Autophagy and the immune system

Annual Review of Immunology

Volumn 30, Issue , 2012, Pages 611-646

  Kuballa, Petric ^a,b   Nolte, Whitney M ^a,b   Castoreno, Adam B ^a,b   Xavier, Ramnik J ^a,b  

^a HARVARD UNIVERSITY   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

Adaptive immunity; Bacterial infection; Innate immunity; Macroautophagy; Virus; Xenophagy

Indexed keywords

BACTERIAL ANTIGEN; HISTONE DEACETYLASE 6; INTERLEUKIN 18; INTERLEUKIN 1BETA; MITOCHONDRIAL DNA; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 PHOSPHATE;

ACETYLATION; APOPTOSIS; AUTOPHAGOSOME; BIOGENESIS; CAENORHABDITIS ELEGANS; CELL MEMBRANE; DEGRADATION; ENDOCYTOSIS; ENDOPLASMIC RETICULUM; FIBROBLAST; GENETIC TRANSCRIPTION; HUMAN; IMMUNE SYSTEM; IMMUNITY; INFLAMMATION; INNATE IMMUNITY; LYSOSOME; MACROAUTOPHAGY; MICROAUTOPHAGY; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN PROCESSING; REGULATORY MECHANISM; REVIEW; SACCHAROMYCES CEREVISIAE; SIGNAL TRANSDUCTION; UBIQUITINATION;

ADAPTIVE IMMUNITY; ANIMALS; AUTOPHAGY; HUMANS; IMMUNE SYSTEM; IMMUNITY, INNATE; INFECTION;

EID: 84859386792     PISSN: 07320582     EISSN: 15453278     Source Type: Book Series    
DOI: 10.1146/annurev-immunol-020711-074948     Document Type: Review

References (221)

1. Yang Z, Klionsky DJ. 2010. Eaten alive: a history of macroautophagy. Nat. Cell Biol. 12:814-22
2. Kouroku Y, Fujita E, Tanida I, Ueno T, Isoai A, et al. 2007. ER stress (PERK/eIF2α phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation. Cell Death Differ. 14:230-39
3. Jain A, Lamark T, Sjottem E, Larsen KB, Awuh JA, et al. 2010. p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response elementdriven gene transcription. J. Biol. Chem. 285:22576-91
4. Shin DM, Jeon BY, Lee HM, Jin HS, Yuk JM, et al. 2010. Mycobacterium tuberculosis Eis regulates autophagy, inflammation, and cell death through redox-dependent signaling. PLo S Pathog. 6:e1001230
5. TalMC, SasaiM, LeeHK, Yordy B, ShadelGS, IwasakiA. 2009. Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling. Proc. Natl. Acad. Sci. USA 106:2770-75
6. Lee HK, Lund JM, Ramanathan B, Mizushima N, Iwasaki A. 2007. Autophagy-dependent viral recognition by plasmacytoid dendritic cells. Science 315:1398-401
7. Franchi L, Eigenbrod T, Munoz-Planillo R, NunezG. 2009. The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nat. Immunol. 10:241-47
8. Nakahira K, Haspel JA, Rathinam VA, Lee SJ, Dolinay T, et al. 2011. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat. Immunol. 12:222-30
9. Lauber K, Blumenthal SG, Waibel M, Wesselborg S. 2004. Clearance of apoptotic cells: getting rid of the corpses. Mol. Cell 14:277-87
10. Qu X, Zou Z, Sun Q, Luby-Phelps K, Cheng P, et al. 2007. Autophagy gene-dependent clearance of apoptotic cells during embryonic development. Cell 128:931-46
11. JiaW, He YW. 2011. Temporal regulation of intracellular organelle homeostasis in T lymphocytes by autophagy. J. Immunol. 186:5313-22
12. Jia W, Pua HH, Li QJ, He YW. 2011. Autophagy regulates endoplasmic reticulum homeostasis and calcium mobilization in T lymphocytes. J. Immunol. 186:1564-74
13. Miller BC, Zhao Z, Stephenson LM, Cadwell K, PuaHH, et al. 2008. The autophagy gene ATG5 plays an essential role in B lymphocyte development. Autophagy 4:309-14
14. Nedjic J, Aichinger M, Emmerich J, Mizushima N, Klein L. 2008. Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance. Nature 455:396-400
15. Lee HK, Mattei LM, Steinberg BE, Alberts P, Lee YH, et al. 2010. In vivo requirement for Atg5 in antigen presentation by dendritic cells. Immunity 32:227-39
16. Martens S, Parvanova I, Zerrahn J, Griffiths G, Schell G, et al. 2005. Disruption of Toxoplasma gondii parasitophorous vacuoles by the mouse p47-resistance GTPases. PLo S Pathog. 1:e24
17. Zhao Z, Fux B, Goodwin M, Dunay IR, Strong D, et al. 2008. Autophagosome-independent essential function for the autophagy protein Atg5 in cellular immunity to intracellular pathogens. Cell Host Microbe 4:458-69
18. Levine B, MizushimaN, VirginHW. 2011. Autophagy in immunity and inflammation. Nature 469:323-35
19. MizushimaN, Yoshimori T, Levine B. 2010. Methods in mammalian autophagy research. Cell 140:313-26
20. Yu L, McPhee CK, Zheng L, Mardones GA, Rong Y, et al. 2010. Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature 465:942-46
21. Tooze SA, Yoshimori T. 2010. The origin of the autophagosomal membrane. Nat. Cell Biol. 12:831-35
22. TsukadaM, Ohsumi Y. 1993. Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett. 333:169-74
23. Mercer CA, Kaliappan A, Dennis PB. 2009. A novel, human Atg13 binding protein, Atg101, interacts with ULK1 and is essential for macroautophagy. Autophagy 5:649-62
24. Hara T, Takamura A, Kishi C, Iemura S, Natsume T, et al. 2008. FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells. J. Cell Biol. 181:497-510
