SAMHD1-Deficient CD14+ Cells from Individuals with Aicardi-Goutières Syndrome Are Highly Susceptible to HIV-1 Infection

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Myeloid blood cells are largely resistant to infection with human immunodeficiency virus type 1 (HIV-1). Recently, it was reported that Vpx from HIV-2/SIVsm facilitates infection of these cells by counteracting the host restriction factor SAMHD1. Here, we independently confirmed that Vpx interacts with SAMHD1 and targets it for ubiquitin-mediated degradation. We found that Vpx-mediated SAMHD1 degradation rendered primary monocytes highly susceptible to HIV-1 infection; Vpx with a T17A mutation, defective for SAMHD1 binding and degradation, did not show this activity. Several single nucleotide polymorphisms in the SAMHD1 gene have been associated with Aicardi-Goutières syndrome (AGS), a very rare and severe autoimmune disease. Primary peripheral blood mononuclear cells (PBMC) from AGS patients homozygous for a nonsense mutation in SAMHD1 (R164X) lacked endogenous SAMHD1 expression and support HIV-1 replication in the absence of exogenous activation. Our results indicate that within PBMC from AGS patients, CD14+ cells were the subpopulation susceptible to HIV-1 infection, whereas cells from healthy donors did not support infection. The monocytic lineage of the infected SAMHD1 -/- cells, in conjunction with mostly undetectable levels of cytokines, chemokines and type I interferon measured prior to infection, indicate that aberrant cellular activation is not the cause for the observed phenotype. Taken together, we propose that SAMHD1 protects primary CD14+ monocytes from HIV-1 infection confirming SAMHD1 as a potent lentiviral restriction factor.

Vyšlo v časopise: SAMHD1-Deficient CD14+ Cells from Individuals with Aicardi-Goutières Syndrome Are Highly Susceptible to HIV-1 Infection. PLoS Pathog 7(12): e32767. doi:10.1371/journal.ppat.1002425
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002425

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1. 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

2. NeilSMartinFIkedaYCollinsM 2001 Postentry restriction to human immunodeficiency virus-based vector transduction in human monocytes. J Virol 75 5448 5456 10.1128/JVI.75.12.5448-5456.2001 [doi]

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

4. NegreDMangeotPEDuisitGBlanchardSVidalainPO 2000 Characterization of novel safe lentiviral vectors derived from simian immunodeficiency virus (SIVmac251) that efficiently transduce mature human dendritic cells. Gene Ther 7 1613 1623 10.1038/sj.gt.3301292 [doi]

5. FujitaMOtsukaMNomaguchiMAdachiA 2010 Multifaceted activity of HIV Vpr/Vpx proteins: the current view of their virological functions. Rev Med Virol 20 68 76

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

7. YuXFYuQCEssexMLeeTH 1991 The vpx gene of simian immunodeficiency virus facilitates efficient viral replication in fresh lymphocytes and macrophage. J Virol 65 5088 5091

8. HirschVMSharkeyMEBrownCRBrichacekBGoldsteinS 1998 Vpx is required for dissemination and pathogenesis of SIV(SM) PBj: evidence of macrophage-dependent viral amplification. Nat Med 4 1401 1408

9. 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

10. SchuleSKlokeBPKaiserJKHeidmeierSPanitzS 2009 Restriction of HIV-1 replication in monocytes is abolished by Vpx of SIVsmmPBj. PLoS One 4 e7098

11. 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

12. GrambergTSunseriNLandauNR 2010 Evidence for an activation domain at the amino terminus of simian immunodeficiency virus Vpx. J Virol 84 1387 1396

13. AccolaMABukovskyAAJonesMSGottlingerHG 1999 A conserved dileucine-containing motif in p6(gag) governs the particle association of Vpx and Vpr of simian immunodeficiency viruses SIV(mac) and SIV(agm). J Virol 73 9992 9999

14. StrebelKLubanJJeangKT 2009 Human cellular restriction factors that target HIV-1 replication. BMC Med 7 48. 1741-7015-7-48 [pii];10.1186/1741-7015-7-48 [doi]

15. WolfDGoffSP 2008 Host restriction factors blocking retroviral replication. Annu Rev Genet 42 143 163 10.1146/annurev.genet.42.110807.091704 [doi]

16. 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

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

18. 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

19. HreckaKHaoCGierszewskaMSwansonSKKesik-BrodackaM 2011 Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein. Nature 474 658 661 nature10195 [pii];10.1038/nature10195 [doi]

20. LaguetteNSobhianBCasartelliNRingeardMChable-BessiaC 2011 SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature 474 654 657 nature10117 [pii];10.1038/nature10117 [doi]

21. CrowYJLivingstonJH 2008 Aicardi-Goutieres syndrome: an important Mendelian mimic of congenital infection. Dev Med Child Neurol 50 410 416 DMCN02062 [pii];10.1111/j.1469-8749.2008.02062.x [doi]

22. Lee-KirschMA 2010 Nucleic acid metabolism and systemic autoimmunity revisited. Arthritis Rheum 62 1208 1212 10.1002/art.27372 [doi]

23. DussaixELebonPPonsotGHuaultGTardieuM 1985 Intrathecal synthesis of different alpha-interferons in patients with various neurological diseases. Acta Neurol Scand 71 504 509

24. YanNRegalado-MagdosADStiggelboutBLee-KirschMALiebermanJ 2010 The cytosolic exonuclease TREX1 inhibits the innate immune response to human immunodeficiency virus type 1. Nat Immunol 11 1005 1013 ni.1941 [pii];10.1038/ni.1941 [doi]

