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自噬是广泛存在于真核细胞内的一种溶酶体依赖性降解途径,在维持细胞存活、更新、物质再利用和内环境稳定中起着重要作用。目前已经发现大量新的自噬相关基因,同时发现自噬在病毒感染过程中发挥着重要的抗病毒作用:自噬可以将胞质中的病毒转运到溶酶体中,降解病毒;也可以将病毒核酸转运至胞内感受器上激活天然免疫;还可以将病毒抗原递呈给MHCⅡ类分子激活适应性免疫。自噬参与胞内微生物感染具有双重作用。一方面,自噬能够降解入侵的微生物,即以异源吞噬(xenophagy)的方式清除胞内的病原体;另一方面,有些微生物能够通过某些机制逃避自噬而利于自身存活。本文就细胞自噬及其与不同病毒感染关系的最新研究进展进行综述。
Abstract：Autophagy is a catabolic process including self-degradation of intracellular components via the lysosomal machinery.The biological behavior can be regarded as defense mechanism,maintaining the cell growth,metabolism and homeostasis etc.To date,plenty of autophagy related genes have been identified.In addition,it has been recognized that autophagy plays important roles in the context of virus infection: it can transport viruses from cytoplasm to lysosome to degrade viruses;it can transfer viral nucleic acid to intracellular sensors to activate innate immunity;it can also present viral antigens to MHC class II molecules to activate adaptive immune responses.Autophagy may serve as a double-edged sword to intracellular pathogens.On one side,autophagy may degrade and clear invading microorganisms by xenophagy;on the other side,some microorganisms may develop mechanisms to escape from autophagy for their survival.In this paper,the notion of autophay and the function of autophagy related genes are reviewed.Furthermore,the association of autophagy with a variety of viruses is discussed.
[1]Czaja M J.Autophagy in health and disease.2.Regual-tion of lipid metabolism and storage by autophagy:pathophysiological implications[J].Am J Physiol CellPhysiol,2010,298(5):973-978.
[2]Singh R,Kaushik S,Wang Y,et al.Autophagy regulateslipid metabolism[J].Nature,2009,458(7242):1131-1135.
[3]Levine B,Mizushima N,Virgin H W.Autophagy inimmunity and inflammation[J].Nature,2011,469(7330):323-335.
[4]Deretic V.Autophagy in immunity and cell-autonomousdefense against intracellular microbes[J].Immunol Rev,2011,240(1):92-104.
[5]Crotzer V L,Blum J S.Autophagy and intracellularsurveillance:Modulating MHC class II antigen presen-tation with stress[J].Proc Natl Acad Sci USA,2005,102(22):7779-7780.
[6]Majeski A E,Fred Dice J F.Mechanisms of chaperonemediated autophagy[J].Int J Biochem Cell Biol,2004,36(12):2435-2444.
[7]Levine B,Yuan J Y.Autophagy in cell death:an inno-cent eonvict[J].Clin Invest,2005,ll5(10):2679-2688.
[8]Meijer A J,Codogno P.Regulation and role of autoph-agy in mammalian cells[J].Int J Biochem Cell Biol,2004,36(12):2445-2462.
[9]Mizushima N,Levine B,Cuervo A M,et al.Autophagyfights disease through cellular self digestion[J].Nature,2008,451(7182):1069-1075.
[10]Dreux M,Chisair F V.Viruses and the autophagy ma-chinery[J].Cell Cycle,2010,1295-1307.
[11]Klionsky D J,Cuervo A M,Seglen P O.Methods formonitoring autophagy from yeast to human[J].Auto-phagy,2007,3(3):181-206.
[12]Lockshin R A.Apoptosis,autophagy,and more[J].IntJ Biochem Cell Biol,2004,36(12):2405-2419.
[13]Klionsky D J,Abeliovich H,Agostinis P,et al.Guidelines for the use and interp retation of assays for-monitoring autophagy in higher eukaryotes[J].Auto-phagy,2008,4(2):151-175.
[14]Kundu M,Thompson C B.Autophagy:basic princi-ples and relevance to disease[J].Annu Rev Pathol,2008,3:427-455.
[15]Suzuki K,Ohsumi Y.Molecular machinery of autopha-gosome formation in yeast,Saccharomyces cerevisiae[J].FEBS Lett,2007,581(11):2156-2161.
[16]Nair U,Klionsky D J.Molecular mechanisms andregulation of specific and nonspecific autophagy path-ways inyeast[J].J Biol Chem,2005,280:41785-41788.
[17]Yorimitsu T,Klionsky D J.Autophagy:molecularmachinery for self-eating[J].Cell Death Differ,2005,2:1542-1552.
[18]Klionsky D J,Cregg J M,Dunn W A J,et al.Aunified nomenclature for yeast autophagy related genes[J].Dev Cell,2003,5:539-545.
[19]Mizushima N.In vivo analysis of autophagy inresponse to nutrient starvation using transgenic miceexpressing a fluorescent autophagosome marker[J].Mol Biol Cell,2004,15(3):1101-1111.
