细胞自噬在冠状病毒感染中的作用Role of Autophagy in Coronavirus Infection
曾思莹;徐志超;薛春宜;曹永长;
摘要(Abstract):
细胞自噬是一种保守的广泛存在于真核细胞内的溶酶体依赖性分解代谢途径,其通过形成双层膜结构的自噬体降解蛋白质和细胞器,参与物质循环和稳态维持。同时,自噬也能作为机体免疫防御的一部分发挥抗病毒的作用,或是被病毒利用以促进其自身增殖。冠状病毒是一种有囊膜的单股正链RNA病毒,能够诱导双层膜囊泡形成转录复合物,进一步指导病毒基因组的合成。研究表明多个冠状病毒成员能够诱导自噬发生,自噬参与了病毒增殖的多个环节。本文拟对细胞自噬的概况及作用、自噬在病毒感染特别是冠状病毒感染中的作用进行综述,以期为揭示冠状病毒的致病机理提供参考,并为开发冠状病毒的治疗方案提供新思路。
关键词(KeyWords): 自噬;冠状病毒;免疫反应
基金项目(Foundation): 有害生物控制与资源利用国家重点实验室应急项目(项目号:09020-32030002),题目:植物提取物治疗冠状病毒感染的成药性研究~~
作者(Author): 曾思莹;徐志超;薛春宜;曹永长;
Email:
DOI: 10.13242/j.cnki.bingduxuebao.003868
参考文献(References):
- [1]Luo H,Wong J,Wong B.Protein degradation systems in viral myocarditis leading to dilated cardiomyopathy[J].Cardiovasc Res,2010,85(2):347-356.
- [2]Levine B.Eating oneself and uninvited guests:autophagy-related pathways in cellular defense[J].Cell,2005,120(2):159-162.
- [3]Levine B,Mizushima N,Virgin H W.Autophagy in immunity and inflammation[J].Nature,2011,469(7330):323-335.
- [4]Levine B,Kroemer G.Autophagy in the pathogenesis of disease[J].Cell,2008,132(1):27-42.
- [5]Choi Y,Bowman J W,Jung J U.Autophagy during viral infection-a double-edged sword[J].Nat Rev Microbiol,2018,16(6):341-354.
- [6]Booth L A,Tavallai S,Hamed H A,Cruickshanks N,Dent P.The role of cell signalling in the crosstalk between autophagy and apoptosis[J].Cell Signal,2014,26(3):549-555.
- [7]Levine B,Kroemer G.Biological Functions of Autophagy Genes:A Disease Perspective[J].Cell,2019,176(1-2):11-42.
- [8]Wang C W,Klionsky D J.The molecular mechanism of autophagy[J].Mol Med,2003,9(3-4):65-76.
- [9]Klionsky D J,Cregg J M,Dunn W J,Emr S D,Sakai Y,Sandoval I V,Sibirny A,Subramani S,Thumm M,Veenhuis M,Ohsumi Y.A unified nomenclature for yeast autophagy-related genes[J].Dev Cell,2003,5(4):539-545.
- [10]Hosokawa N,Sasaki T,Iemura S,Natsume T,Hara T,Mizushima N.Atg101,a novel mammalian autophagy protein interacting with Atg13[J].Autophagy,2009,5(7):973-979.
- [11]Hosokawa N,Hara T,Kaizuka T,Kishi C,Takamura A,Miura Y,Iemura S,Natsume T,Takehana K,Yamada N,Guan J L,Oshiro N,Mizushima N.Nutrient-dependent m TORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy[J].Mol Biol Cell,2009,20(7):1981-1991.
- [12]Kim Y M,Jung C H,Seo M,Kim E K,Park J M,Bae S S,Kim D H.m TORC1 phosphorylates UVRAG to negatively regulate autophagosome and endosome maturation[J].Mol Cell,2015,57(2):207-218.
- [13]Pattingre S,Tassa A,Qu X,Garuti R,Liang X H,Mizushima N,Packer M,Schneider M D,Levine B.Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy[J].Cell,2005,122(6):927-939.
- [14]Shpilka T,Weidberg H,Pietrokovski S,Elazar Z.Atg8:an autophagy-related ubiquitin-like protein family[J].Genome Biol,2011,12(7):226.