25. Jung CH, Jun CB, Ro SH, Kim YM, Otto NM, et al. 2009. ULK-Atg13-FIP200 complexes mediate m TOR signaling to the autophagy machinery. Mol. Biol. Cell 20:1992-2003
26. Kamada Y, Yoshino K, Kondo C, Kawamata T, Oshiro N, et al. 2010. Tor directly controls the Atg1 kinase complex to regulate autophagy. Mol. Cell. Biol. 30:1049-58
27. Cheong H, Nair U, Geng J, Klionsky DJ. 2008. The Atg1 kinase complex is involved in the regulation of protein recruitment to initiate sequestering vesicle formation for nonspecific autophagy in Saccharomyces cerevisiae. Mol. Biol. Cell 19:668-81
28. Chan EY, Longatti A, McKnight NC, Tooze SA. 2009. Kinase-inactivated ULK proteins inhibit autophagy via their conserved C-terminal domains using an Atg13-independent mechanism. Mol. Cell. Biol. 29:157-71
29. Weidberg H, Shvets E, Elazar Z. 2011. Biogenesis and cargo selectivity of autophagosomes. Annu. Rev. Biochem. 80:125-56
30. Kageyama S, Omori H, Saitoh T, Sone T, Guan JL, et al. 2011. The LC3 recruitment mechanism is separate from Atg9L1-dependent membrane formation in the autophagic response against Salmonella. Mol. Biol. Cell. 22:2290-300
31. Mari M, Griffith J, Rieter E, Krishnappa L, Klionsky DJ, Reggiori F. 2010. An Atg9-containing compartment that functions in the early steps of autophagosome biogenesis. J. Cell Biol. 190:1005-22
32. Kihara A, Noda T, Ishihara N, Ohsumi Y. 2001. Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae. J. Cell Biol. 152:519-30
33. Itakura E, Kishi C, Inoue K, Mizushima N. 2008. Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG. Mol. Biol. Cell 19:5360-72
34. Matsunaga K, Saitoh T, Tabata K, Omori H, Satoh T, et al. 2009. Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages. Nat. Cell Biol. 11:385-96
35. Zhong Y, Wang QJ, Li X, Yan Y, Backer JM, et al. 2009. Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex. Nat. Cell Biol. 11:468-76
36. Sun Q, Fan W, Chen K, Ding X, Chen S, Zhong Q. 2008. Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III phosphatidylinositol 3-kinase. Proc. Natl. Acad. Sci. USA 105:19211-16
37. Matsunaga K, Morita E, Saitoh T, Akira S, Ktistakis NT, et al. 2010. Autophagy requires endoplasmic reticulum targeting of the PI3-kinase complex via Atg14L. J. Cell Biol. 190:511-21
38. Takahashi Y, Coppola D, Matsushita N, Cualing HD, SunM, et al. 2007. Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. Nat. Cell Biol. 9:1142-51
39. Liang C, Feng P, Ku B, Dotan I, Canaani D, et al. 2006. Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG. Nat. Cell Biol. 8:688-99
40. Liang C, Lee JS, Inn KS, Gack MU, Li Q, et al. 2008. Beclin1-binding UVRAG targets the class C Vps complex to coordinate autophagosome maturation and endocytic trafficking. Nat. Cell Biol. 10:776-87
41. Proikas-Cezanne T, Waddell S, Gaugel A, Frickey T, Lupas A, Nordheim A. 2004. WIPI-1α(WIPI49), a member of the novel 7-bladed WIPI protein family, is aberrantly expressed in human cancer and is linked to starvation-induced autophagy. Oncogene 23:9314-25
42. Polson HE, de Lartigue J, Rigden DJ, ReedijkM, Urbe S, et al. 2010. Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phagophores and positively regulates LC3 lipidation. Autophagy 6:506-22
43. ObaraK, SekitoT, NiimiK, OhsumiY. 2008. TheAtg18-Atg2 complex is recruited to autophagic membranes via phosphatidylinositol 3-phosphate and exerts an essential function. J. Biol. Chem. 283:23972-80
44. Behrends C, Sowa ME, Gygi SP, Harper JW. 2010. Network organization of the human autophagy system. Nature 466:68-76
45. Axe EL, Walker SA, ManifavaM, Chandra P, Roderick HL, et al. 2008. Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. J. Cell Biol. 182:685-701
46. Simonsen A, Birkeland HC, Gillooly DJ, Mizushima N, Kuma A, et al. 2004. Alfy, a novel FYVEdomain-containing protein associated with protein granules and autophagic membranes. J. Cell Sci. 117:4239-51
47. Clausen TH, Lamark T, Isakson P, Finley K, Larsen KB, et al. 2010. p62/SQSTM1 and ALFY interact to facilitate the formation of p62 bodies/ALIS and their degradation by autophagy. Autophagy 6:330-44
48. Filimonenko M, Isakson P, Finley KD, Anderson M, Jeong H, et al. 2010. The selective macroautophagic degradation of aggregated proteins requires the PI3P-binding protein Alfy. Mol. Cell 38:265-79
49. Mizushima N, Noda T, Yoshimori T, Tanaka Y, Ishii T, et al. 1998. A protein conjugation system essential for autophagy. Nature 395:395-98
50. Mizushima N, Sugita H, Yoshimori T, Ohsumi Y. 1998. A new protein conjugation system in human. The counterpart of the yeast Apg12p conjugation system essential for autophagy. J. Biol. Chem. 273:33889-92
51. Fujita N, Saitoh T, Kageyama S, Akira S, Noda T, Yoshimori T. 2009. Differential involvement of Atg16L1 in Crohn disease and canonical autophagy: analysis of the organization of the Atg16L1 complex in fibroblasts. J. Biol. Chem. 284:32602-9