[20]Mercer C A.A novel,Human Atg13binding protein,Atg1-01,interacts with ULK1 and is essential formacroautophagy[J].Autophagy,2009,5(5):649-662.
[21]Rubinsztein D C.Potential therapeutic applications ofautophagy[J].Nat Rev Drug Discov,2007,6(4):304-312.
[22]Itakura E.Atg14and UVRAG:Mutually exclusivesubunits of mammalian Beclin 1-PI3Kcomplexes[J].Autophagy,2009,5(4):534-536.
[23]Sekito T.Atg17recruits Atg9to organize the pre-auto-phagosomal structure[J].Genes Cells,2009,14(5):525-538.
[24]Kamada Y,Funakoshi T,Shintani T,et al.Tormedi-ated induction of autophagy via an Apg1protein kinasecomplex[J].J Cell Biol,2000,150:1507-1513.
[25]Chan E Y,Kir S,Tooze S A.siRNA screening of thekinome identifies ULK1as a multi-domain modulator ofautophagy[J].J Biol Chem,2007,282:25464-25474.
[26]Young A R,Chan E Y,Hu X W,et al.Starvation andULK1-dependent cycling of mammalian Atg9betweenthe TGN and endosomes[J].J Cell Sci,2006,119:3888-3900.
[27]Kihara A,Kabeya Y,Ohsumi Y,et al.Beclin-phos-phatidylinositol 3-kinase complex functions at the trans-Golgi network[J].EMBO Rep,2001,2:330-335.
[28]Tassa A,Roux M P,Attaix D,et al.Class III phos-phoinositide 3-kinase-beclin1 complex mediates theamino acid-dependent regulation of autophagy in C2C12myotubes[J].Biochem J,2003,376:577-586.
[29]Panaretou C,Domin J,Cockcroft S,et al.Character-ization of p150,an adaptor protein for the human phos-phatidylinositol(PtdIns)3-kinase.Substrate presenta-tion by phosphatidylinositol transfer protein to thep150.Ptdins 3-kinase complex[J].J Biol Chem,1997,272:2477-2485.
[30]Ohsumi Y.Molecular dissection of autophagy:twoubiquitin-like systems[J].Nat Rev Mol Cell Biol,2001,2:211-216.
[31]Nakatogawa H,Ichimura Y,Ohsumi Y.Atg8,a ubiq-uitin-like protein required for autophagosome forma-tion,mediates membrane tethering and hemifusion[J].Cell,2007,130:165-178.
[35]Eskelinen E L,Saftig P.Autophagy:a lysosomaldegradation pathway with a centr-al role in health anddisease[J].Biochim Biophys Acta,2009,1793(4):664-673.
[32]Talloczy Z,Jiang W,Virgin H W.Regulation ofstarvation and virus induced autophagy by the eIF2alpha kinase signaling pathway[J].Proc Nat.Acad SciUSA,2002,99:190-195.
[33]Orvedahl A,Alexander D,Talloczy Z,et al.HSV-1ICP34.5confers neurovirulence by targeting the Beclin1autophagy protein[J].Cell Host Microbe,2007,1:23-35.
[34]Talloczy Z,Virgin H W.PKR dependent autophagicdegradation of herpes simplex virus type1[J].Autoph-agy,2006,2:24-29.
[35]Alexander D E,Ward S L,Mizushima N,et al.Anal-ysis of the role of autophagy in replication of herpessimplex virus in cell culture[J].J Virol,2007,81:12128-12134.
[36]Lee J S,Li Q,Lee J Y,et al.FLIP-mediated autoph-agy regulation in cell death control[J].Nat Cell Biol,2009,11:1355-1362.
[37]Lee D Y,Sugden B.The LMP1oncogene of EBV acti-vates PERK and the unfolded protein response to driveits own synthesis[J].Blood,2008b,111:2280-2289.
[38]Zhou X,Munger K.Expression of the human papillo-mavirus type 16E7oncoprotein induces an autophagyrelated process and sensitizes normal human keratino-cytes to cell death in response to growth factor depriva-tion[J].Virology,2009,385:192-197.
[39]Kumar S H,Rangarajan A.Simian virus 40small Tantigen activates AMPK and triggers autophagy toprotect cancer cells from nutrient deprivation[J].JVirol,2009,83:8565-8574.
[40]Nakashima A,Tanaka N,Tamai K,et al.Survival ofparvovirus B19infected cells by cellular autophagy[J].Virology,2006,349:254-263.
[41]Sir D,Tian Y,Chen W,et al.The early autophagicpathway is activated by Hepatitis B virus and requiredfor viral DNA replication[J].Proc Natl Acad SciUSA,2010,107(9):4383-4388.
[42]Tang H,Da L,Mao Y,et al.Hepatitis B virus Xprotein sensitizes cells to starvation induced autophagyvia upregulation of beclin 1expression[J].Hepatology,2009,49:60-71.
