脂质代谢和糖代谢在PRRSV感染宿主细胞中作用研究进展

doi:10.16431/j.cnki.1671-7236.2024.04.036

摘要/Abstract

摘要： 猪繁殖与呼吸综合征病毒(Porcine reproductive and respiratory syndrome virus,PRRSV)感染可引起母猪繁殖障碍、仔猪呼吸道疾病及公猪精液质量下降,给世界养猪业造成了巨大的经济损失。PRRSV不能自主复制,其生命周期的各个阶段均依赖于宿主的代谢系统。宿主细胞也可调节其代谢过程,以防止PRRSV复制和维持其正常生理功能。脂质代谢和糖代谢在PRRSV感染中均扮演了重要角色,PRRSV作为一种囊膜病毒对脂质代谢系统的依赖性较其他代谢系统更强。脂质参与了PRRSV生命周期的各个阶段,包括吸附、进入、复制、组装和释放,此外还与细胞炎症、免疫和凋亡有关。糖代谢也可干扰PRRSV的生命活动,从而促进或抑制PRRSV复制。文章综述了脂质代谢中脂肪酸、胆固醇、磷脂、脂滴和脂筏以及糖代谢中糖酵解和三羧酸循环在PRRSV感染宿主细胞中的作用,以期为阐明PRRSV的致病机制以及疫苗和抗PRRSV药物的研发提供基本理论依据。

关键词: 猪繁殖与呼吸综合征病毒(PRRSV); 宿主细胞; 脂质代谢; 糖代谢

Abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) infection is known to cause reproductive disorders in sows,respiratory disease in piglets,and reduce semen quality in boars,resulting in significant economic losses to the global pig industry.PRRSV is unable to replicate on its own and relies on the host metabolic system for all stages of its life cycle.Host cells,in turn,regulate their metabolic processes to hinder PRRSV replication and maintain their normal physiological functions.Both lipid metabolism and glucose metabolism play crucial roles in PRRSV infection.As an enveloped virus,PRRSV is particularly reliant on lipid metabolism systems.Lipids are involved in various stages of the PRRSV life cycle,including adsorption,entry,replication,assembly and release,it is also associated with cellular inflammation,immunity and apoptosis.Glucose metabolism can also interfere with PRRSV life activities,thereby promoting or inhibiting PRRSV replication.The roles of fatty acids,cholesterol,phospholipids,lipid droplets and lipid rafts in lipid metabolism are reviewed,along with the involvement of glycolysis and the tricarboxylic acid cycle in glucose metabolism in PRRSV-infected host cells,so to provide a theoretical basis for elucidating the pathogenic mechanism of PRRSV and contribute to the development of vaccines and anti-PRRSV drugs.

Key words: Porcine reproductive and respiratory syndrome virus (PRRSV); host cells; lipid metabolism; glucose metabolism

中图分类号:

S852.65⁺9.6

罗琴, 刘宝玲, 乔常宏, 陈翔宇, 刘丁语, 王晓虎, 王刚, 刘昊, 蔡汝健. 脂质代谢和糖代谢在PRRSV感染宿主细胞中作用研究进展[J]. 中国畜牧兽医, 2024, 51(4): 1686-1695.

LUO Qin, LIU Baoling, QIAO Changhong, CHEN Xiangyu, LIU Dingyu, WANG Xiaohu, WANG Gang, LIU Hao, CAI Rujian. Research Progress on the Role of Lipid Metabolism and Glucose Metabolism in PRRSV-infected Host Cells[J]. China Animal Husbandry and Veterinary Medicine, 2024, 51(4): 1686-1695.