- [15]Tsuboyama K,Koyama-Honda I,Sakamaki Y,Koike M,Morishita H,Mizushima N.The ATG conjugation systems are important for degradation of the inner autophagosomal membrane[J].Science,2016,354(6315):1036-1041.
- [16]Mizushima N,Yoshimori T,Ohsumi Y.The role of Atg proteins in autophagosome formation[J].Annu Rev Cell Dev Biol,2011,27:107-132.
- [17]Nakatogawa H,Ichimura Y,Ohsumi Y.Atg8,a ubiquitin-like protein required for autophagosome formation,mediates membrane tethering and hemifusion[J].Cell,2007,130(1):165-178.
- [18]Wild P,Farhan H,Mcewan D G,Wagner S,Rogov VV,Brady N R,Richter B,Korac J,Waidmann O,Choudhary C,Dotsch V,Bumann D,Dikic I.Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth[J].Science,2011,333(6039):228-233.
- [19]Kirkin V,Lamark T,Sou Y S,Bjorkoy G,Nunn J L,Bruun J A,Shvets E,Mcewan D G,Clausen T H,Wild P,Bilusic I,Theurillat J P,Overvatn A,Ishii T,Elazar Z,Komatsu M,Dikic I,Johansen T.A role for NBR1 in autophagosomal degradation of ubiquitinated substrates[J].Mol Cell,2009,33(4):505-516.
- [20]Kawaguchi Y,Kovacs J J,Mclaurin A,Vance J M,Ito A,Yao T P.The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress[J].Cell,2003,115(6):727-738.
- [21]Kawai T,Akira S.The role of pattern-recognition receptors in innate immunity:update on Toll-like receptors[J].Nat Immunol,2010,11(5):373-384.
- [22]Stanifer M L,Pervolaraki K,Boulant S.Differential Regulation of Type I and Type III Interferon Signaling[J].Int J Mol Sci,2019,20(6).
- [23]Lee M S,Kim Y J.Signaling pathways downstream of pattern-recognition receptors and their cross talk[J].Annu Rev Biochem,2007,76:447-480.
- [24]Zalckvar E,Berissi H,Eisenstein M,Kimchi A.Phosphorylation of Beclin 1 by DAP-kinase promotes autophagy by weakening its interactions with Bcl-2 and Bcl-XL[J].Autophagy,2009,5(5):720-722.
- [25]Chen G Y,Yang H J,Lu C H,Chao Y C,Hwang SM,Chen C L,Lo K W,Sung L Y,Luo W Y,Tuan HY,Hu Y C.Simultaneous induction of autophagy and toll-like receptor signaling pathways by graphene oxide[J].Biomaterials,2012,33(27):6559-6569.
- [26]Song J,Hu Y,Li J,Zheng H,Wang J,Guo L,Shi H,Liu L.Suppression of the toll-like receptor 7-dependent type I interferon production pathway by autophagy resulting from enterovirus 71 and coxsackievirus A16 infections facilitates their replication[J].Arch Virol,2018,163(1):135-144.
- [27]Chiang J J,Davis M E,Gack M U.Regulation of RIG-I-like receptor signaling by host and viral proteins[J].Cytokine Growth Factor Rev,2014,25(5):491-505.
- [28]Lee N R,Ban J,Lee N J,Yi C M,Choi J Y,Kim H,Lee J K,Seong J,Cho N H,Jung J U,Inn K S.Activation of RIG-I-Mediated Antiviral Signaling Triggers Autophagy Through the MAVS-TRAF6-Beclin-1 Signaling Axis[J].Front Immunol,2018,9:2096.
- [29]Du Y,Duan T,Feng Y,Liu Q,Lin M,Cui J,Wang R F.LRRC25 inhibits type I IFN signaling by targeting ISG15-associated RIG-I for autophagic degradation[J].EMBO J,2018,37(3):351-366.
- [30]Gui X,Yang H,Li T,Tan X,Shi P,Li M,Du F,Chen Z J.Autophagy induction via STING trafficking is a primordial function of the c GAS pathway[J].Nature,2019,567(7747):262-266.
- [31]Liang Q,Seo G J,Choi Y J,Kwak M J,Ge J,Rodgers M A,Shi M,Leslie B J,Hopfner K P,Ha T,Oh B H,Jung J U.Crosstalk between the c GAS DNAsensor and Beclin-1 autophagy protein shapes innate antimicrobial immune responses[J].Cell Host Microbe,2014,15(2):228-238.
