SIV Nef Proteins Recruit the AP-2 Complex to Antagonize Tetherin and Facilitate Virion Release

English version České info

Lentiviral Nef proteins have multiple functions and are important for viral pathogenesis. Recently, Nef proteins from many simian immunodefiency viruses were shown to antagonize a cellular antiviral protein, named Tetherin, that blocks release of viral particles from the cell surface. However, the mechanism by which Nef antagonizes Tetherin is unknown. Here, using related Nef proteins that differ in their ability to antagonize Tetherin, we identify three amino-acids in the C-terminal domain of Nef that are critical specifically for its ability to antagonize Tetherin. Additionally, divergent Nef proteins bind to the AP-2 clathrin adaptor complex, and we show that residues important for this interaction are required for Tetherin antagonism, downregulation of Tetherin from the cell surface and removal of Tetherin from sites of particle assembly. Accordingly, depletion of AP-2 using RNA interference impairs the ability of Nef to antagonize Tetherin, demonstrating that AP-2 recruitment is required for Nef proteins to counteract this antiviral protein.

Vyšlo v časopise: SIV Nef Proteins Recruit the AP-2 Complex to Antagonize Tetherin and Facilitate Virion Release. PLoS Pathog 7(5): e32767. doi:10.1371/journal.ppat.1002039
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002039

Souhrn

Zdroje

1. KirchhoffF 2010 Immune evasion and counteraction of restriction factors by HIV-1 and other primate lentiviruses. Cell Host Microbe 8 55 67

2. BergamaschiAAyindeDDavidALe RouzicEMorelM 2009 The human immunodeficiency virus type 2 Vpx protein usurps the CUL4A-DDB1 DCAF1 ubiquitin ligase to overcome a postentry block in macrophage infection. J Virol 83 4854 4860

3. SharovaNWuYZhuXStranskaRKaushikR 2008 Primate lentiviral Vpx commandeers DDB1 to counteract a macrophage restriction. PLoS Pathog 4 e1000057

4. SrivastavaSSwansonSKManelNFlorensLWashburnMP 2008 Lentiviral Vpx accessory factor targets VprBP/DCAF1 substrate adaptor for cullin 4 E3 ubiquitin ligase to enable macrophage infection. PLoS Pathog 4 e1000059

5. KupzigSKorolchukVRollasonRSugdenAWildeA 2003 Bst-2/HM1.24 is a raft-associated apical membrane protein with an unusual topology. Traffic 4 694 709

6. SchubertHLZhaiQSandrinVEckertDMGarcia-MayaM 2010 Structural and functional studies on the extracellular domain of BST2/tetherin in reduced and oxidized conformations. Proc Natl Acad Sci U S A 107 17951 17956

7. SwieckiMScheafferSMAllaireMFremontDHColonnaM 2010 Structural and biophysical analysis of BST-2/tetherin ectodomains reveals an evolutionary conserved design to inhibit virus release. J Biol Chem 286 2987 2997

8. YangHWangJJiaXMcNattMWZangT 2010 Structural insight into the mechanisms of enveloped virus tethering by tetherin. Proc Natl Acad Sci U S A 107 18428 18432

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

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

11. 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

12. JouvenetNNeilSJZhadinaMZangTKratovacZ 2009 Broad-spectrum inhibition of retroviral and filoviral particle release by tetherin. J Virol 83 1837 1844

13. KaletskyRLFrancicaJRAgrawal-GamseCBatesP 2009 Tetherin-mediated restriction of filovirus budding is antagonized by the Ebola glycoprotein. Proc Natl Acad Sci U S A 106 2886 2891

14. MansouriMViswanathanKDouglasJLHinesJGustinJ 2009 Molecular mechanism of BST2/tetherin downregulation by K5/MIR2 of Kaposi's sarcoma-associated herpesvirus. J Virol 83 9672 9681

15. 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

16. SakumaTNodaTUrataSKawaokaYYasudaJ 2009 Inhibition of Lassa and Marburg virus production by tetherin. J Virol 83 2382 2385

17. WeidnerJMJiangDPanXBChangJBlockTM 2010 Interferon-induced cell membrane proteins, IFITM3 and tetherin, inhibit vesicular stomatitis virus infection via distinct mechanisms. J Virol 84 12646 12657

