APOBEC3A Is a Specific Inhibitor of the Early Phases of HIV-1 Infection in Myeloid Cells

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Myeloid cells play numerous roles in HIV-1 pathogenesis serving as a vehicle for viral spread and as a viral reservoir. Yet, cells of this lineage generally resist HIV-1 infection when compared to cells of other lineages, a phenomenon particularly acute during the early phases of infection. Here, we explore the role of APOBEC3A on these steps. APOBEC3A is a member of the APOBEC3 family that is highly expressed in myeloid cells, but so far lacks a known antiviral effect against retroviruses. Using ectopic expression of APOBEC3A in established cell lines and specific silencing in primary macrophages and dendritic cells, we demonstrate that the pool of APOBEC3A in target cells inhibits the early phases of HIV-1 infection and the spread of replication-competent R5-tropic HIV-1, specifically in cells of myeloid origins. In these cells, APOBEC3A affects the amount of vDNA synthesized over the course of infection. The susceptibility to the antiviral effect of APOBEC3A is conserved among primate lentiviruses, although the viral protein Vpx coded by members of the SIV_SM/HIV-2 lineage provides partial protection from APOBEC3A during infection. Our results indicate that APOBEC3A is a previously unrecognized antiviral factor that targets primate lentiviruses specifically in myeloid cells and that acts during the early phases of infection directly in target cells. The findings presented here open up new venues on the role of APOBEC3A during HIV infection and pathogenesis, on the role of the cellular context in the regulation of the antiviral activities of members of the APOBEC3 family and more generally on the natural functions of APOBEC3A.

Vyšlo v časopise: APOBEC3A Is a Specific Inhibitor of the Early Phases of HIV-1 Infection in Myeloid Cells. PLoS Pathog 7(9): e32767. doi:10.1371/journal.ppat.1002221
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002221

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1. AlbinJSHarrisRS 2010 Interactions of host APOBEC3 restriction factors with HIV-1 in vivo: implications for therapeutics. Expert Rev Mol Med 12 e4

2. SheehyAMGaddisNCChoiJDMalimMH 2002 Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 418 646 650

3. ZhangHYangBPomerantzRJZhangCArunachalamSC 2003 The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA. Nature 424 94 98

4. MangeatBTurelliPCaronGFriedliMPerrinL 2003 Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature 424 99 103

5. LecossierDBouchonnetFClavelFHanceAJ 2003 Hypermutation of HIV-1 DNA in the absence of the Vif protein. Science 300 1112

6. HarrisRSBishopKNSheehyAMCraigHMPetersen-MahrtSK 2003 DNA deamination mediates innate immunity to retroviral infection. Cell 113 803 809

7. BishopKNVermaMKimEYWolinskySMMalimMH 2008 APOBEC3G inhibits elongation of HIV-1 reverse transcripts. PLoS Pathog 4 e1000231

8. NewmanENHolmesRKCraigHMKleinKCLingappaJR 2005 Antiviral function of APOBEC3G can be dissociated from cytidine deaminase activity. Curr Biol 15 166 170

9. KaoSKhanMAMiyagiEPlishkaRBuckler-WhiteA 2003 The human immunodeficiency virus type 1 Vif protein reduces intracellular expression and inhibits packaging of APOBEC3G (CEM15), a cellular inhibitor of virus infectivity. J Virol 77 11398 11407

10. MehleAStrackBAncutaPZhangCMcPikeM 2004 Vif overcomes the innate antiviral activity of APOBEC3G by promoting its degradation in the ubiquitin-proteasome pathway. J Biol Chem 279 7792 7798

11. MehleAGoncalvesJSanta-MartaMMcPikeMGabuzdaD 2004 Phosphorylation of a novel SOCS-box regulates assembly of the HIV-1 Vif-Cul5 complex that promotes APOBEC3G degradation. Genes Dev 18 2861 2866

12. YuXYuYLiuBLuoKKongW 2003 Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex. Science 302 1056 1060

13. MarinMRoseKMKozakSLKabatD 2003 HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation. Nat Med 9 1398 1403

14. ConticelloSGHarrisRSNeubergerMS 2003 The Vif protein of HIV triggers degradation of the human antiretroviral DNA deaminase APOBEC3G. Curr Biol 13 2009 2013

15. BergeronJRHuthoffHVeselkovDABeavilRLSimpsonPJ 2010 The SOCS-box of HIV-1 Vif interacts with ElonginBC by induced-folding to recruit its Cul5-containing ubiquitin ligase complex. PLoS Pathog 6 e1000925