- [32]Loi M,Muller A,Steinbach K,Niven J,Barreira D SR,Paul P,Ligeon L A,Caruso A,Albrecht R A,Becker A C,Annaheim N,Nowag H,Dengjel J,Garcia-Sastre A,Merkler D,Munz C,Gannage M.Macroautophagy Proteins Control MHC Class I Levels on Dendritic Cells and Shape Anti-viral CD8(+)T Cell Responses[J].Cell Rep,2016,15(5):1076-1087.
- [33]Dengjel J,Schoor O,Fischer R,Reich M,Kraus M,Muller M,Kreymborg K,Altenberend F,Brandenburg J,Kalbacher H,Brock R,Driessen C,Rammensee HG,Stevanovic S.Autophagy promotes MHC class IIpresentation of peptides from intracellular source proteins[J].Proc Natl Acad Sci U S A,2005,102(22):7922-7927.
- [34]Coulon P G,Richetta C,Rouers A,Blanchet F P,Urrutia A,Guerbois M,Piguet V,Theodorou I,Bet A,Schwartz O,Tangy F,Graff-Dubois S,Cardinaud S,Moris A.HIV-Infected Dendritic Cells Present Endogenous MHC Class II-Restricted Antigens to HIV-Specific CD4+T Cells[J].J Immunol,2016,197(2):517-532.
- [35]English L,Chemali M,Desjardins M.Nuclear membrane-derived autophagy,a novel process that participates in the presentation of endogenous viral antigens during HSV-1 infection[J].Autophagy,2009,5(7):1026-1029.
- [36]Stephenson L M,Miller B C,Ng A,Eisenberg J,Zhao Z,Cadwell K,Graham D B,Mizushima N N,Xavier R,Virgin H W,Swat W.Identification of Atg5-dependent transcriptional changes and increases in mitochondrial mass in Atg5-deficient T lymphocytes[J].Autophagy,2009,5(5):625-635.
- [37]Xu X,Araki K,Li S,Han J H,Ye L,Tan W G,Konieczny B T,Bruinsma M W,Martinez J,Pearce EL,Green D R,Jones D P,Virgin H W,Ahmed R.Autophagy is essential for effector CD8(+) T cell survival and memory formation[J].Nat Immunol,2014,15(12):1152-1161.
- [38]Puleston D J,Zhang H,Powell T J,Lipina E,Sims S,Panse I,Watson A S,Cerundolo V,Townsend A R,Klenerman P,Simon A K.Autophagy is a critical regulator of memory CD8(+) T cell formation[J].Elife,2014,3.
- [39]Fehr A R,Perlman S.Coronaviruses:an overview of their replication and pathogenesis[J].Methods Mol Biol,2015,1282:1-23.
- [40]Rubio R M,Mohr I.Inhibition of ULK1 and Beclin1 by an alpha-herpesvirus Akt-like Ser/Thr kinase limits autophagy to stimulate virus replication[J].Proc Natl Acad Sci U S A,2019.
- [41]Roldan J S,Candurra N A,Colombo M I,Delgui L R.Junin Virus Promotes Autophagy To Facilitate the Virus Life Cycle[J].J Virol,2019,93(15).
- [42]Prentice E,Jerome W G,Yoshimori T,Mizushima N,Denison M R.Coronavirus replication complex formation utilizes components of cellular autophagy[J].JBiol Chem,2004,279(11):10136-10141.
- [43]Prentice E,Mcauliffe J,Lu X,Subbarao K,Denison MR.Identification and characterization of severe acute respiratory syndrome coronavirus replicase proteins[J].JVirol,2004,78(18):9977-9986.
- [44]Zhao Z,Thackray L B,Miller B C,Lynn T M,Becker M M,Ward E,Mizushima N N,Denison M R,Virgin H T.Coronavirus replication does not require the autophagy gene ATG5[J].Autophagy,2007,3(6):581-585.
- [45]Snijder E J,van der Meer Y,Zevenhoven-Dobbe J,Onderwater J J,van der Meulen J,Koerten H K,Mommaas A M.Ultrastructure and origin of membrane vesicles associated with the severe acute respiratory syndrome coronavirus replication complex[J].J Virol,2006,80(12):5927-5940.
