Role of Exonic Variation in Chemokine Receptor Genes on AIDS: Association with Pneumocystis Pneumonia

English version České info

Chromosome 3p21–22 harbors two clusters of chemokine receptor genes, several of which serve as major or minor coreceptors of HIV-1. Although the genetic association of CCR5 and CCR2 variants with HIV-1 pathogenesis is well known, the role of variation in other nearby chemokine receptor genes remain unresolved. We genotyped exonic single nucleotide polymorphisms (SNPs) in chemokine receptor genes: CCR3, CCRL2, and CXCR6 (at 3p21) and CCR8 and CX3CR1 (at 3p22), the majority of which were non-synonymous. The individual SNPs were tested for their effects on disease progression and outcomes in five treatment-naïve HIV-1/AIDS natural history cohorts. In addition to the known CCR5 and CCR2 associations, significant associations were identified for CCR3, CCR8, and CCRL2 on progression to AIDS. A multivariate survival analysis pointed to a previously undetected association of a non-conservative amino acid change F167Y in CCRL2 with AIDS progression: 167F is associated with accelerated progression to AIDS (RH = 1.90, P = 0.002, corrected). Further analysis indicated that CCRL2-167F was specifically associated with more rapid development of pneumocystis pneumonia (PCP) (RH = 2.84, 95% CI 1.28–6.31) among four major AIDS–defining conditions. Considering the newly defined role of CCRL2 in lung dendritic cell trafficking, this atypical chemokine receptor may affect PCP through immune regulation and inducing inflammation.

Vyšlo v časopise: Role of Exonic Variation in Chemokine Receptor Genes on AIDS: Association with Pneumocystis Pneumonia. PLoS Genet 7(10): e32767. doi:10.1371/journal.pgen.1002328
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002328

Souhrn

Zdroje

1. CarringtonMNelsonGWMartinMPKissnerTVlahovD 1999 HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage. Science 283 1748 1752

2. O'BrienSJNelsonGW 2004 Human genes that limit AIDS. Nat Genet 36 565 574

3. FellayJShiannaKVGeDColomboSLedergerberB 2007 A whole-genome association study of major determinants for host control of HIV-1. Science 317 944 947

4. AnPWinklerCA 2010 Host genes associated with HIV/AIDS: advances in gene discovery. Trends Genet 26 119 131

5. FellayJGeDShiannaKVColomboSLedergerberB 2009 Common genetic variation and the control of HIV-1 in humans. PLoS Genet 5 e1000791 doi:10.1371/journal.pgen.1000791

6. LimouSLe ClercSCoulongesCCarpentierWDinaC 2009 Genomewide association study of an AIDS-nonprogression cohort emphasizes the role played by HLA genes (ANRS Genomewide Association Study 02). J Infect Dis 199 419 426

7. HerbeckJTGottliebGSWinklerCANelsonGWAnP 2010 Multistage genomewide association study identifies a locus at 1q41 associated with rate of HIV-1 disease progression to clinical AIDS. J Infect Dis 201 618 626

8. PereyraFJiaXMcLarenPJTelentiAde BakkerPI 2010 The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science 330 1551 1557

9. DengHLiuREllmeierWChoeSUnutmazD 1996 Identification of a major co-receptor for primary isolates of HIV-1. Nature 381 661 666

10. AlkhatibGCombadiereCBroderCCFengYKennedyPE 1996 CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science 272 1955 1958

11. BergerEAMurphyPMFarberJM 1999 Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu Rev Immunol 17 657 700

12. IoannidisJPRosenbergPSGoedertJJAshtonLJBenfieldTL 2001 Effects of CCR5-Delta32, CCR2-64I, and SDF-1 3′A alleles on HIV-1 disease progression: An international meta-analysis of individual-patient data. Ann Intern Med 135 782 795

13. O'BrienSJMooreJP 2000 The effect of genetic variation in chemokines and their receptors on HIV transmission and progression to AIDS. Immunol Rev 177 99 111