参考文献

[1] LI P,SHEN Y,WANG T,et al.Epidemiological survey of PRRS and genetic variation analysis of the ORF5 gene in Shandong province,2020-2021[J].Frontiers in Veterinary Science,2022,9:987667.
[2] HAN J,ZHOU L,GE X,et al.Pathogenesis and control of the Chinese highly pathogenic Porcine reproductive and respiratory syndrome virus[J].Veterinary Microbiology,2017,209:30-47.
[3] ZHANG M,DU T,LONG F,et al.Platycodin D suppresses type 2 Porcine reproductive and respiratory syndrome virus in primary and established cell lines[J].Viruses,2018,10(11):657.
[4] GUO Z,CHEN X X,LI R,et al.The prevalent status and genetic diversity of Porcine reproductive and respiratory syndrome virus in China:A molecular epidemiological perspective[J].Virology Journal,2018,15:2.
[5] YAN J,PENG B,CHEN H,et al.On-site differential diagnostic detection of HP-PRRSV and C-PRRSV using EuNPs-mAb fluorescent probe-based immunoassay[J].Analytical and Bioanalytical Chemistry,2021,413:5799-5810.
[6] ZHOU Y,PU J,WU Y.The role of lipid metabolism in Influenza A virus infection[J].Pathogens,2021,10(3):303.
[7] MUNGER J,BAJAD S U,COLLER H A,et al.Dynamics of the cellular metabolome during Human cytomegalovirus infection[J]. PLoS Pathogens,2006,2(12):e132.
[8] YU Y,CLIPPINGER A J,ALWINE J C.Viral effects on metabolism:Changes in glucose and glutamine utilization during Human cytomegalovirus infection[J].Trends in Microbiology,2011,19(7):360-367.
[9] OSUNA-RAMOS J F,REYES-RUIZ J M,DEL A R.The role of host cholesterol during Flavivirus infection[J]. Frontiers in Cellular and Infection Microbiology,2018,8:388.
[10] THAKER S K,CHAPA T,GARCIA G J,et al.Differential metabolic reprogramming by Zika virus promotes cell death in human versus mosquito cells[J].Cell Metabolism,2019,29(5):1206-1216.
[11] ICARD P,LINCET H,WU Z,et al.The key role of Warburg effect in SARS-CoV-2 replication and associated inflammatory response[J].Biochimie,2021,180:169-177.
[12] 杨秀文,陆剑云,卢紫欣,等.糖代谢在肠道病毒EV71复制中的作用研究[J].中国病原生物学杂志,2022,17(2):143-148. YANG X W,LU J Y,LU Z X,et al.The role of glucose metabolism in the replication of Enterovirus EV71[J].Journal of Pathogen Biology,2022,17(2):143-148.(in Chinese)
[13] PURDY J G,SHENK T,RABINOWITZ J D.Fatty acid elongase 7 catalyzes lipidome remodeling essential for Human cytomegalovirus replication[J].Cell Reports,2015,10(8):1375-1385.
[14] OKAMURA H,NIO Y,AKAHORI Y,et al.Fatty acid biosynthesis is involved in the production of Hepatitis B virus particles[J].Biochemical and Biophysical Research Communications,2016,475(1):87-92.
[15] YAMANE D,HAYASHI Y,MATSUMOTO M,et al.FADS2-dependent fatty acid desaturation dictates cellular sensitivity to ferroptosis and permissiveness for Hepatitis C virus replication[J].Cell Chemical Biology,2022,29(5):799-810.
[16] KULKARNI M M,RATCLIFF A N,BHAT M,et al.Cellular fatty acid synthase is required for late stages of HIV-1 replication[J].Retrovirology,2017,14(1):45.
[17] MOSER T S,SCHIEFFER D,CHERRY S.AMP-activated kinase restricts Rift Valley fever virus infection by inhibiting fatty acid synthesis[J].PLoS Pathogens,2012,8(4):e1002661.
[18] ZHANG M,HAN X,OSTERRIEDER K,et al.Palmitoylation of the envelope membrane proteins GP5 and M of Porcine reproductive and respiratory syndrome virus is essential for virus growth[J].PLoS Pathogens,2021,17(4):e1009554.
[19] 龙思文.脂质代谢在猪繁殖与呼吸综合征病毒感染中的作用研究[D].武汉:华中农业大学,2019. LONG S W.The role of lipid metabolism in Porcine reproduction and respiratory syndrome virus infection[D].Wuhan:Huazhong Agricultural University,2019.(in Chinese)
[20] LONG S,ZHOU Y,BAI D,et al.Fatty acids regulate Porcine reproductive and respiratory syndrome virus infection via the AMPK-ACC1 signaling pathway[J].Viruses,2019,11(12):1145.