18. JiaBSerra-MorenoRNeidermyerWRahmbergAMackeyJ 2009 Species-specific activity of SIV Nef and HIV-1 Vpu in overcoming restriction by tetherin/BST2. PLoS Pathog 5 e1000429

19. Le TortorecANeilSJ 2009 Antagonism to and intracellular sequestration of human tetherin by the human immunodeficiency virus type 2 envelope glycoprotein. J Virol 83 11966 11978

20. SauterDSchindlerMSpechtALandfordWNMunchJ 2009 Tetherin-driven adaptation of Vpu and Nef function and the evolution of pandemic and nonpandemic HIV-1 strains. Cell Host Microbe 6 409 421

21. ZhangFWilsonSJLandfordWCVirgenBGregoryD 2009 Nef proteins from simian immunodeficiency viruses are tetherin antagonists. Cell Host Microbe 6 54 67

22. SharpPMShawGMHahnBH 2005 Simian immunodeficiency virus infection of chimpanzees. J Virol 79 3891 3902

23. LimESMalikHSEmermanM 2010 Ancient adaptive evolution of tetherin shaped the functions of Vpu and Nef in human immunodeficiency virus and primate lentiviruses. J Virol 84 7124 7134

24. YangSJLopezLAHauserHExlineCMHaworthKG 2010 Anti-tetherin activities in Vpu-expressing primate lentiviruses. Retrovirology 7 13

25. GeyerMFacklerOTPeterlinMB 2001 Structure-function relationships in HIV-1 Nef. EMBO Rep 21 580 585

26. BlagoveshchenskayaADThomasLFeliciangeliSFHungCHThomasG 2002 HIV-1 Nef downregulates MHC-I by a PACS-1- and PI3K-regulated ARF6 endocytic pathway. Cell 111 853 866

27. MangasarianAPiguetVWangJKChenYLTronoD 1999 Nef-induced CD4 and major histocompatibility complex class I (MHC-I) down-regulation are governed by distinct determinants: N-terminal alpha helix and proline repeat of Nef selectively regulate MHC-I trafficking. J Virol 73 1964 1973

28. KirchhoffFSchindlerMSpechtAArhelNMunchJ 2008 Role of Nef in primate lentiviral immunopathogenesis. Cell Mol Life Sci 65 2621 2636

29. Le GallSErdtmannLBenichouSBerlioz-TorrentCLiuL 1998 Nef interacts with the mu subunit of clathrin adaptor complexes and reveals a cryptic sorting signal in MHC I molecules. Immunity 8 483 495

30. RoethJFWilliamsMKasperMRFilzenTMCollinsKL 2004 HIV-1 Nef disrupts MHC-I trafficking by recruiting AP-1 to the MHC-I cytoplasmic tail. J Cell Biol 167 903 913

31. SchwartzOMarechalVLe GallSLemonnierFHeardJM 1996 Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein. Nat Med 2 338 342

32. AikenCKonnerJLandauNRLenburgMETronoD 1994 Nef induces CD4 endocytosis: requirement for a critical dileucine motif in the membrane-proximal CD4 cytoplasmic domain. Cell 76 853 864

33. BresnahanPAYonemotoWFerrellSWilliams-HermanDGeleziunasR 1998 A dileucine motif in HIV-1 Nef acts as an internalization signal for CD4 downregulation and binds the AP-1 clathrin adaptor. Curr Biol 8 1235 1238

34. CraigHMPandoriMWGuatelliJC 1998 Interaction of HIV-1 Nef with the cellular dileucine-based sorting pathway is required for CD4 down-regulation and optimal viral infectivity. Proc Natl Acad Sci U S A 95 11229 11234

35. GreenbergMDeTulleoLRapoportISkowronskiJKirchhausenT 1998 A dileucine motif in HIV-1 Nef is essential for sorting into clathrin-coated pits and for downregulation of CD4. Curr Biol 8 1239 1242

36. ChaudhuriRLindwasserOWSmithWJHurleyJHBonifacinoJS 2007 Downregulation of CD4 by human immunodeficiency virus type 1 Nef is dependent on clathrin and involves direct interaction of Nef with the AP2 clathrin adaptor. J Virol 81 3877 3890

