Porcine enteric alphacoronavirus infection increases lipid droplet accumulation to facilitate the virus replication

Qi Gao ¹Yongzhi Feng ²Ting Gong ³Dongdong Wu ³Xiaoyu Zheng ²Yizhuo Luo ⁴Yunlong Yang ⁴Zebu Song ³Lang Gong ⁵Guihong Zhang³

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作者信息

1. Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control,College of Veterinary Medicine,South China Agricultural University,Guangzhou 510642,China;Maoming Branch,Guangdong Laboratory for Lingnan Modern Agriculture,Maoming 525000,China;Key Laboratory of Animal Vaccine Development,Ministry of Agriculture and Rural Affairs,Guangzhou 510000,China
2. Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control,College of Veterinary Medicine,South China Agricultural University,Guangzhou 510642,China;Key Laboratory of Animal Vaccine Development,Ministry of Agriculture and Rural Affairs,Guangzhou 510000,China
3. Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control,College of Veterinary Medicine,South China Agricultural University,Guangzhou 510642,China;Guangdong Laboratory for Lingnan Modern Agriculture,Guangzhou 510642,China
4. Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control,College of Veterinary Medicine,South China Agricultural University,Guangzhou 510642,China;Maoming Branch,Guangdong Laboratory for Lingnan Modern Agriculture,Maoming 525000,China
5. Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control,College of Veterinary Medicine,South China Agricultural University,Guangzhou 510642,China;Maoming Branch,Guangdong Laboratory for Lingnan Modern Agriculture,Maoming 525000,China;Guangdong Laboratory for Lingnan Modern Agriculture,Guangzhou 510642,China
折叠

Abstract

Coronaviruses are widely transmissible between humans and animals,causing diseases of varying severity.Porcine enteric alphacoronavirus(PEAV)is a newly-discovered pathogenic porcine enteric coronavirus in recent years,which causes watery diarrhea in newborn piglets.The host inflammatory responses to PEAV and its metabolic regulation mechanisms remain unclear,and no antiviral studies have been reported.Therefore,we investigated the pathogenic mechanism and antiviral drugs of PEAV.The transcriptomic analysis of PEAV-infected host cells revealed that PEAV could upregulate lipid metabolism pathways.In lipid metabolism,steady-state energy processes,which can be mediated by lipid droplets(LDs),are the main functions of organelles.LDs are also important in viral infection and inflammation.In infected cells,PEAV increased LD accumulation,upregulated NF-κB signaling,promoted the production of the inflammatory cytokines IL-1β and IL-8,and induced cell death.Inhibiting LD accumulation with a DGAT-1 inhibitor significantly inhibited PEAV replication,downregulated the NF-κB signaling pathway,reduced the production of IL-1β and IL-8,and inhibited cell death.The NF-κB signaling pathway inhibitor BAY11-7082 significantly inhibited LD accumulation and PEAV replication.Metformin hydrochloride also exerted anti-PEAV effects and significantly inhibited LD accumulation,downregulated the NF-κB signaling pathway,reduced the production of IL-1β and IL-8,and inhibited cell death.LD accumulation in the lipid metabolism pathway therefore plays an important role in the replication and pathogenesis of PEAV,and metformin hydrochloride inhibits LD accumulation and the inflammatory response to exert anti-PEAV activity and reducing pathological injury.These findings contribute new targets for developing treatments for PEAV infections.

Key words

porcine enteric alphacoronavirus/NF-κB inflammatory pathway/lipid droplet/metformin hydrochloride

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基金项目

National Natural Science Foundation of China(32102646)

Natural Science Foundation of Guangdong Province,China(2020A1515110315)

Startup Research Project of Maoming Laboratory,China(2021TDQD002)

China Agriculture Research System of MOF and MARA(cars-35)

出版年

2024

农业科学学报(英文)

中国农业科学院农业信息研究所

农业科学学报(英文)

CSTPCD

影响因子：0.576

ISSN：2095-3119

参考文献量48

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