Rab7A Is Required for Efficient Production of Infectious HIV-1


Retroviruses take advantage of cellular trafficking machineries to assemble and release new infectious particles. Rab proteins regulate specific steps in intracellular membrane trafficking by recruiting tethering, docking and fusion factors, as well as the actin- and microtubule-based motor proteins that facilitate vesicle traffic. Using virological tests and RNA interference targeting Rab proteins, we demonstrate that the late endosome-associated Rab7A is required for HIV-1 propagation. Analysis of the late steps of the HIV infection cycle shows that Rab7A regulates Env processing, the incorporation of mature Env glycoproteins into viral particles and HIV-1 infectivity. We also show that siRNA-mediated Rab7A depletion induces a BST2/Tetherin phenotype on HIV-1 release. BST2/Tetherin is a restriction factor that impedes HIV-1 release by tethering mature virus particles to the plasma membrane. Our results suggest that Rab7A contributes to the mechanism by which Vpu counteracts the restriction factor BST2/Tetherin and rescues HIV-1 release. Altogether, our results highlight new roles for a major regulator of the late endocytic pathway, Rab7A, in the late stages of the HIV-1 replication cycle.


Vyšlo v časopise: Rab7A Is Required for Efficient Production of Infectious HIV-1. PLoS Pathog 7(11): e32767. doi:10.1371/journal.ppat.1002347
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002347

Souhrn

Retroviruses take advantage of cellular trafficking machineries to assemble and release new infectious particles. Rab proteins regulate specific steps in intracellular membrane trafficking by recruiting tethering, docking and fusion factors, as well as the actin- and microtubule-based motor proteins that facilitate vesicle traffic. Using virological tests and RNA interference targeting Rab proteins, we demonstrate that the late endosome-associated Rab7A is required for HIV-1 propagation. Analysis of the late steps of the HIV infection cycle shows that Rab7A regulates Env processing, the incorporation of mature Env glycoproteins into viral particles and HIV-1 infectivity. We also show that siRNA-mediated Rab7A depletion induces a BST2/Tetherin phenotype on HIV-1 release. BST2/Tetherin is a restriction factor that impedes HIV-1 release by tethering mature virus particles to the plasma membrane. Our results suggest that Rab7A contributes to the mechanism by which Vpu counteracts the restriction factor BST2/Tetherin and rescues HIV-1 release. Altogether, our results highlight new roles for a major regulator of the late endocytic pathway, Rab7A, in the late stages of the HIV-1 replication cycle.


Zdroje

1. GoffSP 2007 Host factors exploited by retroviruses. Nat Rev Microbiol 5 253 263

2. MalimMHEmermanM 2008 HIV-1 accessory proteins–ensuring viral survival in a hostile environment. Cell Host Microbe 3 388 398

3. FreedEO 2004 HIV-1 and the host cell: an intimate association. Trends Microbiol 12 170 177

4. FacklerOTKrausslichHG 2006 Interactions of human retroviruses with the host cell cytoskeleton. Curr Opin Microbiol 9 409 415

5. ChuHWangJJSpearmanP 2009 Human immunodeficiency virus type-1 gag and host vesicular trafficking pathways. Curr Top Microbiol Immunol 339 67 84

6. OnoAAblanSDLockettSJNagashimaKFreedEO 2004 Phosphatidylinositol (4,5) bisphosphate regulates HIV-1 Gag targeting to the plasma membrane. Proc Natl Acad Sci U S A 101 14889 14894

7. SaadJSMillerJTaiJKimAGhanamRH 2006 Structural basis for targeting HIV-1 Gag proteins to the plasma membrane for virus assembly. Proc Natl Acad Sci U S A 103 11364 11369

8. BonifacinoJSTraubLM 2003 Signals for Sorting of Transmembrane Proteins to Endosomes and Lysosomes. Annu Rev Biochem 72 395 447

9. CamusGSegura-MoralesCMolleDLopez-VergesSBegon-PesciaC 2007 The clathrin adaptor complex AP-1 binds HIV-1 and MLV Gag and facilitates their budding. Mol Biol Cell 18 3193 3203

10. DongXLiHDerdowskiADingLBurnettA 2005 AP-3 directs the intracellular trafficking of HIV-1 Gag and plays a key role in particle assembly. Cell 120 663 674

11. AzevedoCBurtonARuiz-MateosEMarshMSaiardiA 2009 Inositol pyrophosphate mediated pyrophosphorylation of AP3B1 regulates HIV-1 Gag release. Proc Natl Acad Sci U S A 106 21161 21166

12. JoshiAGargHNagashimaKBonifacinoJSFreedEO 2008 GGA and Arf proteins modulate retrovirus assembly and release. Mol Cell 30 227 238