[21] 熊玉剑.猪PRDX5在PRRSV调控AMPK信号通路中的作用及机制研究[D].武汉:华中农业大学,2022. XIONG Y J.Study of effects and mechanisms of pig PRDX5 in the regulation of AMPK signaling pathway during Porcine reproductive and respiratory syndrome virus infection[D].Wuhan:Huazhong Agricultural University,2022.(in Chinese)
[22] YANG L,WEN J,ZHANG Y,et al.The antiviral activity of caprylic monoglyceride against Porcine reproductive and respiratory syndrome virus in vitro and in vivo[J].Molecules,2022,27(21):7263.
[23] 蓝俊虹.α-单月桂酸甘油酯对猪繁殖与呼吸综合征病毒抑制机制的探究[D].杭州:浙江农林大学,2021. LAN J H.Inhibitory mechanism of α-glycerol monolaurate on Porcine reproductive and respiratory syndrome virus[D].Hangzhou:Zhejiang Agricultural and Forestry University,2021.(in Chinese)
[24] BI Y,GUO X K,ZHAO H,et al.Highly pathogenic Porcine reproductive and respiratory syndrome virus induces prostaglandin E₂ production through cyclooxygenase 1,which is dependent on the ERK1/2-p-C/EBP-beta pathway[J].Journal of Virology,2014,88(5):2810-2820.
[25] DU L,WANG H,LIU F,et al.NSP2 is important for highly pathogenic Porcine reproductive and respiratory syndrome virus to trigger high fever-related COX-2-PGE2 pathway in pigs[J]. Frontiers in Immunology,2021,12:657071.
[26] SUN Y,XIAO S,WANG D,et al.Cellular membrane cholesterol is required for Porcine reproductive and respiratory syndrome virus entry and release in Marc-145 cells[J].Science China-Life Sciences,2011,54(11):1011-1018.
[27] HUANG L,ZHANG Y P,YU Y L,et al.Role of lipid rafts in Porcine reproductive and respiratory syndrome virus infection in Marc-145 cells[J].Biochemical and Biophysical Research Communications,2011,414(3):545-550.
[28] DONG H,ZHOU L,GE X,et al.Porcine reproductive and respiratory syndrome virus NSP1beta and NSP11 antagonize the antiviral activity of cholesterol-25-hydroxylase via lysosomal degradation[J].Veterinary Microbiology,2018,223:134-143.
[29] ZHAO J,CHEN J,LI M,et al.Multifaceted functions of CH25H and 25HC to modulate the lipid metabolism,immune responses,and broadly antiviral activities[J].Viruses,2020,12(7):727.
[30] SONG Z,ZHANG Q,LIU X,et al.Cholesterol 25-hydroxylase is an interferon-inducible factor that protects against Porcine reproductive and respiratory syndrome virus infection[J].Veterinary Microbiology,2017,210:153-161.
[31] KE W,FANG L,TAO R,et al.Porcine reproductive and respiratory syndrome virus E protein degrades porcine cholesterol 25-hydroxylase via the ubiquitin-proteasome pathway[J].Journal of Virology,2019,93(20):e719-e767.
[32] DONG H,ZHOU L,GE X,et al.Antiviral effect of 25-hydroxycholesterol against Porcine reproductive and respiratory syndrome virus in vitro[J].Antiviral Therapy,2018,23(5):395-404.
[33] SONG Z,BAI J,NAUWYNCK H,et al.25-hydroxycholesterol provides antiviral protection against highly pathogenic Porcine reproductive and respiratory syndrome virus in swine[J].Veterinary Microbiology,2019,231:63-70.
[34] LI Y J,ZHU P,LIANG Y,et al.Hepatitis B virus induces expression of cholesterol metabolism-related genes via TLR2 in HepG2 cells[J].World Journal of Gastroenterology,2013,19(14):2262-2269.
[35] HSU C S,LIU W L,LI Q,et al.Hepatitis C virus genotypes 1-3 infections regulate lipogenic signaling and suppress cholesterol biosynthesis in hepatocytes[J].Journal of the Formosan Medical Association,2020,119(9):1382-1395.
[36] GUO N,ZHANG N,YAN L,et al.Down-regulation of single-stranded DNA-binding protein 1 expression induced by HCMV infection promotes lipid accumulation in cells[J].Brazilian Journal of Medical and Biological Research,2017,50(11):e6389.
[37] SOTO-ACOSTA R,BAUTISTA-CARBAJAL P,CERVANTES-SALAZAR M,et al.DENV up-regulates the HMG-CoA reductase activity through the impairment of AMPK phosphorylation:A potential antiviral target[J].PLoS Pathogens,2017,13(4):e1006257.
