2,  Zhenkun Liu 1,  Mai Zhang 1,  Jinquan Li 2,  Zhen F Fu 1,  Ling Zhao 3,  Ming Zhou 4
Affiliations

Affiliations

  • 1 National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China; Key Laboratory of Preventive Veterinary Medicine of Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan 430070, China.
  • 2 College of Biomedicine and Health, College of Life Science and Technology, Huazhong Agricultural University Wuhan 430070, China.
  • 3 National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China; Hubei Hongshan Laboratory, Wuhan 430070, China; Key Laboratory of Preventive Veterinary Medicine of Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan 430070, China. Electronic address: zling604@outlook.com.
  • 4 National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China; Key Laboratory of Preventive Veterinary Medicine of Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan 430070, China. Electronic address: mikchail@163.com.
PMID: 38490434 DOI: 10.1016/j.jbc.2024.107168
Abstract

Lipids have been previously implicated in the lifecycle of neuroinvasive viruses. However, the role of lipids in programmed cell death (PCD) and the relationship between PCD and lipid droplets (LDs) in neuroinvasive virus Infection remains unclear. Here, we found that the Infection of neuroinvasive virus, such as rabies virus (RABV) and encephalomyocarditis virus (EMCV) could enhance the LD formation in N2a cells, and decreasing LDs production by targeting diacylglycerol Acyltransferase (DGAT) could suppress viral replication. The lipidomics analysis revealed that arachidonic acid (AA) was significantly increased after reducing LD formation by restricting DGAT, and AA was further demonstrated to induce Ferroptosis to inhibit neuroinvasive virus replication. Moreover, lipid peroxidation and viral replication inhibition could be significantly alleviated by a Ferroptosis inhibitor, ferrostatin-1, indicating that AA affected neuroinvasive virus replication mainly through inducing Ferroptosis. Furthermore, AA was demonstrated to activate the Acyl-CoA synthetase long-chain family member 4 (ACSL4) - Lysophosphatidylcholine Acyltransferase 3 (LPCAT3) - Cytochrome P450 Oxidoreductase (POR) axis to induce Ferroptosis. Our findings highlight novel cross-talks among viral Infection, LDs and Ferroptosis for the first time, providing a potential target for Antiviral drug development.

Keywords

arachidonic acid; diacylglycerol acyltransferase; ferroptosis; lipid droplets; lipid peroxidation; neuroinvasive virus.

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