14. DeanMCarringtonMWinklerCHuttleyGASmithMW 1996 Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science 273 1856 1862

15. MartinMPDeanMSmithMWWinklerCGerrardB 1998 Genetic acceleration of AIDS progression by a promoter variant of CCR5. Science 282 1907 1911

16. McDermottDHZimmermanPAGuignardFKleebergerCALeitmanSF 1998 CCR5 promoter polymorphism and HIV-1 disease progression. Multicenter AIDS Cohort Study (MACS). Lancet 352 866 870

17. AnPMartinMPNelsonGWCarringtonMSmithMW 2000 Influence of CCR5 promoter haplotypes on AIDS progression in African-Americans. AIDS 14 2117 2122

18. LiuHChaoDNakayamaEETaguchiHGotoM 1999 Polymorphism in RANTES chemokine promoter affects HIV-1 disease progression. Proc Natl Acad Sci U S A 96 4581 4585

19. AnPNelsonGWWangLDonfieldSGoedertJJ 2002 Modulating influence on HIV/AIDS by interacting RANTES gene variants. Proc Natl Acad Sci U S A 99 10002 10007

20. HuangYPaxtonWAWolinskySMNeumannAUZhangL 1996 The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med 2 1240 1243

21. SamsonMLibertFDoranzBJRuckerJLiesnardC 1996 Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 382 722 725

22. LiuRPaxtonWAChoeSCeradiniDMartinSR 1996 Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 86 367 377

23. GonzalezEBamshadMSatoNMummidiSDhandaR 1999 Race-specific HIV-1 disease-modifying effects associated with CCR5 haplotypes. Proc Natl Acad Sci U S A 96 12004 12009

24. WinklerCAHendelHCarringtonMSmithMWNelsonGW 2004 Dominant effects of CCR2-CCR5 haplotypes in HIV-1 disease progression. J Acquir Immune Defic Syndr 37 1534 1538

25. KostrikisLGNeumannAUThomsonBKorberBTMcHardyP 1999 A polymorphism in the regulatory region of the CC-chemokine receptor 5 gene influences perinatal transmission of human immunodeficiency virus type 1 to African-American infants. J Virol 73 10264 10271

26. RuckerJEdingerALSharronMSamsonMLeeB 1997 Utilization of chemokine receptors, orphan receptors, and herpesvirus-encoded receptors by diverse human and simian immunodeficiency viruses. J Virol 71 8999 9007

27. AlkhatibGLiaoFBergerEAFarberJMPedenKW 1997 A new SIV co-receptor, STRL33. Nature 388 238

28. SmithMWDeanMCarringtonMWinklerCHuttleyGA 1997 Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study. Science 277 959 965

29. MummidiSAhujaSSGonzalezEAndersonSASantiagoEN 1998 Genealogy of the CCR5 locus and chemokine system gene variants associated with altered rates of HIV-1 disease progression. Nat Med 4 786 793

30. DuggalPAnPBeatyTHStrathdeeSAFarzadeganH 2003 Genetic influence of CXCR6 chemokine receptor alleles on PCP-mediated AIDS progression among African Americans. Genes Immun 4 245 250

31. LimouSCoulongesCHerbeckJTvan ManenDAnP 2010 Multiple-cohort genetic association study reveals CXCR6 as a new chemokine receptor involved in long-term nonprogression to AIDS. J Infect Dis 202 908 915

32. DaughertyBLSpringerMS 1997 The beta-chemokine receptor genes CCR1 (CMKBR1), CCR2 (CMKBR2), and CCR3 (CMKBR3) cluster within 285 kb on human chromosome 3p21. Genomics 41 294 295

33. ChoeHFarzanMSunYSullivanNRollinsB 1996 The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell 85 1135 1148

34. ChoeHFarzanMKonkelMMartinKSunY 1998 The orphan seven-transmembrane receptor apj supports the entry of primary T-cell-line-tropic and dualtropic human immunodeficiency virus type 1. J Virol 72 6113 6118