[38] SERQUINA A,KAMBACH D M,SARKER O,et al.Viral microRNAs repress the cholesterol pathway,and 25-hydroxycholesterol inhibits infection[J].mBio,2017,8(4):e517-e576.
[39] KE W,ZHOU Y,LAI Y,et al.Porcine reproductive and respiratory syndrome virus nsp4 positively regulates cellular cholesterol to inhibit type Ⅰ interferon production[J].Redox Biology,2022,49:102207.
[40] 张玉娇.PRRSV强弱毒感染PAM细胞的差异膜蛋白分析及其作用机制的研究[D].北京:中国农业科学院,2018. ZHANG Y J.Analysis of differentially expressed membrane proteins of PAMs infected with highly pathogenic and attenuated PRRSVs[D].Beijing:Chinese Academy of Agricultural Sciences,2018.(in Chinese)
[41] 张玉娇.膜蛋白PCSK9和BST2抑制PRRSV复制的机制研究[D].北京:中国农业科学院,2021. ZHANG Y J.The mechanism of membrane proteins PCSK9 and BST2 inhibiting PRRSV replication[D].Beijing:Chinese Academy of Agricultural Sciences,2021.(in Chinese)
[42] 姚伦.伪狂犬病毒感染猪肺泡巨噬细胞代谢组学研究及靶向树突状细胞的新型疫苗构建[D].武汉:华中农业大学,2022. YAO L.Metabonomics study of Pseudorabies virus infected porcine alveolar macrophage and construction of a novel vaccine by targeting dendritic cells[D].Wuhan:Huazhong Agricultural University,2022.(in Chinese)
[43] VIAL T,TAN W L,DEHARO E,et al.Mosquito metabolomics reveal that Dengue virus replication requires phospholipid reconfiguration via the remodeling cycle[J].Proceedings of the National Academy of Sciences of the United States of America,2020,117(44):27627-27636.
[44] LEE S M,KLEIBOEKER S B.Porcine reproductive and respiratory syndrome virus induces apoptosis through a mitochondria-mediated pathway[J]. Virology,2007,365(2):419-434.
[45] 魏欣.猪繁殖与呼吸综合征病毒利用病毒凋亡模拟入侵宿主细胞的分子机制研究[D].郑州:河南农业大学,2020. WEI X.Investigation on the viral apoptotic mimicry utilized by Porcine reproductive and respiratory syndrome virus to invade host cells[D].Zhengzhou:Henan Agricultural University,2020.(in Chinese)
[46] WANG X,ZHANG H,ABEL A M,et al.Role of phosphatidylinositol 3-kinase (PI3K) and Akt1 kinase in Porcine reproductive and respiratory syndrome virus (PRRSV) replication[J].Archives of Virology,2014,159(8):2091-2096.
[47] SHEN H H,ZHAO Q,WEN Y P,et al.Porcine reproductive and respiratory syndrome virus upregulates SMPDL3B to promote viral replication by modulating lipid metabolism[J].iScience,2023,26(8):107450.
[48] 魏巍.PRRSV感染骨髓组织实时定量PCR内参基因的选择及ASAH1基因表达影响研究[D].太谷:山西农业大学,2014. WEI W.Reference gene selection of qRT-PCR and effects on ASAH1 level in PRRSV infected bone marrow[D].Taigu:Shanxi Agricultural University,2014.(in Chinese)
[49] CRAWFORD S E,DESSELBERGER U.Lipid droplets form complexes with viroplasms and are crucial for Rotavirus replication[J].Current Opinion in Virology,2016,19:11-15.
[50] SAMSA M M,MONDOTTE J A,IGLESIAS N G,et al.Dengue virus capsid protein usurps lipid droplets for viral particle formation[J].PLoS Pathogens,2009,5(10):e1000632.
[51] HERKER E,HARRIS C,HERNANDEZ C,et al.Efficient Hepatitis C virus particle formation requires diacylglycerol acyltransferase-1[J].Nature Medicine,2010,16(11):1295-1298.
[52] ZHAO J,ZENG Z,CHEN Y,et al.Lipid droplets are beneficial for Rabies virus replication by facilitating viral budding[J].Journal of Virology,2022,96(2):e0147321.
[53] WANG J,LIU J Y,SHAO K Y,et al.Porcine reproductive and respiratory syndrome virus activates lipophagy to facilitate viral replication through downregulation of NDRG1 expression[J].Journal of Virology,2019,93(17):e519-e526.
[54] YU P W,FU P F,ZENG L,et al.EGCG restricts PRRSV proliferation by disturbing lipid metabolism[J].Microbiology Spectrum,2022,10(2):e227621.