52. Mizushima N, Kuma A, Kobayashi Y, Yamamoto A, Matsubae M, et al. 2003. Mouse Apg16L, a novel WD-repeat protein, targets to the autophagic isolation membrane with the Apg12-Apg5 conjugate. J. Cell Sci. 116:1679-88
53. Zheng H, Ji C, Li J, Jiang H, Ren M, et al. 2004. Cloning and analysis of human Apg16L. DNA Seq. 15:303-5
54. Hanada T, Noda NN, Satomi Y, Ichimura Y, Fujioka Y, et al. 2007. The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy. J. Biol. Chem. 282:37298-302
55. Radoshevich L, Murrow L, Chen N, Fernandez E, Roy S, et al. 2010. ATG12 conjugation to ATG3 regulates mitochondrial homeostasis and cell death. Cell 142:590-600
56. Yousefi S, Perozzo R, Schmid I, Ziemiecki A, Schaffner T, et al. 2006. Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat. Cell Biol. 8:1124-32
57. Russo R, Berliocchi L, Adornetto A, Varano GP, Cavaliere F, et al. 2011. Calpain-mediated cleavage of Beclin-1 and autophagy deregulation following retinal ischemic injury in vivo. Cell Death Dis. 2:e144
58. Wirawan E, Vande Walle L, Kersse K, Cornelis S, Claerhout S, et al. 2010. Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria. Cell Death Dis. 1:e18
59. Rohn TT, Wirawan E, Brown RJ, Harris JR, Masliah E, Vandenabeele P. 2011. Depletion of Beclin-1 due to proteolytic cleavage by caspases in the Alzheimer's disease brain. Neurobiol. Dis. 43:68-78
60. BetinVM, Lane JD. 2009. Caspase cleavage of Atg4D stimulates GABARAP-L1 processing and triggers mitochondrial targeting and apoptosis. J. Cell Sci. 122:2554-66
61. Norman JM, Cohen GM, Bampton ET. 2010. The in vitro cleavage of the hAtg proteins by cell death proteases. Autophagy 6:1042-56
62. Kabeya Y, MizushimaN, UenoT, Yamamoto A, KirisakoT, et al. 2000. LC3, amammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 19:5720-28
63. Kabeya Y, Mizushima N, Yamamoto A, Oshitani-Okamoto S, Ohsumi Y, Yoshimori T. 2004. LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation. J. Cell Sci. 117:2805-12
64. SatooK, Noda NN, Kumeta H, Fujioka Y, MizushimaN, et al. 2009. The structure of Atg4B-LC3 complex reveals themechanism of LC3 processing and delipidation during autophagy. EMBO J. 28:1341-50
65. Li M, Hou Y, Wang J, Chen X, Shao ZM, Yin XM. 2011. Kinetics comparisons of mammalian Atg4 homologues indicate selective preferences toward diverse Atg8 substrates. J. Biol. Chem. 286:7327-38
66. Weidberg H, Shvets E, Shpilka T, Shimron F, Shinder V, Elazar Z. 2010. LC3 and GATE-16/GABARAP subfamilies are both essential yet act differently in autophagosome biogenesis. EMBO J. 29:1792-802
67. Noda NN, Ohsumi Y, Inagaki F. 2010. Atg8-family interacting motif crucial for selective autophagy. FEBS Lett. 584:1379-85
68. Xie Z, Nair U, Klionsky DJ. 2008. Atg8 controls phagophore expansion during autophagosome formation. Mol. Biol. Cell 19:3290-98
69. Furuya N, Yu J, Byfield M, Pattingre S, Levine B. 2005. The evolutionarily conserved domain of Beclin 1 is required for Vps34 binding, autophagy and tumor suppressor function. Autophagy 1:46-52
70. Liang XH, Kleeman LK, Jiang HH, Gordon G, Goldman JE, et al. 1998. Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein. J. Virol. 72:8586-96
71. Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, et al. 1999. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402:672-76
72. Zalckvar E, Berissi H, Mizrachy L, Idelchuk Y, Koren I, et al. 2009. DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl-XL and induction of autophagy. EMBO Rep. 10:285-92
73. Wei Y, Pattingre S, Sinha S, Bassik M, Levine B. 2008. JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol. Cell 30:678-88
74. Taguchi-Atarashi N, Hamasaki M, Matsunaga K, Omori H, Ktistakis NT, et al. 2010. Modulation of local PtdIns3P levels by the PI phosphataseMTMR3 regulates constitutive autophagy. Traffic 11:468-78
75. Vergne I, Roberts E, Elmaoued RA, Tosch V, Delgado MA, et al. 2009. Control of autophagy initiation by phosphoinositide 3-phosphatase jumpy. EMBO J. 28:2244-58
76. Cherra SJ 3rd, Kulich SM, Uechi G, Balasubramani M, Mountzouris J, et al. 2010. Regulation of the autophagy protein LC3 by phosphorylation. J. Cell Biol. 190:533-39
77. Weidberg H, Shpilka T, Shvets E, Abada A, Shimron F, Elazar Z. 2011. LC3 and GATE-16 N termini mediate membrane fusion processes required for autophagosome biogenesis. Dev. Cell 20:444-54
78. JiangH, Cheng D, LiuW, Peng J, Feng J. 2010. Protein kinaseCinhibits autophagy and phosphorylates LC3. Biochem. Biophys. Res. Commun. 395:471-76
79. Szyniarowski P, Corcelle-Termeau E, Farkas T, Hoyer-Hansen M, Nylandsted J, et al. 2011. A comprehensive si RNA screen for kinases that suppress macroautophagy in optimal growth conditions. Autophagy 7:892-903
80. Lipinski MM, Hoffman G, Ng A, Zhou W, Py BF, et al. 2010. A genome-wide si RNA screen reveals multiple mTORC1 independent signaling pathways regulating autophagy under normal nutritional conditions. Dev. Cell 18:1041-52