13. BogeMWyssSBonifacinoJSThaliM 1998 A membrane-proximal tyrosine-based signal mediates internalization of the HIV-1 envelope glycoprotein via interaction with the AP-2 clathrin adaptor. J Biol Chem 273 15773 15778

14. BylandRVancePJHoxieJAMarshM 2007 A Conserved Dileucine Motif Mediates Clathrin and AP-2-dependent Endocytosis of the HIV-1 Envelope Protein. Mol Biol Cell 18 414 425

15. WyssSBerlioz-TorrentCBogeMBlotGHoningS 2001 The highly conserved C-terminal dileucine motif in the cytosolic domain of the human immunodeficiency virus type 1 envelope glycoprotein is critical for its association with the AP-1 clathrin adaptor [correction of adapter]. J Virol 75 2982 2992

16. Berlioz-TorrentCShacklettBLErdtmannLDelamarreLBouchaertI 1999 Interactions of the cytoplasmic domains of human and simian retroviral transmembrane proteins with components of the clathrin adaptor complexes modulate intracellular and cell surface expression of envelope glycoproteins. J Virol 73 1350 1361

17. OhnoHAguilarRCFournierMCHenneckeSCossonP 1997 Interaction of endocytic signals from the HIV-1 envelope glycoprotein complex with members of the adaptor medium chain family. Virology 238 305 315

18. BlotGJanvierKLe PanseSBenarousRBerlioz-TorrentC 2003 Targeting of the human immunodeficiency virus type 1 envelope to the trans-Golgi network through binding to TIP47 is required for env incorporation into virions and infectivity. J Virol 77 6931 6945

19. BaubyHLopez-VergesSHoeffelGDelcroix-GeneteDJanvierK 2010 TIP47 is required for the production of infectious HIV-1 particles from primary macrophages. Traffic 11 455 467

20. Lopez-VergesSCamusGBlotGBeauvoirRBenarousR 2006 Tail-interacting protein TIP47 is a connector between Gag and Env and is required for Env incorporation into HIV-1 virions. Proc Natl Acad Sci U S A 103 14947 14952

21. CarltonJGMartin-SerranoJ 2007 Parallels between cytokinesis and retroviral budding: a role for the ESCRT machinery. Science 316 1908 1912

22. MoritaESandrinVChungHYMorhamSGGygiSP 2007 Human ESCRT and ALIX proteins interact with proteins of the midbody and function in cytokinesis. EMBO J 26 4215 4227

23. RaiborgCStenmarkH 2009 The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins. Nature 458 445 452

24. GarrusJEvon SchwedlerUKPornillosOWMorhamSGZavitzKH 2001 Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding. Cell 107 55 65

25. von SchwedlerUKStuchellMMullerBWardDMChungHY 2003 The protein network of HIV budding. Cell 114 701 713

26. StrackBCalistriACraigSPopovaEGottlingerHG 2003 AIP1/ALIX is a binding partner for HIV-1 p6 and EIAV p9 functioning in virus budding. Cell 114 689 699

27. Martin-SerranoJZangTBieniaszPD 2001 HIV-1 and Ebola virus encode small peptide motifs that recruit Tsg101 to sites of particle assembly to facilitate egress. Nat Med 7 1313 1319

28. NeilSJZangTBieniaszPD 2008 Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 451 425 430

29. Van DammeNGoffDKatsuraCJorgensonRLMitchellR 2008 The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein. Cell Host Microbe 3 245 252

30. JanvierKPelchen-MatthewsARenaudJBCailletMMarshM 2011 The ESCRT-0 Component HRS is Required for HIV-1 Vpu-Mediated BST-2/Tetherin Downregulation. PLoS Pathog 7 e1001265

31. StenmarkH 2009 Rab GTPases as coordinators of vesicle traffic. Nat Rev Mol Cell Biol 10 513 525

32. ZerialMMcBrideH 2001 Rab proteins as membrane organizers. Nat Rev Mol Cell Biol 2 107 117

33. PfefferS 2005 A model for Rab GTPase localization. Biochem Soc Trans 33 627 630

34. CaiHReinischKFerro-NovickS 2007 Coats, tethers, Rabs, and SNAREs work together to mediate the intracellular destination of a transport vesicle. Dev Cell 12 671 682

35. ChavrierPPartonRGHauriHPSimonsKZerialM 1990 Localization of low molecular weight GTP binding proteins to exocytic and endocytic compartments. Cell 62 317 329

36. PressBFengYHoflackBWandinger-NessA 1998 Mutant Rab7 causes the accumulation of cathepsin D and cation- independent mannose 6-phosphate receptor in an early endocytic compartment. J Cell Biol 140 1075 1089