[43]Jackson W T,Giddings T H,Taylor J r,et al.Sub-version of cellular autophagosomal machinery by RNAviruses[J/OL].PLoS Biol,2005,3:e156.
[44]Suhy D A,Giddings T H,Kirkegaard K.Remodelingthe endoplasmic reticulum by poliovirus infection andby individual viral proteins:an autophagy like originfor virusinduced vesicles[J].J Virol,2000,74:8953-8965.
[45]Taylor M P,Burgon T B,Kirkegaard K,et al.Role ofmicrotubules in extracellular release of poliovirus[J].JVirol,2009,83:6599-6609.
[46]Yoon S Y,Ha Y E,Choi J E,et al.Coxsackievirus B4uses autophagy for replication after calpain activation inrat primary neurons[J].J Virol,2008,82:11976-11978.
[47]Wong J,Zhang J,Si X,et al.Autophagosome sup-ports coxsackievirus B3replication in host cells[J].JVirol,2008,82:9143-9153.
[48]Ait-Goughoulte M,Kanda T,Meyer K,et al.Hepati-tis C virus genotype 1agrowth and induction of autoph-agy[J].J Virol,2008,82:2241-2249.
[49]Sir D,Chen W L,Choi J,et al.Induction of incom-plete autophagic response by hepatitis C virus via theunfolded protein response[J].Hepatology,2008a,48:1054-1061.
[50]Sir D,Liang C,Chen W L,et al.Perturbation of au-tophagic pathway by hepatitis C virus[J].Autophagy,2008b,4:830-831.
[51]Dreux M,Gastaminza P,Wieland S F,et al.Theautophagy machinery is required to initiate hepatitis Cvirus replication[J].Proc Natl Acad Sci USA,2009,106:14046-14051.
[52]Tanida I,Fukasawa M,Ueno T,et al.Knockdown ofautophagy-related gene decreases the production ofinfectious hepatitis C virus particles[J].Autophagy,2009,5:937-945.
[53]Panyasrivanit M,Khakpoor A,Wikan N,et al.Co-lo-calization of constituents of the dengue virus translationand replication machinery with amphisomes[J].J GenVirol,2009,90:448-456.
[54]Khakpoor A,Panyasrivanit M,Wikan N,et al.A rolefor autophagolysosomes in dengue virus 3production inHepG2cells[J].J Gen Virol,2009,90:1093-1103.
[55]Prentice E,Jerome W G,Yoshimori T,et al.Corona-virus replication complex formation utilizes componentsof cellular autophagy[J].J Biol Chem,2004,279:10136-10141.
[56]Zhao Z,Thackray L B,Miller B C,et al.Coronavirusreplication does not require the autophagy gene ATG5[J].Autophagy,2007,3:581-585.
[57]Gannage M,Dormann D,Albrecht R,et al.Matrixprotein 2of influenza A virus blocks autophagosomefusion with lysosomes[J].Cell Host Microbe,2009,6:367-380.
[58]Zhou X,Spangle J M,Munger K.Expression of aviral oncoprotein in normal human epithelial cells trig-gers an autophagy related process:is autophagy an“A-chilles’heel”of human cancers?[J]Autophagy,2009a,5(4):578-579.
[59]Shelly S,Lukinova N,Bambina S,et al.Autophagy isan essential component of Drosophila immunity againstvesicular stomatitis virus[J].Immunity,2009,30:588-598.
[60]Berkova Z,Crawford S E,Trugnan G,et al,RotavirusNSP4induces a novel vesicular compartment regulatedby calcium and associated with viroplasms[J].J Virol,2006,80:6061-6071.
[61]Espert L,Varbanov M,Robert-Hebmann V,et al.Differential role of autophagy in CD4Tcells and mac-rophages during X4and R5 HIV-1infection[J/OL].PLoS One,2009,4:e5787.
[62]Kyei G B,Dinkins C,Davis A S,et al.Autophagypathway intersects with HIV-1biosynthesis and regu-lates viral yields in macrophages[J].J Cell Biol,2009,186:255-268.
[63]Zhou D,Spector S A.Human immunodeficiency virustype-1infection inhibits autophagy[J].AIDS,2008,22:695-699.
[64]Brass A L,Dykxhoorn D M,Benita Y,et al.Identifi-cation of host proteins required for HIV infectionthrough a functional genomic screen[J].Science,2008,319:921-926.
基本信息:
DOI：10.13242/j.cnki.bingduxuebao.002355
中图分类号:R363
引用信息:
[1]陶冶,任晓峰.细胞自噬与病毒感染[J].病毒学报,2013,29(01):76-84.DOI:10.13242/j.cnki.bingduxuebao.002355.
基金信息:
教育部新世纪优秀人才项目(NCET-10-0144);; 教育部科技研究重点项目(212038);; 黑龙江省普通高等学校长江学者后备支持计划;; 哈尔滨市科技创新人才研究专项资金(RC2012XK002003)
2013-01-31
2013-01-31
2013-01-31