[55] 韩莹倩.Rab18介导宿主细胞脂质代谢参与猪繁殖与呼吸综合征病毒复制的分子机制[D].郑州:河南农业大学,2019. HAN Y Q.Molecular mechanism study of the Rab18-mediated host-cell lipid metabolism responses to Porcine reproductive and respiratory syndrome virus infection[D].Zhengzhou:Henan Agricultural University,2019.(in Chinese)
[56] YANG Y,LUO Y,YI S,et al.Porcine reproductive and respiratory syndrome virus regulates lipid droplet accumulation in lipid metabolic pathways to promote viral replication[J].Virus Research,2023,333:199139.
[57] REGEN S L.The origin of lipid rafts[J].Biochemistry,2020,59(49):4617-4621.
[58] KULKARNI R,WIEMER E A C,CHANG W.Role of lipid rafts in pathogen-host interaction—A mini review[J].Frontiers in Immunology,2022,12:815020.
[59] GEE Y J,SEA Y L,LAL S K.Viral modulation of lipid rafts and their potential as putative antiviral targets[J].Reviews in Medical Virology,2023,33(2):e2413.
[60] VERMA D K G D.Host lipid rafts play a major role in binding and endocytosis of Influenza A virus[J].Viruses,2018,10(11):650.
[61] BAKILLAH A,HEJJI F A,ALMASAUD A,et al.Lipid raft integrity and cellular cholesterol homeostasis are critical for SARS-CoV-2 entry into cells[J].Nutrients,2022,14(16):3417.
[62] PERUZZU D,AMENDOLA A,VENTURI G,et al.Zika virus exploits lipid rafts to infect host cells[J]. Viruses,2022,14(9):2059.
[63] JIN C,CHE B,GUO Z,et al.Single virus tracking of Ebola virus entry through lipid rafts in living host cells[J]. Biosafety and Health,2020,2(1):25-31.
[64] YANG Q,ZHANG Q,TANG J,et al.Lipid rafts both in cellular membrane and viral envelope are critical for PRRSV efficient infection[J]. Virology,2015,484:170-180.
[65] DU Y,PATTNAIK A K,SONG C,et al.Glycosyl-phosphatidylinositol (GPI)-anchored membrane association of the Porcine reproductive and respiratory syndrome virus GP4 glycoprotein and its co-localization with CD163 in lipid rafts[J]. Virology,2012,424(1):18-32.
[66] 孙颖.脂筏在猪繁殖与呼吸综合征病毒感染中作用的初步探讨[D].武汉:华中农业大学,2009. SUN Y.Study on the effects of lipid raft on the infection of Porcine reproductive and respiratory syndrome virus[D].Wuhan:Huazhong Agricultural University,2009.(in Chinese)
[67] LEE Y R,WU S Y,CHEN R Y,et al.Regulation of autophagy,glucose uptake,and glycolysis under Dengue virus infection[J].The Kaohsiung Journal of Medical Sciences,2020,36(11):911-919.
[68] REN L,ZHANG W,ZHANG J,et al.Influenza A virus (H1N1) infection induces glycolysis to facilitate viral replication[J].Virologica Sinica,2021,36(6):1532-1542.
[69] JUNG G S,JEON J H,CHOI Y K,et al.Pyruvate dehydrogenase kinase regulates Hepatitis C virus replication[J].Scientific Reports,2016,6:30846.
[70] THAI M,GRAHAM N A,BRAAS D,et al.Adenovirus E4ORF1-induced MYC activation promotes host cell anabolic glucose metabolism and virus replication[J].Cell Metabolism,2014,19(4):694-701.
[71] LIU X,LIU X,BAI J,et al.Glyceraldehyde-3-phosphate dehydrogenase restricted in cytoplasmic location by viral GP5 facilitates Porcine reproductive and respiratory syndrome virus replication via its glycolytic activity[J].Journal of Virology,2021,95(18):e21021.
[72] ZHANG L,LIU X,MAO J,et al.Porcine reproductive and respiratory syndrome virus-mediated lactate facilitates virus replication by targeting MAVS[J].Veterinary Microbiology,2023,284:109846.
[73] 毛健,刘雪威,刘星,等.乳酸脱氢酶在猪繁殖与呼吸综合征病毒复制中的作用[J].中国兽医科学,2021,51(10):1264-1269. MAO J,LIU X W,LIU X,et al.The role of lactate dehydrogenase in the replication of Porcine reproductive and respiratory syndrome virus[J].Chinese Veterinary Science,2021,51(10):1264-1269.(in Chinese)
[74] PANG Y,WANG Y,LI C,et al.Itaconate derivative 4-OI inhibits PRRSV proliferation and associated inflammatory response[J].Virology,2022,577:84-90.
[75] HEATON N S,RANDALL G.Multifaceted roles for lipids in viral infection[J].Trends in Microbiology,2011,19(7):368-375.