IRGM Is a Common Target of RNA Viruses that Subvert the Autophagy Network

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Autophagy is a conserved degradative pathway used as a host defense mechanism against intracellular pathogens. However, several viruses can evade or subvert autophagy to insure their own replication. Nevertheless, the molecular details of viral interaction with autophagy remain largely unknown. We have determined the ability of 83 proteins of several families of RNA viruses (Paramyxoviridae, Flaviviridae, Orthomyxoviridae, Retroviridae and Togaviridae), to interact with 44 human autophagy-associated proteins using yeast two-hybrid and bioinformatic analysis. We found that the autophagy network is highly targeted by RNA viruses. Although central to autophagy, targeted proteins have also a high number of connections with proteins of other cellular functions. Interestingly, immunity-associated GTPase family M (IRGM), the most targeted protein, was found to interact with the autophagy-associated proteins ATG5, ATG10, MAP1CL3C and SH3GLB1. Strikingly, reduction of IRGM expression using small interfering RNA impairs both Measles virus (MeV), Hepatitis C virus (HCV) and human immunodeficiency virus-1 (HIV-1)-induced autophagy and viral particle production. Moreover we found that the expression of IRGM-interacting MeV-C, HCV-NS3 or HIV-NEF proteins per se is sufficient to induce autophagy, through an IRGM dependent pathway. Our work reveals an unexpected role of IRGM in virus-induced autophagy and suggests that several different families of RNA viruses may use common strategies to manipulate autophagy to improve viral infectivity.

Vyšlo v časopise: IRGM Is a Common Target of RNA Viruses that Subvert the Autophagy Network. PLoS Pathog 7(12): e32767. doi:10.1371/journal.ppat.1002422
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002422

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Zdroje

1. XieZKlionskyDJ 2007 Autophagosome formation: core machinery and adaptations. Nat Cell Biol 9 1102 1109

2. LevineBKlionskyDJ 2004 Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell 6 463 477

3. FuruyaNYuJByfieldMPattingreSLevineB 2005 The evolutionarily conserved domain of Beclin 1 is required for Vps34 binding, autophagy and tumor suppressor function. Autophagy 1 46 52

4. KiharaAKabeyaYOhsumiYYoshimoriT 2001 Beclin-phosphatidylinositol 3-kinase complex functions at the trans-Golgi network. EMBO Rep 2 330 335

5. ZengXOvermeyerJHMalteseWA 2006 Functional specificity of the mammalian Beclin-Vps34 PI 3-kinase complex in macroautophagy versus endocytosis and lysosomal enzyme trafficking. J Cell Sci 119 259 270

6. FujitaNItohTOmoriHFukudaMNodaT 2008 The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy. Mol Biol Cell 19 2092 2100

7. HanadaTNodaNNSatomiYIchimuraYFujiokaY 2007 The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy. J Biol Chem 282 37298 37302

8. DereticVLevineB 2009 Autophagy, immunity, and microbial adaptations. Cell Host Microbe 5 527 549

9. LevineBMizushimaNVirginHW 2011 Autophagy in immunity and inflammation. Nature 469 323 335

10. AmanoANakagawaIYoshimoriT 2006 Autophagy in innate immunity against intracellular bacteria. J Biochem (Tokyo) 140 161 166

11. NakagawaIAmanoAMizushimaNYamamotoAYamaguchiH 2004 Autophagy defends cells against invading group A Streptococcus. Science 306 1037 1040

12. BirminghamCLSmithACBakowskiMAYoshimoriTBrumellJH 2006 Autophagy controls Salmonella infection in response to damage to the Salmonella-containing vacuole. J Biol Chem 281 11374 11383

13. OrvedahlAMacPhersonSSumpterRJrTalloczyZZouZ 2010 Autophagy protects against Sindbis virus infection of the central nervous system. Cell Host Microbe 7 115 127

14. ShellySLukinovaNBambinaSBermanACherryS 2009 Autophagy is an essential component of Drosophila immunity against vesicular stomatitis virus. Immunity 30 588 598

15. LeeHKLundJMRamanathanBMizushimaNIwasakiA 2007 Autophagy-dependent viral recognition by plasmacytoid dendritic cells. Science 315 1398 1401

16. JagannathCLindseyDRDhandayuthapaniSXuYHunterRLJr 2009 Autophagy enhances the efficacy of BCG vaccine by increasing peptide presentation in mouse dendritic cells. Nat Med 15 267 276

17. PaludanCSchmidDLandthalerMVockerodtMKubeD 2005 Endogenous MHC class II processing of a viral nuclear antigen after autophagy. Science 307 593 596

18. SchmidDPypaertMMunzC 2007 Antigen-loading compartments for major histocompatibility complex class II molecules continuously receive input from autophagosomes. Immunity 26 79 92

19. Ait-GoughoulteMKandaTMeyerKRyerseJSRayRB 2008 Hepatitis C virus genotype 1a growth and induction of autophagy. J Virol 82 2241 2249

20. DreuxMGastaminzaPWielandSFChisariFV 2009 The autophagy machinery is required to initiate hepatitis C virus replication. Proc Natl Acad Sci U S A 106 14046 14051