81. Morselli E, Marino G, Bennetzen MV, Eisenberg T, Megalou E, et al. 2011. Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome. J. Cell Biol. 192:615-29
82. Lee IH, Finkel T. 2009. Regulation of autophagy by the p300 acetyltransferase. J. Biol. Chem. 284:6322-28
83. Lee IH, Cao L, Mostoslavsky R, Lombard DB, Liu J, et al. 2008. A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc. Natl. Acad. Sci. USA 105:3374-79
84. Lee JY, Nagano Y, Taylor JP, Lim KL, Yao TP. 2010. Disease-causing mutations in Parkin impair mitochondrial ubiquitination, aggregation, andHDAC6-dependentmitophagy. J. Cell Biol. 189:671-79
85. Lee JY, Koga H, Kawaguchi Y, Tang W, Wong E, et al. 2010. HDAC6 controls autophagosome maturation essential for ubiquitin-selective quality-control autophagy. EMBO J. 29:969-80
86. IwataA, RileyBE, Johnston JA, Kopito RR. 2005. HDAC6and microtubules are required for autophagic degradation of aggregated huntingtin. J. Biol. Chem. 280:40282-92
87. Jeong H, Then F, Melia TJ Jr, Mazzulli JR, Cui L, et al. 2009. Acetylation targets mutant huntingtin to autophagosomes for degradation. Cell 137:60-72
88. Mookerjee S, Papanikolaou T, Guyenet SJ, Sampath V, Lin A, et al. 2009. Post-translational modification of ataxin-7 at lysine 257 prevents autophagy-mediated turnover of an N-terminal caspase-7 cleavage fragment. J. Neurosci. 29:15134-44
89. Gamerdinger M, Hajieva P, Kaya AM, Wolfrum U, Hartl FU, Behl C. 2009. Protein quality control during aging involves recruitment of the macroautophagy pathway by BAG3. EMBO J. 28:889-901
90. Kraft C, Peter M, Hofmann K. 2010. Selective autophagy: ubiquitin-mediated recognition and beyond. Nat. Cell Biol. 12:836-41
91. Cemma M, Kim PK, Brumell JH. 2011. The ubiquitin-binding adaptor proteins p62/SQSTM1 and NDP52 are recruited independently to bacteria-associated microdomains to target Salmonella to the autophagy pathway. Autophagy 7:341-45
92. Mostowy S, Sancho-Shimizu V, Hamon M, Simeone R, Brosch R, et al. 2011. p62 and NDP52 target intracytosolic Shigella and Listeria to different autophagy pathways. J. Biol. Chem. 286:26987-95
93. Hampe J, Franke A, Rosenstiel P, Till A, Teuber M, et al. 2007. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat. Genet. 39:207-11
94. Rioux JD, Xavier RJ, TaylorKD, Silverberg MS, Goyette P, et al. 2007. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat. Genet. 39:596-604
95. Saitoh T, Fujita N, Jang MH, Uematsu S, Yang BG, et al. 2008. Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1βproduction. Nature 456:264-68
96. Zhou R, Yazdi AS, Menu P, Tschopp J. 2011. A role for mitochondria in NLRP3 inflammasome activation. Nature 469:221-25
97. Harris J, Hartman M, Roche C, Zeng SG, O'Shea A, et al. 2011. Autophagy controls IL-1βsecretion by targeting pro-IL-1βfor degradation. J. Biol. Chem. 286:9587-97
98. Plantinga TS, Crisan TO, Oosting M, van de Veerdonk FL, de Jong DJ, et al. 2011. Crohn's diseaseassociated ATG16L1 polymorphism modulates pro-inflammatory cytokine responses selectively upon activation of NOD2. Gut 60:1229-35
99. Travassos LH, Carneiro LA, Ramjeet M, Hussey S, Kim YG, et al. 2010. Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry. Nat. Immunol. 11:55-62
100. Cooney R, Baker J, Brain O, Danis B, Pichulik T, et al. 2010. NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat. Med. 16:90-97
101. Kuballa P, Huett A, Rioux JD, Daly MJ, Xavier RJ. 2008. Impaired autophagy of an intracellular pathogen induced by a Crohn's disease associated ATG16L1 variant. PLo S ONE 3:e3391
102. Lapaquette P, Glasser AL, Huett A, Xavier RJ, Darfeuille-Michaud A. 2010. Crohn's disease-associated adherent-invasive E. coli are selectively favoured by impaired autophagy to replicate intracellularly. Cell Microbiol. 12:99-113
103. CadwellK, Liu JY, Brown SL, MiyoshiH, Loh J, et al. 2008. A key role for autophagy and the autophagy gene Atg16L1 in mouse and human intestinal Paneth cells. Nature 456:259-263
104. Cadwell K, Patel KK, Maloney NS, Liu TC, Ng AC, et al. 2010. Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine. Cell 141:1135-45
105. Bekpen C, Marques-BonetT, Alkan C, Antonacci F, Leogrande MB, et al. 2009. Death and resurrection of the human IRGM gene. PLo S Genet. 5:e1000403
106. Bekpen C, Xavier RJ, Eichler EE. 2010. Human IRGM gene "to be or not to be. " Semin. Immunopathol. 32:437-44
107. Parkes M, Barrett JC, Prescott NJ, Tremelling M, Anderson CA, et al. 2007. Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. Nat. Genet. 39:830-32
108. McCarroll SA, Huett A, Kuballa P, Chilewski SD, Landry A, et al. 2008. Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease. Nat. Genet. 40:1107-12
109. Brest P, Lapaquette P, Souidi M, Lebrigand K, Cesaro A, et al. 2011. A synonymous variant in IRGM alters a binding site for miR-196 and causes deregulation of IRGM-dependent xenophagy in Crohn's disease. Nat. Genet. 43:242-45
110. Singh SB, Davis AS, Taylor GA, Deretic V. 2006. Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science 313:1438-41