- [46]Schneider M,Ackermann K,Stuart M,Wex C,Protzer U,Schatzl H M,Gilch S.Severe acute respiratory syndrome coronavirus replication is severely impaired by MG132 due to proteasome-independent inhibition of M-calpain[J].J Virol,2012,86(18):10112-10122.
- [47]Fung T S,Liu D X.The ER stress sensor IRE1 and MAP kinase ERK modulate autophagy induction in cells infected with coronavirus infectious bronchitis virus[J].Virology,2019,533:34-44.
- [48]Maier H J,Cottam E M,Stevenson-Leggett P,Wilkinson J A,Harte C J,Wileman T,Britton P.Visualizing the autophagy pathway in avian cells and its application to studying infectious bronchitis virus[J].Autophagy,2013,9(4):496-509.
- [49]Zhu L,Mou C,Yang X,Lin J,Yang Q.Mitophagy in TGEV infection counteracts oxidative stress and apoptosis[J].Oncotarget,2016,7(19):27122-27141.
- [50]Min J S,Kim D E,Jin Y H,Kwon S.Kurarinone Inhibits HCo V-OC43 Infection by Impairing the Virus-Induced Autophagic Flux in MRC-5 Human Lung Cells[J].J Clin Med,2020,9(7).
- [51]Reggiori F,Monastyrska I,Verheije M H,Cali T,Ulasli M,Bianchi S,Bernasconi R,de Haan C A,Molinari M.Coronaviruses Hijack the LC3-I-positive EDEMosomes,ER-derived vesicles exporting short-lived ERAD regulators,for replication[J].Cell Host Microbe,2010,7(6):500-508.
- [52]Ko S,Gu M J,Kim C G,Kye Y C,Lim Y,Lee J E,Park B C,Chu H,Han S H,Yun C H.Rapamycin-induced autophagy restricts porcine epidemic diarrhea virus infectivity in porcine intestinal epithelial cells[J].Antiviral Res,2017,146:86-95.
- [53]Kong N,Shan T,Wang H,Jiao Y,Zuo Y,Li L,Tong W,Yu L,Jiang Y,Zhou Y,Li G,Gao F,Yu H,Zheng H,Tong G.BST2 suppresses porcine epidemic diarrhea virus replication by targeting and degrading virus nucleocapsid protein with selective autophagy[J].Autophagy,2019:1-16.
- [54]Guo L,Yu H,Gu W,Luo X,Li R,Zhang J,Xu Y,Yang L,Shen N,Feng L,Wang Y.Autophagy Negatively Regulates Transmissible Gastroenteritis Virus Replication[J].Sci Rep,2016,6:23864.
- [55]Cottam E M,Whelband M C,Wileman T.Coronavirus NSP6 restricts autophagosome expansion[J].Autophagy,2014,10(8):1426-1441.
- [56]Chen X,Wang K,Xing Y,Tu J,Yang X,Zhao Q,Li K,Chen Z.Coronavirus membrane-associated papain-like proteases induce autophagy through interacting with Beclin1 to negatively regulate antiviral innate immunity[J].Protein Cell,2014,5(12):912-927.
- [57]Gassen N C,Niemeyer D,Muth D,Corman V M,Martinelli S,Gassen A,Hafner K,Papies J,Mosbauer K,Zellner A,Zannas A S,Herrmann A,Holsboer F,Brack-Werner R,Boshart M,Muller-Myhsok B,Drosten C,Muller M A,Rein T.SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection[J].Nat Commun,2019,10(1):5770.
- [58]Shojaei S,Suresh M,Klionsky D J,Labouta H I,Ghavami S.Autophagy and SARS-Co V-2 infection:Apossible smart targeting of the autophagy pathway[J].Virulence,2020,11(1):805-810.
- [59]Gao J,Tian Z,Yang X.Breakthrough:Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies[J].Biosci Trends,2020,14(1):72-73.
- [60]Yu B,Li C,Chen P,Zhou N,Wang L,Li J,Jiang H,Wang D W.Low dose of hydroxychloroquine reduces fatality of critically ill patients with COVID-19[J].Sci China Life Sci,2020,63(10):1515-1521.