21. GannageMDormannDAlbrechtRDengjelJTorossiT 2009 Matrix protein 2 of influenza A virus blocks autophagosome fusion with lysosomes. Cell Host Microbe 6 367 380

22. JacksonWTGiddingsTHJrTaylorMPMulinyaweSRabinovitchM 2005 Subversion of cellular autophagosomal machinery by RNA viruses. PLoS Biol 3 e156

23. EspertLDenizotMGrimaldiMRobert-HebmannVGayB 2006 Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to CXCR4. J Clin Invest 116 2161 2172

24. KyeiGBDinkinsCDavisASRobertsESinghSB 2009 Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages. J Cell Biol 186 255 268

25. LeeYRLeiHYLiuMTWangJRChenSH 2008 Autophagic machinery activated by dengue virus enhances virus replication. Virology 374 240 248

26. McCarrollSAHuettAKuballaPChilewskiSDLandryA 2008 Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease. Nat Genet 40 1107 1112

27. SinghSBDavisASTaylorGADereticV 2006 Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science 313 1438 1441

28. BrestPLapaquettePSouidiMLebrigandKCesaroA 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 43 242 245

29. SinghSBOrnatowskiWVergneINaylorJDelgadoM 2010 Human IRGM regulates autophagy and cell-autonomous immunity functions through mitochondria. Nat Cell Biol 12 1154 1165

30. NavratilVde ChasseyBMeynielLDelmotteSGautierC 2009 VirHostNet: a knowledge base for the management and the analysis of proteome-wide virus-host interaction networks. Nucleic Acids Res 37 D661 668

31. NavratilVde ChasseyBMeynielLPradezynskiFAndreP 2010 System-level comparison of protein-protein interactions between viruses and the human type I interferon system network. J Proteome Res 9 3527 3536

32. JoubertPEMeiffrenGGregoireIPPontiniGRichettaC 2009 Autophagy induction by the pathogen receptor CD46. Cell Host Microbe 6 354 366

33. SirDChenWLChoiJWakitaTYenTS 2008 Induction of incomplete autophagic response by hepatitis C virus via the unfolded protein response. Hepatology 48 1054 1061

34. EspertLVarbanovMRobert-HebmannVSagnierSRobbinsI 2009 Differential role of autophagy in CD4 T cells and macrophages during X4 and R5 HIV-1 infection. PLoS One 4 e5787

35. BehrendsCSowaMEGygiSPHarperJW 2010 Network organization of the human autophagy system. Nature 466 68 76

36. ZhengYTShahnazariSBrechALamarkTJohansenT 2009 The adaptor protein p62/SQSTM1 targets invading bacteria to the autophagy pathway. J Immunol 183 5909 5916

37. BellotGGarcia-MedinaRGounonPChicheJRouxD 2009 Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol Cell Biol 29 2570 2581

38. YuCWangLLvBLuYZengL 2008 TMEM74, a lysosome and autophagosome protein, regulates autophagy. Biochem Biophys Res Commun 369 622 629

39. TaylorGAFengCGSherA 2007 Control of IFN-gamma-mediated host resistance to intracellular pathogens by immunity-related GTPases (p47 GTPases). Microbes Infect 9 1644 1651

40. BekpenCHunnJPRohdeCParvanovaIGuethleinL 2005 The interferon-inducible p47 (IRG) GTPases in vertebrates: loss of the cell autonomous resistance mechanism in the human lineage. Genome Biol 6 R92

41. BurtonPRClaytonDGCardonLRCraddockNDeloukasP 2007 Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat Genet 39 1329 1337

42. IntemannCDThyeTNiemannSBrowneENAmanua ChinbuahM 2009 Autophagy gene variant IRGM -261T contributes to protection from tuberculosis caused by Mycobacterium tuberculosis but not by M. africanum strains. PLoS Pathog 5 e1000577

43. ParkesMBarrettJCPrescottNJTremellingMAndersonCA 2007 Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. Nat Genet 39 830 832

44. JounaiNTakeshitaFKobiyamaKSawanoAMiyawakiA 2007 The Atg5 Atg12 conjugate associates with innate antiviral immune responses. Proc Natl Acad Sci U S A 104 14050 14055

45. KarbowskiMJeongSYYouleRJ 2004 Endophilin B1 is required for the maintenance of mitochondrial morphology. J Cell Biol 166 1027 1039

46. LapaquettePGlasserALHuettAXavierRJDarfeuille-MichaudA 2010 Crohn's disease-associated adherent-invasive E. coli are selectively favoured by impaired autophagy to replicate intracellularly. Cell Microbiol 12 99 113

47. TiwariSChoiHPMatsuzawaTPypaertMMacMickingJD 2009 Targeting of the GTPase Irgm1 to the phagosomal membrane via PtdIns(3,4)P(2) and PtdIns(3,4,5)P(3) promotes immunity to mycobacteria. Nat Immunol 10 907 917

48. PelletJTafforeauLLucas-HouraniMNavratilVMeynielL 2010 ViralORFeome: an integrated database to generate a versatile collection of viral ORFs. Nucleic Acids Res 38 D371 378

49. KatoTDateTMurayamaAMorikawaKAkazawaD 2006 Cell culture and infection system for hepatitis C virus. Nat Protoc 1 2334 2339