35. ScarlattiGTresoldiEBjorndalAFredrikssonRColognesiC 1997 In vivo evolution of HIV-1 co-receptor usage and sensitivity to chemokine-mediated suppression. Nat Med 3 1259 1265

36. NedellecRCoetzerMShimizuNHoshinoHPolonisVR 2009 Virus entry via the alternative coreceptors CCR3 and FPRL1 differs by human immunodeficiency virus type 1 subtype. J Virol 83 8353 8363

37. LussoP 2006 HIV and the chemokine system: 10 years later. EMBO J 25 447 456

38. XiaoLRudolphDLOwenSMSpiraTJLalRB 1998 Adaptation to promiscuous usage of CC and CXC-chemokine coreceptors in vivo correlates with HIV-1 disease progression. AIDS 12 F137 143

39. ConnorRISheridanKECeradiniDChoeSLandauNR 1997 Change in coreceptor use coreceptor use correlates with disease progression in HIV-1-infected individuals. J Exp Med 185 621 628

40. ShimizuNTanakaAOueAMoriTOhtsukiT 2009 Broad usage spectrum of G protein-coupled receptors as coreceptors by primary isolates of HIV. AIDS 23 761 769

41. GorryPRDunfeeRLMeffordMEKunstmanKMorganT 2007 Changes in the V3 region of gp120 contribute to unusually broad coreceptor usage of an HIV-1 isolate from a CCR5 Delta32 heterozygote. Virology 362 163 178

42. CilliersTWilleySSullivanWMPatienceTPugachP 2005 Use of alternate coreceptors on primary cells by two HIV-1 isolates. Virology 339 136 144

43. CarringtonMDeanMMartinMPO'BrienSJ 1999 Genetics of HIV-1 infection: chemokine receptor CCR5 polymorphism and its consequences. Hum Mol Genet 8 1939 1945

44. HendelHWinklerCAnPRoemer-BinnsENelsonG 2001 Validation of genetic case-control studies in AIDS and application to the CX3CR1 polymorphism. J Acquir Immune Defic Syndr 26 507 511

45. ThomsonGBarcellosLFValdesAM 2008 Searching for additional disease loci in a genomic region. Adv Genet 60 253 292

46. CordellHJClaytonDG 2002 A unified stepwise regression procedure for evaluating the relative effects of polymorphisms within a gene using case/control or family data: application to HLA in type 1 diabetes. Am J Hum Genet 70 124 141

47. HolmS 1979 A Simple Sequentially Rejective Bonferroni Test Procedure. Scand J Stat 6 65 70

48. HarrellFEJrLeeKLMarkDB 1996 Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med 15 361 387

49. YoshimuraTOppenheimJJ 2008 Chemerin reveals its chimeric nature. J Exp Med 205 2187 2190

50. AraiMMitsukeHIkedaMXiaJXKikuchiT 2004 ConPred II: a consensus prediction method for obtaining transmembrane topology models with high reliability. Nucleic Acids Res 32 W390 393

51. LeickMCatusseJFolloMNibbsRJHartmannTN 2009 CCL19 is a specific ligand of the constitutively recycling atypical human chemokine receptor CRAM-B. Immunology 129 536 546

52. ZabelBANakaeSZunigaLKimJYOhyamaT 2008 Mast cell-expressed orphan receptor CCRL2 binds chemerin and is required for optimal induction of IgE-mediated passive cutaneous anaphylaxis. J Exp Med 205 2207 2220

53. LeeSTiffanyHLKingLMurphyPMGoldingH 2000 CCR8 on human thymocytes functions as a human immunodeficiency virus type 1 coreceptor. J Virol 74 6946 6952

54. GalliganCLMatsuyamaWMatsukawaAMizutaHHodgeDR 2004 Up-regulated expression and activation of the orphan chemokine receptor, CCRL2, in rheumatoid arthritis. Arthritis Rheum 50 1806 1814