16. ShirakawaKTakaori-KondoAKobayashiMTomonagaMIzumiT 2006 Ubiquitination of APOBEC3 proteins by the Vif-Cullin5-ElonginB-ElonginC complex. Virology 344 263 266

17. SheehyAMGaddisNCMalimMH 2003 The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif. Nat Med 9 1404 1407

18. RulliSJJrMirroJHillSALloydPGorelickRJ 2008 Interactions of murine APOBEC3 and human APOBEC3G with murine leukemia viruses. J Virol 82 6566 6575

19. BogerdHPTallmadgeRLOaksJLCarpenterSCullenBR 2008 Equine infectious anemia virus resists the antiretroviral activity of equine APOBEC3 proteins through a packaging-independent mechanism. J Virol 82 11889 11901

20. OhsugiTKoitoA 2007 Human T cell leukemia virus type I is resistant to the antiviral effects of APOBEC3. J Virol Methods 139 93 96

21. DoehleBPSchaferAWiegandHLBogerdHPCullenBR 2005 Differential sensitivity of murine leukemia virus to APOBEC3-mediated inhibition is governed by virion exclusion. J Virol 79 8201 8207

22. Goila-GaurRKhanMAMiyagiEKaoSOpiS 2008 HIV-1 Vif promotes the formation of high molecular mass APOBEC3G complexes. Virology 372 136 146

23. KaoSMiyagiEKhanMATakeuchiHOpiS 2004 Production of infectious human immunodeficiency virus type 1 does not require depletion of APOBEC3G from virus-producing cells. Retrovirology 1 27

24. PionMGranelli-PipernoAMangeatBStalderRCorreaR 2006 APOBEC3G/3F mediates intrinsic resistance of monocyte-derived dendritic cells to HIV-1 infection. J Exp Med 203 2887 2893

25. KamataMNagaokaYChenIS 2009 Reassessing the role of APOBEC3G in human immunodeficiency virus type 1 infection of quiescent CD4+ T-cells. PLoS Pathog 5 e1000342

26. DettenhoferMYuXF 1999 Highly purified human immunodeficiency virus type 1 reveals a virtual absence of Vif in virions. J Virol 73 1460 1467

27. SimonJHMillerDLFouchierRAMalimMH 1998 Virion incorporation of human immunodeficiency virus type-1 Vif is determined by intracellular expression level and may not be necessary for function. Virology 248 182 187

28. MalimMH 2009 APOBEC proteins and intrinsic resistance to HIV-1 infection. Philos Trans R Soc Lond B Biol Sci 364 675 687

29. ChiuYLGreeneWC 2008 The APOBEC3 cytidine deaminases: an innate defensive network opposing exogenous retroviruses and endogenous retroelements. Annu Rev Immunol 26 317 353

30. OhAinleMKernsJALiMMMalikHSEmermanM 2008 Antiretroelement activity of APOBEC3H was lost twice in recent human evolution. Cell Host Microbe 4 249 259

31. BishopKNHolmesRKSheehyAMDavidsonNOChoSJ 2004 Cytidine deamination of retroviral DNA by diverse APOBEC proteins. Curr Biol 14 1392 1396

32. LandrySNarvaizaILinfestyDCWeitzmanMD 2011 APOBEC3A can activate the DNA damage response and cause cell-cycle arrest. EMBO Rep 12 444 50

33. ThielenBKMcNevinJPMcElrathMJHuntBVKleinKC 2010 Innate immune signaling induces high levels of TC-specific deaminase activity in primary monocyte-derived cells through expression of APOBEC3A isoforms. J Biol Chem 285 27753 27766

34. SuspeneRAynaudMMGuetardDHenryMEckhoffG 2011 Somatic hypermutation of human mitochondrial and nuclear DNA by APOBEC3 cytidine deaminases, a pathway for DNA catabolism. Proc Natl Acad Sci U S A 108 4858 4863

35. StengleinMDBurnsMBLiMLengyelJHarrisRS 2010 APOBEC3 proteins mediate the clearance of foreign DNA from human cells. Nat Struct Mol Biol 17 222 229

36. ChenHLilleyCEYuQLeeDVChouJ 2006 APOBEC3A is a potent inhibitor of adeno-associated virus and retrotransposons. Curr Biol 16 480 485