111. Zhao YO, Konen-Waisman S, Taylor GA, Martens S, Howard JC. 2010. Localisation and mislocalisation of the interferon-inducible immunity-related GTPase, Irgm1 (LRG-47) in mouse cells. PLo S ONE 5:e8648
112. Singh SB, Ornatowski W, Vergne I, Naylor J, Delgado M, et al. 2010. Human IRGM regulates autophagy and cell-autonomous immunity functions through mitochondria. Nat. Cell Biol. 12:1154-65
113. Komatsu M, Waguri S, Koike M, Sou YS, Ueno T, et al. 2007. Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell 131:1149-63
114. Matsumoto G, Wada K, Okuno M, Kurosawa M, Nukina N. 2011. Serine 403 phosphorylation of p62/SQSTM1 regulates selective autophagic clearance of ubiquitinated proteins. Mol. Cell 44:279-89
115. Duran A, Amanchy R, Linares JF, Joshi J, Abu-Baker S, et al. 2011. p62 is a key regulator of nutrient sensing in the mTORC1 pathway. Mol. Cell 44:134-46
116. Kim JY, Ozato K. 2009. The sequestosome 1/p62 attenuates cytokine gene expression in activated macrophages by inhibiting IFN regulatory factor 8 and TNF receptor-associated factor 6/NF-κB activity. J. Immunol. 182:2131-40
117. Komatsu M, Kurokawa H, Waguri S, Taguchi K, Kobayashi A, et al. 2010. The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat. Cell Biol. 12:213-23
118. Johansen T, Lamark T. 2011. Selective autophagy mediated by autophagic adapter proteins. Autophagy 7:279-96
119. Copple IM, Lister A, Obeng AD, Kitteringham NR, Jenkins RE, et al. 2010. Physical and functional interaction of sequestosome 1 with Keap1 regulates the Keap1-Nrf2 cell defense pathway. J. Biol. Chem. 285:16782-88
120. Fujita K, Maeda D, Xiao Q, Srinivasula SM. 2011. Nrf2-mediated induction of p62 controls Toll-like receptor-4-driven aggresome-like induced structure formation and autophagic degradation. Proc. Natl. Acad. Sci. USA 108:1427-32
121. Jin Z, Li Y, Pitti R, Lawrence D, Pham VC, et al. 2009. Cullin3-based polyubiquitination and p62-dependent aggregation of caspase-8 mediate extrinsic apoptosis signaling. Cell 137:721-35
122. HouW, Han J, Lu C, Goldstein LA, Rabinowich H. 2010. Autophagic degradation of active caspase-8: a crosstalk mechanism between autophagy and apoptosis. Autophagy 6:891-900
123. Oberst A, Green DR. 2011. It cuts both ways: reconciling the dual roles of caspase 8 in cell death and survival. Nat. Rev. Mol. Cell Biol. 12:757-63
124. Gunther C, Martini E, Wittkopf N, Amann K, Weigmann B, et al. 2011. Caspase-8 regulates TNF-α-induced epithelial necroptosis and terminal ileitis. Nature 477:335-39
125. Bell BD, Leverrier S, Weist BM, Newton RH, Arechiga AF, et al. 2008. FADD and caspase-8 control the outcome of autophagic signaling in proliferating T cells. Proc. Natl. Acad. Sci. USA 105:16677-82
126. Patel JC, HuefferK, Lam TT, Galan JE. 2009. Diversification of a Salmonella virulence protein function by ubiquitin-dependent differential localization. Cell 137:283-94
127. Wild P, Farhan H, McEwan DG, Wagner S, Rogov VV, et al. 2011. Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth. Science 333:228-33
128. Shahnazari S, Yen WL, Birmingham CL, Shiu J, Namolovan A, et al. 2010. A diacylglycerol-dependent signaling pathway contributes to regulation of antibacterial autophagy. Cell Host Microbe 8:137-46
129. Shahnazari S, Namolovan A, Mogridge J, Kim PK, Brumell JH. 2011. Bacterial toxins can inhibit host cell autophagy through c AMP generation. Autophagy 7:957-65
130. Kumar D, Nath L, Kamal MA, Varshney A, Jain A, et al. 2010. Genome-wide analysis of the host intracellular network that regulates survival of Mycobacterium tuberculosis. Cell 140:731-43
131. Gutierrez MG, Master SS, Singh SB, Taylor GA, Colombo MI, Deretic V. 2004. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119:753-66
132. Armstrong JA, Hart PD. 1971. Response of cultured macrophages to Mycobacterium tuberculosis, with observations on fusion of lysosomes with phagosomes. J. Exp. Med. 134:713-40
133. PonpuakM, Davis AS, Roberts EA, DelgadoMA, Dinkins C, et al. 2010. Delivery of cytosolic components by autophagic adaptor protein p62 endows autophagosomes with unique antimicrobial properties. Immunity 32:329-41
134. Alonso S, Pethe K, Russell DG, Purdy GE. 2007. Lysosomal killing of Mycobacterium mediated by ubiquitin-derived peptides is enhanced by autophagy. Proc. Natl. Acad. Sci. USA 104:6031-36
135. Kim BH, Shenoy AR, Kumar P, Das R, Tiwari S, MacMicking JD. 2011. A family of IFN-γ-inducible 65-k D GTPases protects against bacterial infection. Science 332:717-21
136. Deckert-Schluter M, Bluethmann H, Rang A, Hof H, Schluter D. 1998. Crucial role of TNF receptor type 1 (p55), but not of TNF receptor type 2 (p75), in murine toxoplasmosis. J. Immunol. 160:3427-36
137. Scharton-Kersten TM, Yap G, Magram J, Sher A. 1997. Inducible nitric oxide is essential for host control of persistent but not acute infection with the intracellular pathogen Toxoplasma gondii. J. Exp. Med. 185:1261-73