37. LindwasserOWSmithWJChaudhuriRYangPHurleyJH 2008 A diacidic motif in human immunodeficiency virus type 1 Nef is a novel determinant of binding to AP-2. J Virol 82 1166 1174

38. BresnahanPAYonemotoWGreeneWC 1999 Cutting edge: SIV Nef protein utilizes both leucine- and tyrosine-based protein sorting pathways for down-regulation of CD4. J Immunol 163 2977 2981

39. LockMGreenbergMEIafrateAJSwigutTMuenchJ 1999 Two elements target SIV Nef to the AP-2 clathrin adaptor complex, but only one is required for the induction of CD4 endocytosis. EMBO J 18 2722 2733

40. GrzesiekSStahlSJWingfieldPTBaxA 1996 The CD4 determinant for downregulation by HIV-1 Nef directly binds to Nef. Mapping of the Nef binding surface by NMR. Biochemistry 35 10256 10261

41. LiuLXHevekerNFacklerOTAroldSLe GallS 2000 Mutation of a conserved residue (D123) required for oligomerization of human immunodeficiency virus type 1 Nef protein abolishes interaction with human thioesterase and results in impairment of Nef biological functions. J Virol 74 5310 5319

42. SawaiETKhanIHMontbriandPMPeterlinBMCheng-MayerC 1996 Activation of PAK by HIV and SIV Nef: importance for AIDS in rhesus macaques. Curr Biol 6 1519 1527

43. ChaudhuriRMatteraRLindwasserOWRobinsonMSBonifacinoJS 2009 A basic patch on alpha-adaptin is required for binding of human immunodeficiency virus type 1 Nef and cooperative assembly of a CD4-Nef-AP-2 complex. J Virol 83 2518 2530

44. TraubLM 2009 Tickets to ride: selecting cargo for clathrin-regulated internalization. Nat Rev Mol Cell Biol 10 583 596

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

46. MasuyamaNKuronitaTTanakaRMutoTHirotaY 2009 HM1.24 is internalized from lipid rafts by clathrin-mediated endocytosis through interaction with alpha-adaptin. J Biol Chem 284 15927 15941

47. Serra-MorenoRJiaBBreedMAlvarezXEvansDT 2011 Compensatory changes in the cytoplasmic tail of gp41 confer resistance to tetherin/BST-2 in a pathogenic nef-deleted SIV. Cell Host Microbe 9 46 57

48. DeaconNJTsykinASolomonASmithKLudford-MentingM 1995 Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients. Science 270 988 991

49. KestlerHW3rdRinglerDJMoriKPanicaliDLSehgalPK 1991 Importance of the nef gene for maintenance of high virus loads and for development of AIDS. Cell 65 651 662

50. KirchhoffFGreenoughTCBrettlerDBSullivanJLDesrosiersRC 1995 Brief report: absence of intact nef sequences in a long-term survivor with nonprogressive HIV-1 infection. N Engl J Med 332 228 232

51. 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

52. 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

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

54. DemaisonCParsleyKBrounsGScherrMBattmerK 2002 High-level transduction and gene expression in hematopoietic repopulating cells using a human immunodeficiency [correction of imunodeficiency] virus type 1-based lentiviral vector containing an internal spleen focus forming virus promoter. Hum Gene Ther 13 803 813

55. McNattMWZangTHatziioannouTBartlettMFofanaIB 2009 Species-specific activity of HIV-1 Vpu and positive selection of tetherin transmembrane domain variants. PLoS Pathog 5 e1000300

56. RoseJJJanvierKChandrasekharSSekalyRPBonifacinoJS 2005 CD4 down-regulation by HIV-1 and simian immunodeficiency virus (SIV) Nef proteins involves both internalization and intracellular retention mechanisms. J Biol Chem 280 7413 7426

57. SwigutTIafrateAJMuenchJKirchhoffFSkowronskiJ 2000 Simian and human immunodeficiency virus Nef proteins use different surfaces to downregulate class I major histocompatibility complex antigen expression. J Virol 74 5691 5701

58. BogerdHPFridellRABlairWSCullenBR 1993 Genetic evidence that the Tat proteins of human immunodeficiency virus types 1 and 2 can multimerize in the eukaryotic cell nucleus. J Virol 67 5030 5034