25. RiceGIBondJAsipuABrunetteRLManfieldIW 2009 Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response. Nat Genet 41 829 832 ng.373 [pii];10.1038/ng.373 [doi]

26. duMMNurnbergPCrowYJRutschF 2011 Cerebral vasculopathy is a common feature in Aicardi-Goutieres syndrome associated with SAMHD1 mutations. Proc Natl Acad Sci U S A 108 1104699108 [pii];10.1073/pnas.1104699108 [doi] e232

27. RameshVBernardiBStafaAGaroneCFranzoniE 2010 Intracerebral large artery disease in Aicardi-Goutieres syndrome implicates SAMHD1 in vascular homeostasis. Dev Med Child Neurol 52 725 732 DMCN3727 [pii];10.1111/j.1469-8749.2010.03727.x [doi]

28. ThieleHduMMBarczykKGeorgeCSchwindtW 2010 Cerebral arterial stenoses and stroke: novel features of Aicardi-Goutieres syndrome caused by the Arg164X mutation in SAMHD1 are associated with altered cytokine expression. Hum Mutat 31 E1836 E1850 10.1002/humu.21357 [doi]

29. XinBJonesSPuffenbergerEGHinzeCBrightA 2011 Homozygous mutation in SAMHD1 gene causes cerebral vasculopathy and early onset stroke. Proc Natl Acad Sci U S A 108 5372 5377 1014265108 [pii];10.1073/pnas.1014265108 [doi]

30. 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

31. WiskerchenMMuesingMA 1995 Human immunodeficiency virus type 1 integrase: effects of mutations on viral ability to integrate, direct viral gene expression from unintegrated viral DNA templates, and sustain viral propagation in primary cells. J Virol 69 376 386

32. FeinbergMBJarrettRFAldoviniAGalloRCWong-StaalF 1986 HTLV-III expression and production involve complex regulation at the levels of splicing and translation of viral RNA. Cell 46 807 817 0092-8674(86)90062-0 [pii]

33. MunozCMissetBFittingCBleriotJPCarletJ 1991 Dissociation between plasma and monocyte-associated cytokines during sepsis. Eur J Immunol 21 2177 2184 10.1002/eji.1830210928 [doi]

34. de BontESKimpenJLTammingaRYNiemarktAEde LeijLH 2000 Intrinsic capacity of monocytes to produce cytokines ex vivo in patients with acute lymphoblastic leukaemia. Cytokine 12 1723 1726 10.1006/cyto.2000.0776 [doi];S1043-4666(00)90776-2 [pii]

35. KaiserSERileyBEShalerTATrevinoRSBeckerCH 2011 Protein standard absolute quantification (PSAQ) method for the measurement of cellular ubiquitin pools. Nat Methods 8 691 696 nmeth.1649 [pii];10.1038/nmeth.1649 [doi]

36. QiaoFBowieJU 2005 The many faces of SAM. Sci STKE 2005:re7. stke.2862005re7 [pii];10.1126/stke.2862005re7 [doi]

37. OberstrassFCLeeASteflRJanisMChanfreauG 2006 Shape-specific recognition in the structure of the Vts1p SAM domain with RNA. Nat Struct Mol Biol 13 160 167 nsmb1038 [pii];10.1038/nsmb1038 [doi]

38. ZimmermanMDProudfootMYakuninAMinorW 2008 Structural insight into the mechanism of substrate specificity and catalytic activity of an HD-domain phosphohydrolase: the 5′-deoxyribonucleotidase YfbR from Escherichia coli. J Mol Biol 378 215 226 S0022-2836(08)00233-7 [pii];10.1016/j.jmb.2008.02.036 [doi]

39. AravindLKooninEV 1998 The HD domain defines a new superfamily of metal-dependent phosphohydrolases. Trends Biochem Sci 23 469 472 S0968-0004(98)01293-6 [pii]

40. OussenkoIASanchezRBechhoferDH 2002 Bacillus subtilis YhaM, a member of a new family of 3′-to-5′ exonucleases in gram-positive bacteria. J Bacteriol 184 6250 6259

41. NeilSBieniaszP 2009 Human immunodeficiency virus, restriction factors, and interferon. J Interferon Cytokine Res 29 569 580 10.1089/jir.2009.0077 [doi]

42. UchilPDQuinlanBDChanWTLunaJMMothesW 2008 TRIM E3 ligases interfere with early and late stages of the retroviral life cycle. PLoS Pathog 4 07-PLPA-RA-0403 [pii];10.1371/journal.ppat.0040016 [doi] e16

43. BergerGDurandSFargierGNguyenXNCordeilS 2011 APOBEC3A Is a Specific Inhibitor of the Early Phases of HIV-1 Infection in Myeloid Cells. PLoS Pathog 7 e1002221

44. ArhelN 2010 Revisiting HIV-1 uncoating. Retrovirology 7 96. 1742-4690-7-96 [pii];10.1186/1742-4690-7-96 [doi]

45. ConnorRIChenBKChoeSLandauNR 1995 Vpr is required for efficient replication of human immunodeficiency virus type-1 in mononuclear phagocytes. Virology 206 935 944 S0042-6822(85)71016-1 [pii];10.1006/viro.1995.1016 [doi]

46. Rodriguez-MadozJRBelicha-VillanuevaABernal-RubioDAshourJAyllonJ 2010 Inhibition of the type I interferon response in human dendritic cells by dengue virus infection requires a catalytically active NS2B3 complex. J Virol 84 9760 9774 JVI.01051-10 [pii];10.1128/JVI.01051-10 [doi]