138. Suzuki Y, Orellana MA, Schreiber RD, Remington JS. 1988. Interferon-γ: the major mediator of resistance against Toxoplasma gondii. Science 240:516-18
139. Hunn JP, Feng CG, Sher A, Howard JC. 2011. The immunity-related GTPases in mammals: a fastevolving cell-autonomous resistance system against intracellular pathogens. Mamm. Genome 22:43-54
140. Liesenfeld O, Parvanova I, Zerrahn J, Han SJ, Heinrich F, et al. 2011. The IFN-γ-inducible GTPase, Irga6, protects mice against Toxoplasma gondii but not against Plasmodium berghei and some other intracellular pathogens. PLo S ONE 6:e20568
141. Portillo JA, Okenka G, Reed E, Subauste A, Van Grol J, et al. 2010. The CD40-autophagy pathway is needed for host protection despite IFN-γ-dependent immunity and CD40 induces autophagy via control of P21 levels. PLo S ONE 5:e14472
142. Andrade RM, WessendarpM, Gubbels MJ, Striepen B, Subauste CS. 2006. CD40 induces macrophage anti-Toxoplasma gondii activity by triggering autophagy-dependent fusion of pathogen-containing vacuoles and lysosomes. J. Clin. Investig. 116:2366-77
143. Jounai N, Takeshita F, Kobiyama K, Sawano A, Miyawaki A, et al. 2007. The Atg5-Atg12 conjugate associates with innate antiviral immune responses. Proc. Natl. Acad. Sci. USA 104:14050-55
144. Joubert PE, Meiffren G, Gregoire IP, Pontini G, Richetta C, et al. 2009. Autophagy induction by the pathogen receptor CD46. Cell Host Microbe 6:354-66
145. Talloczy Z, JiangW, Virgin HW4th, Leib DA, Scheuner D, et al. 2002. Regulation of starvation-and virus-induced autophagy by the eIF2αkinase signaling pathway. Proc. Natl. Acad. Sci. USA 99:190-95
146. Orvedahl A, MacPherson S, Sumpter R Jr, Talloczy Z, Zou Z, Levine B. 2010. Autophagy protects against Sindbis virus infection of the central nervous system. Cell Host Microbe 7:115-27
147. Sumpter R Jr, Levine B. 2011. Selective autophagy and viruses. Autophagy 7:260-65
148. Lee JS, Li Q, Lee JY, Lee SH, Jeong JH, et al. 2009. FLIP-mediated autophagy regulation in cell death control. Nat. Cell Biol. 11:1355-62
149. OrvedahlA, AlexanderD, Talloczy Z, SunQ, Wei Y, et al. 2007. HSV-1ICP34. 5 confers neurovirulence by targeting the Beclin 1 autophagy protein. Cell Host Microbe 1:23-35
150. Pattingre S, Tassa A, Qu X, Garuti R, Liang XH, et al. 2005. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122:927-39
151. Talloczy Z, Virgin HWt, Levine B. 2006. PKR-dependent autophagic degradation of herpes simplex virus type 1. Autophagy 2:24-29
152. He B, Gross M, Roizman B. 1997. The γ(1)34. 5 protein of herpes simplex virus 1 complexes with protein phosphatase 1αto dephosphorylate the αsubunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase. Proc. Natl. Acad. Sci. USA 94:843-48
153. Li Y, Zhang C, Chen X, Yu J, Wang Y, et al. 2011. ICP34. 5 protein of herpes simplex virus facilitates the initiation of protein translation by bridging eukaryotic initiation factor 2α (eIF2α) and protein phosphatase 1. J. Biol. Chem. 286:24785-92
154. + T-cell responses. J. Virol. 83:12164-71
155. Blanchet FP, Moris A, Nikolic DS, Lehmann M, Cardinaud S, et al. 2010. Human immunodeficiency virus-1 inhibition of immunoamphisomes in dendritic cells impairs early innate and adaptive immune responses. Immunity 32:654-69
156. Kyei GB, Dinkins C, Davis AS, Roberts E, Singh SB, et al. 2009. Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages. J. Cell Biol. 186:255-68
157. Harman AN, Kraus M, Bye CR, Byth K, Turville SG, et al. 2009. HIV-1-infected dendritic cells show 2 phases of gene expression changes, with lysosomal enzyme activity decreased during the second phase. Blood 114:85-94
158. Campbell GR, Spector SA. 2011. Hormonally active vitamin D3 (1α, 25-dihydroxycholecalciferol) triggers autophagy in human macrophages that inhibits HIV-1 infection. J. Biol. Chem. 286:18890-902
159. Espert L, Denizot M, Grimaldi M, Robert-Hebmann V, Gay B, et al. 2006. Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to CXCR4. J. Clin. Investig. 116:2161-72
160. DenizotM, VarbanovM, Espert L, Robert-Hebmann V, Sagnier S, et al. 2008. HIV-1 gp41 fusogenic function triggers autophagy in uninfected cells. Autophagy 4:998-1008
161. Zhou D, Spector SA. 2008. Human immunodeficiency virus type-1 infection inhibits autophagy. AIDS 22(6):695-99
162. Lenz HD, Haller E, Melzer E, Kober K, Wurster K, et al. 2011. Autophagy differentially controls plant basal immunity to biotrophic and necrotrophic pathogens. Plant J. 66:818-30
163. Qin QM, Luo J, Lin X, Pei J, Li L, et al. 2011. Functional analysis of host factors that mediate the intracellular lifestyle of Cryptococcus neoformans. PLo S Pathog. 7:e1002078
164. Dengjel J, Schoor O, Fischer R, Reich M, Kraus M, et al. 2005. Autophagy promotes MHC class II presentation of peptides from intracellular source proteins. Proc. Natl. Acad. Sci. USA 102:7922-27