- [61]Maisonnasse P,Guedj J,Contreras V,Behillil S,Solas C,Marlin R,Naninck T,Pizzorno A,Lemaitre J,Goncalves A,Kahlaoui N,Terrier O,Fang R,Enouf V,Dereuddre-Bosquet N,Brisebarre A,Touret F,Chapon C,Hoen B,Lina B,Calatrava M R,van der Werf S,de Lamballerie X,Le Grand R.Hydroxychloroquine use against SARS-Co V-2 infection in non-human primates[J].Nature,2020,585(7826):584-587.
- [62]Mahevas M,Tran V T,Roumier M,Chabrol A,Paule R,Guillaud C,Fois E,Lepeule R,Szwebel T A,Lescure F X,Schlemmer F,Matignon M,Khellaf M,Crickx E,Terrier B,Morbieu C,Legendre P,Dang J,Schoindre Y,Pawlotsky J M,Michel M,Perrodeau E,Carlier N,Roche N,de Lastours V,Ourghanlian C,Kerneis S,Menager P,Mouthon L,Audureau E,Ravaud P,Godeau B,Gallien S,Costedoat-Chalumeau N.Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen:observational comparative study using routine care data[J].BMJ,2020,369:m1844.
- [63]Edelstein C L,Venkatachalam M A,Dong Z.Autophagy inhibition by chloroquine and hydroxychloroquine could adversely affect acute kidney injury and other organ injury in critically ill patients with COVID-19[J].Kidney Int,2020,98(1):234-235.
- [64]Bedi O,Dhawan V,Sharma P L,Kumar P.Pleiotropic effects of statins:new therapeutic targets in drug design[J].Naunyn Schmiedebergs Arch Pharmacol,2016,389(7):695-712.
- [65]Jury E C,Isenberg D A,Mauri C,Ehrenstein M R.Atorvastatin restores Lck expression and lipid raft-associated signaling in T cells from patients with systemic lupus erythematosus[J].J Immunol,2006,177(10):7416-7422.
- [66]South A M,Diz D I,Chappell M C.COVID-19,ACE2,and the cardiovascular consequences[J].Am JPhysiol Heart Circ Physiol,2020,318(5):H1084-H1090.
- [67]Sasidhar M V,Chevooru S K,Eickelberg O,Hartung H P,Neuhaus O.Downregulation of monocytic differentiation via modulation of CD147 by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors[J/OL].PLo S One,2017,12(12):e189701.
- [68]Zhang J,Yang Z,Xie L,Xu L,Xu D,Liu X.Statins,autophagy and cancer metastasis[J].Int J Biochem Cell Biol,2013,45(3):745-752.
- [69]Yang Z,Su Z,Dewitt J P,Xie L,Chen Y,Li X,Han L,Li D,Xia J,Zhang Y,Yang Y,Jin C,Zhang J,Li S,Li K,Zhang Z,Qu X,He Z,Chen Y,Shen Y,Ren M,Yuan Z.Fluvastatin Prevents Lung Adenocarcinoma Bone Metastasis by Triggering Autophagy[J].EBio Medicine,2017,19:49-59.
- [70]Gao S,Zhang Z M,Shen Z L,Gao K,Chang L,Guo Y,Li Z,Wang W,Wang A M.Atorvastatin activates autophagy and promotes neurological function recovery after spinal cord injury[J].Neural Regen Res,2016,11(6):977-982.
- [71]Gorshkov K,Chen C Z,Bostwick R,Rasmussen L,Xu M,Pradhan M,Tran B N,Zhu W,Shamim K,Huang W,Hu X,Shen M,Klumpp-Thomas C,Itkin Z,Shinn P,Simeonov A,Michael S,Hall M D,Lo DC,Zheng W.The SARS-Co V-2 cytopathic effect is blocked with autophagy modulators[J].bio Rxiv,2020.
- [72]Halfon P,Bestion E,Zandi K,Andreani J,Baudoin JP,La Scola B,Mege J L,Mezouar S,Schinazi R F.GNS561 exhibits potent in vitro antiviral activity against SARS-Co V-2 through autophagy inhibition[J].bio Rxiv,2020.
- [73]Guo X,Zhang M,Zhang X,Tan X,Guo H,Zeng W,Yan G,Memon A M,Li Z,Zhu Y,Zhang B,Ku X,Wu M,Fan S,He Q.Porcine Epidemic Diarrhea Virus Induces Autophagy to Benefit Its Replication[J].Viruses,2017,9(3).