37. BucciCThomsenPNicozianiPMcCarthyJvan DeursB 2000 Rab7: a key to lysosome biogenesis. Mol Biol Cell 11 467 480

38. VitelliRSantilloMLatteroDChiarielloMBifulcoM 1997 Role of the small GTPase Rab7 in the late endocytic pathway. J Biol Chem 272 4391 4397

39. FengYPressBWandinger-NessA 1995 Rab 7: an important regulator of late endocytic membrane traffic. J Cell Biol 131 1435 1452

40. LebrandCCortiMGoodsonHCossonPCavalliV 2002 Late endosome motility depends on lipids via the small GTPase Rab7. EMBO J 21 1289 1300

41. CeresaBPBahrSJ 2006 rab7 activity affects epidermal growth factor:epidermal growth factor receptor degradation by regulating endocytic trafficking from the late endosome. J Biol Chem 281 1099 1106

42. WangTMingZXiaochunWHongW 2011 Rab7: role of its protein interaction cascades in endo-lysosomal traffic. Cell Signal 23 516 521

43. HarrisonREBucciCVieiraOVSchroerTAGrinsteinS 2003 Phagosomes fuse with late endosomes and/or lysosomes by extension of membrane protrusions along microtubules: role of Rab7 and RILP. Mol Cell Biol 23 6494 6506

44. VieiraOVBucciCHarrisonRETrimbleWSLanzettiL 2003 Modulation of Rab5 and Rab7 recruitment to phagosomes by phosphatidylinositol 3-kinase. Mol Cell Biol 23 2501 2514

45. GutierrezMGMunafoDBBeronWColomboMI 2004 Rab7 is required for the normal progression of the autophagic pathway in mammalian cells. J Cell Sci 117 2687 2697

46. JagerSBucciCTanidaIUenoTKominamiE 2004 Role for Rab7 in maturation of late autophagic vacuoles. J Cell Sci 117 4837 4848

47. JohanssonMRochaNZwartWJordensIJanssenL 2007 Activation of endosomal dynein motors by stepwise assembly of Rab7-RILP-p150Glued, ORP1L, and the receptor betalll spectrin. J Cell Biol 176 459 471

48. MurrayJLMavrakisMMcDonaldNJYillaMShengJ 2005 Rab9 GTPase is required for replication of human immunodeficiency virus type 1, filoviruses, and measles virus. J Virol 79 11742 11751

49. BrassALDykxhoornDMBenitaYYanNEngelmanA 2008 Identification of host proteins required for HIV infection through a functional genomic screen. Science 319 921 926

50. MolleDSegura-MoralesCCamusGBerlioz-TorrentCKjemsJ 2009 Endosomal Trafficking of HIV-1 Gag and Genomic RNAs Regulates Viral Egress. J Biol Chem 284 19727 19743

51. LehmannMMilevMPAbrahamyanLYaoXJPanteN 2009 Intracellular transport of human immunodeficiency virus type 1 genomic RNA and viral production are dependent on dynein motor function and late endosome positioning. J Biol Chem 284 14572 14585

52. GoffinetCAllespachIHomannSTervoHMHabermannA 2009 HIV-1 antagonism of CD317 is species specific and involves Vpu-mediated proteasomal degradation of the restriction factor. Cell Host Microbe 5 285 297

53. MangeatBGers-HuberGLehmannMZuffereyMLubanJ 2009 HIV-1 Vpu neutralizes the antiviral factor Tetherin/BST-2 by binding it and directing its beta-TrCP2-dependent degradation. PLoS Pathog 5 e1000574

54. MitchellRSKatsuraCSkaskoMAFitzpatrickKLauD 2009 Vpu antagonizes BST-2-mediated restriction of HIV-1 release via beta-TrCP and endo-lysosomal trafficking. PLoS Pathog 5 e1000450

55. Perez-CaballeroDZangTEbrahimiAMcNattMWGregoryDA 2009 Tetherin inhibits HIV-1 release by directly tethering virions to cells. Cell 139 499 511

56. DouglasJLViswanathanKMcCarrollMNGustinJKFruhK 2009 Vpu directs the degradation of the human immunodeficiency virus restriction factor BST-2/Tetherin via a {beta}TrCP-dependent mechanism. J Virol 83 7931 7947

57. NeilSJSandrinVSundquistWIBieniaszPD 2007 An interferon-alpha-induced tethering mechanism inhibits HIV-1 and Ebola virus particle release but is counteracted by the HIV-1 Vpu protein. Cell Host Microbe 2 193 203

58. BishopNHormanAWoodmanP 2002 Mammalian class E vps proteins recognize ubiquitin and act in the removal of endosomal protein-ubiquitin conjugates. J Cell Biol 157 91 101