165. KasaiM, Tanida I, Ueno T, Kominami E, Seki S, et al. 2009. Autophagic compartments gain access to the MHC class II compartments in thymic epithelium. J. Immunol. 183:7278-85
166. Schmid D, Pypaert M, Munz C. 2007. Antigen-loading compartments for major histocompatibility complex class II molecules continuously receive input from autophagosomes. Immunity 26:79-92
167. Jagannath C, Lindsey DR, Dhandayuthapani S, Xu Y, Hunter RLJr, Eissa NT. 2009. Autophagy enhances the efficacy of BCG vaccine by increasing peptide presentation in mouse dendritic cells. Nat. Med. 15:267-76
168. English L, Chemali M, Duron J, Rondeau C, Laplante A, et al. 2009. Autophagy enhances the presentation of endogenous viral antigens on MHC class I molecules during HSV-1 infection. Nat. Immunol. 10:480-87
169. + T cells. Cell Death Differ. 16:991-1005
170. Remijsen Q, Vanden Berghe T, Wirawan E, Asselbergh B, Parthoens E, et al. 2011. Neutrophil extracellular trap cell death requires both autophagy and superoxide generation. Cell Res. 21(2):290-304
171. Berger SB, Romero X, Ma C, Wang G, Faubion WA, et al. 2010. SLAM is a microbial sensor that regulates bacterial phagosome functions in macrophages. Nat. Immunol. 11:920-27
172. Deuretzbacher A, Czymmeck N, Reimer R, Trulzsch K, Gaus K, et al. 2009. β1 integrin-dependent engulfment of Yersinia enterocolitica by macrophages is coupled to the activation of autophagy and suppressed by type III protein secretion. J. Immunol. 183:5847-60
173. Mihalache CC, Yousefi S, Conus S, Villiger PM, Schneider EM, Simon HU. 2011. Inflammationassociated autophagy-related programmed necrotic death of human neutrophils characterized by organelle fusion events. J. Immunol. 186:6532-42
174. Mitroulis I, Kourtzelis I, Kambas K, Rafail S, Chrysanthopoulou A, et al. 2010. Regulation of the autophagic machinery in human neutrophils. Eur. J. Immunol. 40:1461-72
175. Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, et al. 2004. Neutrophil extracellular traps kill bacteria. Science 303:1532-35
176. Fuchs TA, Abed U, Goosmann C, Hurwitz R, Schulze I, et al. 2007. Novel cell death program leads to neutrophil extracellular traps. J. Cell Biol. 176:231-41
177. Bakema JE, Ganzevles SH, Fluitsma DM, Schilham MW, Beelen RH, et al. 2011. Targeting FcαRI on polymorphonuclear cells induces tumor cell killing through autophagy. J. Immunol. 187:726-32
178. Mortensen M, Ferguson DJ, Edelmann M, Kessler B, Morten KJ, et al. 2010. Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivo. Proc. Natl. Acad. Sci. USA 107:832-37
179. Arsov I, Adebayo A, Kucerova-Levisohn M, Haye J, MacNeil M, et al. 2011. A role for autophagic protein beclin 1 early in lymphocyte development. J. Immunol. 186:2201-9
180. Tsubata T, Wu J, Honjo T. 1993. B-cell apoptosis induced by antigen receptor crosslinking is blocked by a T-cell signal through CD40. Nature 364:645-48
181. Hokazono Y, AdachiT, WablM, TadaN, Amagasa T, Tsubata T. 2003. Inhibitory coreceptors activated by antigens but not by anti-Ig heavy chain antibodies install requirement of costimulation throughCD40 for survival and proliferation of B cells. J. Immunol. 171:1835-43
182. Nimmerjahn F, Milosevic S, Behrends U, Jaffee EM, Pardoll DM, et al. 2003. Major histocompatibility complex class II-restricted presentation of a cytosolic antigen by autophagy. Eur. J. Immunol. 33:1250-59
183. Paludan C, Schmid D, Landthaler M, Vockerodt M, Kube D, et al. 2005. Endogenous MHC class II processing of a viral nuclear antigen after autophagy. Science 307:593-96
184. Watanabe K, Tsubata T. 2009. Autophagy connects antigen receptor signaling to costimulatory signaling in B lymphocytes. Autophagy 5:108-10
185. Chaturvedi A, Dorward D, Pierce SK. 2008. The B cell receptor governs the subcellular location of Toll-like receptor 9 leading to hyperresponses to DNA-containing antigens. Immunity 28:799-809
186. Hubbard VM, Valdor R, Patel B, Singh R, Cuervo AM, Macian F. 2010. Macroautophagy regulates energy metabolism during effector T cell activation. J. Immunol. 185:7349-57
187. Pua HH, Dzhagalov I, Chuck M, Mizushima N, He YW. 2007. A critical role for the autophagy gene Atg5 in T cell survival and proliferation. J. Exp. Med. 204:25-31
188. Pua HH, Guo J, Komatsu M, He YW. 2009. Autophagy is essential for mitochondrial clearance in mature T lymphocytes. J. Immunol. 182:4046-55
189. Kyewski B, Klein L. 2006. A central role for central tolerance. Annu. Rev. Immunol. 24:571-606
190. Mao K, Wang K, Zhao M, Xu T, Klionsky DJ. 2011. Two MAPK-signaling pathways are required for mitophagy in Saccharomyces cerevisiae. J. Cell Biol. 193:755-67
191. Yang K, Neale G, Green DR, HeW, Chi H. 2011. The tumor suppressor Tsc1 enforces quiescence of naive T cells to promote immune homeostasis and function. Nat. Immunol. 12:888-97
192. Zhou X, Ikenoue T, Chen X, Li L, Inoki K, Guan KL. 2009. Rheb controls misfolded protein metabolism by inhibiting aggresome formation and autophagy. Proc. Natl. Acad. Sci. USA 106:8923-28