37. BogerdHPWiegandHLHulmeAEGarcia-PerezJLO'SheaKS 2006 Cellular inhibitors of long interspersed element 1 and Alu retrotransposition. Proc Natl Acad Sci U S A 103 8780 8785

38. BogerdHPWiegandHLDoehleBPLuedersKKCullenBR 2006 APOBEC3A and APOBEC3B are potent inhibitors of LTR-retrotransposon function in human cells. Nucleic Acids Res 34 89 95

39. MuckenfussHHamdorfMHeldUPerkovicMLowerJ 2006 APOBEC3 proteins inhibit human LINE-1 retrotransposition. J Biol Chem 281 22161 22172

40. WiegandHLCullenBR 2007 Inhibition of alpharetrovirus replication by a range of human APOBEC3 proteins. J Virol 81 13694 13699

41. VartanianJPGuetardDHenryMWain-HobsonS 2008 Evidence for editing of human papillomavirus DNA by APOBEC3 in benign and precancerous lesions. Science 320 230 233

42. PengGGreenwell-WildTNaresSJinWLeiKJ 2007 Myeloid differentiation and susceptibility to HIV-1 are linked to APOBEC3 expression. Blood 110 393 400

43. KoningFANewmanENKimEYKunstmanKJWolinskySM 2009 Defining APOBEC3 expression patterns in human tissues and hematopoietic cell subsets. J Virol 83 9474 9485

44. RefslandEWStengleinMDShindoKAlbinJSBrownWL 2010 Quantitative profiling of the full APOBEC3 mRNA repertoire in lymphocytes and tissues: implications for HIV-1 restriction. Nucleic Acids Res 38 4274 4284

45. HeathWRCarboneFR 2009 Dendritic cell subsets in primary and secondary T cell responses at body surfaces. Nat Immunol 10 1237 1244

46. PiguetVSteinmanRM 2007 The interaction of HIV with dendritic cells: outcomes and pathways. Trends Immunol 28 503 510

47. MartinezFOSicaAMantovaniALocatiM 2008 Macrophage activation and polarization. Front Biosci 13 453 461

48. ArfiVLienardJNguyenXNBergerGRigalD 2009 Characterization of the behavior of functional viral genomes during the early steps of human immunodeficiency virus type 1 infection. J Virol 83 7524 7535

49. ArfiVRiviereLJarrosson-WuillemeLGoujonCRigalD 2008 Characterization of the early steps of infection of primary blood monocytes by human immunodeficiency virus type 1. J Virol 82 6557 6565

50. GoujonCRiviereLJarrosson-WuillemeLBernaudJRigalD 2007 SIVSM/HIV-2 Vpx proteins promote retroviral escape from a proteasome-dependent restriction pathway present in human dendritic cells. Retrovirology 4 2

51. TriquesKStevensonM 2004 Characterization of restrictions to human immunodeficiency virus type 1 infection of monocytes. J Virol 78 5523 5527

52. SonzaSMaerzADeaconNMeangerJMillsJ 1996 Human immunodeficiency virus type 1 replication is blocked prior to reverse transcription and integration in freshly isolated peripheral blood monocytes. J Virol 70 3863 3869

53. O'BrienWANamaziAKalhorHMaoSHZackJA 1994 Kinetics of human immunodeficiency virus type 1 reverse transcription in blood mononuclear phagocytes are slowed by limitations of nucleotide precursors. J Virol 68 1258 1263

54. NeilSMartinFIkedaYCollinsM 2001 Postentry restriction to human immunodeficiency virus-based vector transduction in human monocytes. J Virol 75 5448 5456

55. CollinMGordonS 1994 The kinetics of human immunodeficiency virus reverse transcription are slower in primary human macrophages than in a lymphoid cell line. Virology 200 114 120

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

57. LafuseWPBrownDCastleLZwillingBS 1995 Cloning and characterization of a novel cDNA that is IFN-gamma-induced in mouse peritoneal macrophages and encodes a putative GTP-binding protein. J Leukoc Biol 57 477 483

58. RiceGIBondJAsipuABrunetteRLManfieldIW 2009 Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response. Nat Genet 41 829 832

59. HreckaKHaoCGierszewskaMSwansonSKKesik-BrodackaM 2011 Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein. Nature 474 658 661

60. LaguetteNSobhianBCasartelliNRingeardMChable-BessiaC 2011 SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature 474 654 657

61. RoseJMCrowleyCKFleischmannWRJr 1985 Evidence that IFN-alph/beta induces two antiviral states active against different viruses. J Gen Virol 66 Pt 5 1153 1158