55. ThomasCFJrLimperAH 2004 Pneumocystis Pneumonia. N Engl J Med 350 2487 2498

56. HartmannTNLeickMEwersSDiefenbacherASchraufstatterI 2008 Human B cells express the orphan chemokine receptor CRAM-A/B in a maturation-stage-dependent and CCL5-modulated manner. Immunology 125 252 262

57. OostendorpJHylkemaMNLuingeMGeerlingsMMeursH 2004 Localization and enhanced mRNA expression of the orphan chemokine receptor L-CCR in the lung in a murine model of ovalbumin-induced airway inflammation. J Histochem Cytochem 52 401 410

58. OteroKVecchiAHirschEKearleyJVermiW 2010 Non-redundant role of CCRL2 in lung dendritic cell trafficking. Blood 116 2942 2949

59. PhairJJacobsonLDetelsRRinaldoCSaahA 1992 Acquired immune deficiency syndrome occurring within 5 years of infection with human immunodeficiency virus type-1: the Multicenter AIDS Cohort Study. J Acquir Immune Defic Syndr 5 490 496

60. BuchbinderSPKatzMHHessolNAO'MalleyPMHolmbergSD 1994 Long-term HIV-1 infection without immunologic progression. AIDS 8 1123 1128

61. VlahovDGrahamNHooverDFlynnCBartlettJG 1998 Prognostic indicators for AIDS and infectious disease death in HIV-infected injection drug users: plasma viral load and CD4+ cell count. JAMA 279 35 40

62. HilgartnerMWDonfieldSMWilloughbyAContantCFJrEvattBL 1993 Hemophilia growth and development study. Design, methods, and entry data. Am J Pediatr Hematol Oncol 15 208 218

63. GoedertJJKesslerCMAledortLMBiggarRJAndesWA 1989 A prospective study of human immunodeficiency virus type 1 infection and the development of AIDS in subjects with hemophilia. N Engl J Med 321 1141 1148

64. CelentanoDDVlahovDCohnSShadleVMObasanjoO 1998 Self-reported antiretroviral therapy in injection drug users. JAMA 280 544 546

65. FaureSMeyerLCostagliolaDVaneensbergheCGeninE 2000 Rapid progression to AIDS in HIV+ individuals with a structural variant of the chemokine receptor CX3CR1. Science 287 2274 2277

66. Centers for Disease Control 1987 Revision of the CDC surveillance case definition for acquired immunodeficiency syndrome. Council of State and Territorial Epidemiologists; AIDS Program, Center for Infectious Diseases. MMWR Morb Mortal Wkly Rep 36 Suppl 1 1S 15S

67. KaslowRACarringtonMAppleRParkLMunozA 1996 Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nat Med 2 405 411

68. GaoXNelsonGWKarackiPMartinMPPhairJ 2001 Effect of a single amino acid change in MHC class I molecules on the rate of progression to AIDS. N Engl J Med 344 1668 1675

69. ShtatlandESKleinmanKCainEM 2005 Model Building in PROC PHREG with Automatic Variable Selection and Information Criteria. 1 10 Proceedings of the 30th Annual SAS Users Group International Conference Paper 206-30

70. PriceALPattersonNJPlengeRMWeinblattMEShadickNA 2006 Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38 904 909

71. TroyerJLNelsonGWLautenbergerJAChinnLMcIntoshC 2011 Genome-wide association study implicates PARD3B-based AIDS restriction. J Infect Dis 203 1491 1502

72. AllisonPD 1995 Survival Analysis Using the SAS System: A Practical Guide Cary, NC SAS Institute Inc

73. LewontinRC 1964 The Interaction of Selection and Linkage. II. Optimum Models. Genetics 50 757 782

74. HungLHNganSCLiuTSamudralaR 2005 PROTINFO: new algorithms for enhanced protein structure predictions. Nucleic Acids Res 33 W77 80

75. HungLHSamudralaR 2003 PROTINFO: Secondary and tertiary protein structure prediction. Nucleic Acids Res 31 3296 3299