193. Li J, Liu R, Lei Y, Wang K, Lau QC, et al. 2010. Proteomic analysis revealed association of aberrant ROS signaling with suberoylanilide hydroxamic acid-induced autophagy in Jurkat T-leukemia cells. Autophagy 6:711-24
194. Hildeman DA, Mitchell T, Teague TK, Henson P, Day BJ, et al. 1999. Reactive oxygen species regulate activation-induced T cell apoptosis. Immunity 10:735-44
195. + transfer to mitochondria. Cell 142:270-83
196. Liang SH, ZhangW, McGrath BC, Zhang P, Cavener DR. 2006. PERK (eIF2αkinase) is required to activate the stress-activatedMAPKsand induce the expression of immediate-early genes upon disruption of ER calcium homoeostasis. Biochem. J. 393:201-9
197. Lepine S, Allegood JC, Park M, Dent P, Milstien S, Spiegel S. 2011. Sphingosine-1-phosphate phosphohydrolase-1 regulates ER stress-induced autophagy. Cell Death Differ. 18:350-61
198. Roussel BD, Irving JA, Ekeowa UI, Belorgey D, Haq I, et al. 2011. Unravelling the twists and turns of the serpinopathies. FEBS J. 278:3859-67
199. Davies MJ, Miranda E, Roussel BD, Kaufman RJ, Marciniak SJ, Lomas DA. 2009. Neuroserpin polymers activate NF-κB by a calcium signaling pathway that is independent of the unfolded protein response. J. Biol. Chem. 284:18202-9
200. Shimizu S, Kanaseki T, Mizushima N, Mizuta T, Arakawa-Kobayashi S, et al. 2004. Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat. Cell Biol. 6:1221-28
201. Yu L, Alva A, Su H, Dutt P, Freundt E, et al. 2004. Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8. Science 304:1500-2
202. Kroemer G, Levine B. 2008. Autophagic cell death: the story of a misnomer. Nat. Rev. Mol. Cell Biol. 9:1004-10
203. Pyo JO, Jang MH, Kwon YK, Lee HJ, Jun JI, et al. 2005. Essential roles of Atg5 and FADD in autophagic cell death: dissection of autophagic cell death into vacuole formation and cell death. J. Biol. Chem. 280:20722-29
204. SchwartenM, Mohrluder J, Ma P, StoldtM, Thielmann Y, et al. 2009. Nix directly binds to GABARAP: a possible crosstalk between apoptosis and autophagy. Autophagy 5:690-98
205. Hitomi J, Christofferson DE, NgA, Yao J, Degterev A, et al. 2008. Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway. Cell 135:1311-23
206. Pattingre S, Tassa A, Qu XP, Garuti R, Liang XH, et al. 2005. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122:927-39
207. Ch'en IL, Tsau JS, Molkentin JD, Komatsu M, Hedrick SM. 2011. Mechanisms of necroptosis in T cells. J. Exp. Med. 208:633-41
208. Leverrier S, Salvesen GS, Walsh CM. 2011. Enzymatically active single chain caspase-8 maintains T-cell survival during clonal expansion. Cell Death Differ. 18:90-98
209. Osborn SL, Diehl G, Han SJ, Xue L, Kurd N, et al. 2010. Fas-associated death domain (FADD) is a negative regulator of T-cell receptor-mediated necroptosis. Proc. Natl. Acad. Sci. USA 107:13034-39
210. Zhang N, He YW. 2005. An essential role for c-FLIP in the efficient development of mature T lymphocytes. J. Exp. Med. 202:395-404
211. Ch'en IL, Beisner DR, Degterev A, Lynch C, Yuan J, et al. 2008. Antigen-mediated T cell expansion regulated by parallel pathways of death. Proc. Natl. Acad. Sci. USA 105:17463-68
212. Degterev A, Hitomi J, Germscheid M, Ch'en IL, Korkina O, et al. 2008. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat. Chem. Biol. 4:313-21
213. Lin Y, Devin A, Rodriguez Y, Liu ZG. 1999. Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosis. Genes Dev. 13:2514-26
214. Tweten RK. 2005. Cholesterol-dependent cytolysins, a family of versatile pore-forming toxins. Infect. Immun. 73:6199-209
215. Meyer-Morse N, Robbins JR, Rae CS, Mochegova SN, Swanson MS, et al. 2010. Listeriolysin O is necessary and sufficient to induce autophagy during Listeria monocytogenes infection. PLo S ONE 5:e8610
216. Yoshikawa Y, Ogawa M, Hain T, Yoshida M, Fukumatsu M, et al. 2009. Listeria monocytogenes ActAmediated escape from autophagic recognition. Nat. Cell Biol. 11:1233-40
217. Burdette DL, Yarbrough ML, Orvedahl A, Gilpin CJ, OrthK. 2008. Vibrio parahaemolyticus orchestrates amultifaceted host cell infection by induction of autophagy, cell rounding, and then cell lysis. Proc. Natl. Acad. Sci. USA 105:12497-502
218. McLean JE, Wudzinska A, Datan E, Quaglino D, Zakeri Z. 2011. Flavivirus NS4A-induced autophagy protects cells against death and enhances virus replication. J. Biol. Chem. 286:22147-59
219. Tang H, Da L, Mao Y, Li Y, Li D, et al. 2009. Hepatitis B virus X protein sensitizes cells to starvationinduced autophagy via up-regulation of beclin 1 expression. Hepatology 49:60-71
220. Ke PY, Chen SS. 2011. Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro. J. Clin. Investig. 121:37-56
221. Gannage M, Dormann D, Albrecht R, Dengjel J, Torossi T, et al. 2009. Matrix protein 2 of influenza A virus blocks autophagosome fusion with lysosomes. Cell Host Microbe 6:367-80