62. FamillettiPCRubinsteinSPestkaS 1981 A convenient and rapid cytopathic effect inhibition assay for interferon. Methods Enzymol 78 387 394

63. HarmanANLaiJTurvilleSSamarajiwaSGrayL 2011 HIV infection of dendritic cells subverts the interferon induction pathway via IRF1 and inhibits type 1 interferon production. Blood 118 298 308

64. PengGLeiKJJinWGreenwell-WildTWahlSM 2006 Induction of APOBEC3 family proteins, a defensive maneuver underlying interferon-induced anti-HIV-1 activity. J Exp Med 203 41 46

65. BonvinMAchermannFGreeveIStrokaDKeoghA 2006 Interferon-inducible expression of APOBEC3 editing enzymes in human hepatocytes and inhibition of hepatitis B virus replication. Hepatology 43 1364 1374

66. GoujonCJarrosson-WuillemeLBernaudJRigalDDarlixJL 2003 Heterologous human immunodeficiency virus type 1 lentiviral vectors packaging a simian immunodeficiency virus-derived genome display a specific postentry transduction defect in dendritic cells. J Virol 77 9295 9304

67. GoujonCArfiVPertelTLubanJLienardJ 2008 Characterization of simian immunodeficiency virus SIVSM/human immunodeficiency virus type 2 Vpx function in human myeloid cells. J Virol 82 12335 12345

68. ThomasJAOttDEGorelickRJ 2007 Efficiency of human immunodeficiency virus type 1 postentry infection processes: evidence against disproportionate numbers of defective virions. J Virol 81 4367 4370

69. 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

70. 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

71. KaushikRZhuXStranskaRWuYStevensonM 2009 A cellular restriction dictates the permissivity of nondividing monocytes/macrophages to lentivirus and gammaretrovirus infection. Cell Host Microbe 6 68 80

72. BergerAMunkCSchweizerMCichutekKSchuleS 2010 Interaction of Vpx and apolipoprotein B mRNA-editing catalytic polypeptide 3 family member A (APOBEC3A) correlates with efficient lentivirus infection of monocytes. J Biol Chem 285 12248 12254

73. WenXDuusKMFriedrichTDde NoronhaCM 2007 The HIV1 protein Vpr acts to promote G2 cell cycle arrest by engaging a DDB1 and Cullin4A-containing ubiquitin ligase complex using VprBP/DCAF1 as an adaptor. J Biol Chem 282 27046 27057

74. McCallCMMiliani de MarvalPLChastainPD2ndJacksonSCHeYJ 2008 Human immunodeficiency virus type 1 Vpr-binding protein VprBP, a WD40 protein associated with the DDB1-CUL4 E3 ubiquitin ligase, is essential for DNA replication and embryonic development. Mol Cell Biol 28 5621 5633

75. TanLEhrlichEYuXF 2007 DDB1 and Cul4A are required for human immunodeficiency virus type 1 Vpr-induced G2 arrest. J Virol 81 10822 10830

76. Le RouzicEBelaidouniNEstrabaudEMorelMRainJC 2007 HIV1 Vpr arrests the cell cycle by recruiting DCAF1/VprBP, a receptor of the Cul4-DDB1 ubiquitin ligase. Cell Cycle 6 182 188

77. HreckaKGierszewskaMSrivastavaSKozaczkiewiczLSwansonSK 2007 Lentiviral Vpr usurps Cul4-DDB1[VprBP] E3 ubiquitin ligase to modulate cell cycle. Proc Natl Acad Sci U S A 104 11778 11783

78. BelzileJPDuisitGRougeauNMercierJFinziA 2007 HIV-1 Vpr-mediated G2 arrest involves the DDB1-CUL4AVPRBP E3 ubiquitin ligase. PLoS Pathog 3 e85

79. ThielenBKKleinKCWalkerLWRieckMBucknerJH 2007 T cells contain an RNase-insensitive inhibitor of APOBEC3G deaminase activity. PLoS Pathog 3 1320 1334

80. BulliardYNarvaizaIBerteroAPeddiSRohrigUF 2011 Structure-function analyses point to a polynucleotide-accommodating groove essential for APOBEC3A restriction activities. J Virol 85 1765 1776

81. GoujonCJarrosson-WuillemeLBernaudJRigalDDarlixJL 2006 With a little help from a friend: increasing HIV transduction of monocyte-derived dendritic cells with virion-like particles of SIV(MAC). Gene Ther 13 991 994