59. RaiborgCMalerodLPedersenNMStenmarkH 2008 Differential functions of Hrs and ESCRT proteins in endocytic membrane trafficking. Exp Cell Res 314 801 813

60. VanlandinghamPACeresaBP 2009 Rab7 regulates late endocytic trafficking downstream of multivesicular body biogenesis and cargo sequestration. J Biol Chem 284 12110 12124

61. BolteSCordelieresFP 2006 A guided tour into subcellular colocalization analysis in light microscopy. J Microsc 224 213 232

62. IwabuYFujitaHKinomotoMKanekoKIshizakaY 2009 HIV-1 accessory protein Vpu internalizes cell-surface BST-2/tetherin through transmembrane interactions leading to lysosomes. J Biol Chem 284 35060 35072

63. VidricaireGTremblayMJ 2005 Rab5 and Rab7, but not ARF6, govern the early events of HIV-1 infection in polarized human placental cells. J Immunol 175 6517 6530

64. HallenbergerSBoschVAnglikerHShawEKlenkHD 1992 Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160. Nature 360 358 361

65. MoulardMDecrolyE 2000 Maturation of HIV envelope glycoprotein precursors by cellular endoproteases. Biochim Biophys Acta 1469 121 132

66. RollasonRKorolchukVHamiltonCSchuPBantingG 2007 Clathrin-mediated endocytosis of a lipid-raft-associated protein is mediated through a dual tyrosine motif. J Cell Sci 120 3850 3858

67. SchmidtSFritzJVBitzegeioJFacklerOTKepplerOT 2011 HIV-1 Vpu Blocks Recycling and Biosynthetic Transport of the Intrinsic Immunity Factor CD317/Tetherin To Overcome the Virion Release Restriction. MBio 2 e00036 11

68. TokarevAAMunguiaJGuatelliJC 2011 Serine-threonine ubiquitination mediates downregulation of BST-2/tetherin and relief of restricted virion release by HIV-1 Vpu. J Virol 85 51 63

69. PardieuCViganRWilsonSJCalviAZangT 2010 The RING-CH ligase K5 antagonizes restriction of KSHV and HIV-1 particle release by mediating ubiquitin-dependent endosomal degradation of tetherin. PLoS Pathog 6 e1000843

70. SilvaEAu-YeungHWVan GoethemEBurdenJFrancNC 2007 Requirement for a Drosophila E3-ubiquitin ligase in phagocytosis of apoptotic cells. Immunity 27 585 596

71. MiyakawaKRyoAMurakamiTOhbaKYamaokaS 2009 BCA2/Rabring7 promotes tetherin-dependent HIV-1 restriction. PLoS Pathog 5 e1000700

72. MizunoKKitamuraASasakiT 2003 Rabring7, a novel Rab7 target protein with a RING finger motif. Mol Biol Cell 14 3741 3752

73. SakaneAHatakeyamaSSasakiT 2007 Involvement of Rabring7 in EGF receptor degradation as an E3 ligase. Biochem Biophys Res Commun 357 1058 1064

74. VonderheitAHeleniusA 2005 Rab7 associates with early endosomes to mediate sorting and transport of Semliki forest virus to late endosomes. PLoS Biol 3 e233

75. HarbisonCELyiSMWeichertWSParrishCR 2009 Early steps in cell infection by parvoviruses: host-specific differences in cell receptor binding but similar endosomal trafficking. J Virol 83 10504 10514

76. van der SchaarHMRustMJChenCvan der Ende-MetselaarHWilschutJ 2008 Dissecting the cell entry pathway of dengue virus by single-particle tracking in living cells. PLoS Pathog 4 e1000244

77. KrishnanMNSukumaranBPalUAgaisseHMurrayJL 2007 Rab 5 is required for the cellular entry of dengue and West Nile viruses. J Virol 81 4881 4885

78. KlimkaitTStrebelKHogganMDMartinMAOrensteinJM 1990 The human immunodeficiency virus type 1-specific protein vpu is required for efficient virus maturation and release. J Virol 64 621 629

79. BrusselASonigoP 2004 Evidence for gene expression by unintegrated human immunodeficiency virus type 1 DNA species. J Virol 78 11263 11271

80. BacheKGBrechAMehlumAStenmarkH 2003 Hrs regulates multivesicular body formation via ESCRT recruitment to endosomes. J Cell Biol 162 435 442

81. DenekaMPelchen-MatthewsABylandRRuiz-MateosEMarshM 2007 In macrophages, HIV-1 assembles into an intracellular plasma membrane domain containing the tetraspanins CD81, CD9, and CD53. J Cell Biol 177 329 341

82. SlotJWGeuzeHJ 2007 Cryosectioning and immunolabeling. Nat Protoc 2 2480 2491

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