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Polymorphisms in the interleukin-4 receptor α chain gene influence susceptibility to HIV-1 infection and its progression to AIDS

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Abstract

Interleukin (IL) 4 is a key T helper-2 cytokine that downregulates and upregulates CCR5 and CXCR4, respectively, the main coreceptors for HIV. Our objective is to investigate whether single-nucleotide polymorphisms (SNPs) in the IL-4 receptor α chain gene (IL4RA) affect HIV infection and its progression to AIDS. The I50V SNP in exon 5 and the haplotypes of six SNPs in exon 12 (E375A, C406R, S411L, S478P, Q551R, and V554I) were studied by polymerase chain reaction and sequencing in 30 HIV+ long-term nonprogressors (LTNP), 36 HIV+ typical progressors (TP), 55 highly exposed but uninfected individuals (EU), 25 EU-sexuals (EU-Sex; mostly women) and 30 EU-hemophiliacs (EU-Hem; hepatitis C virus+), and 97 healthy controls (HC), all Caucasians and lacking CCR5Δ32 homozygosity. V50 homozygosity was increased in LTNP (44%) compared with the other groups [p=0.005; relative risk ratio=3.4, 95% confidence interval (CI)=1.12–10.6, p=0.03]. The most common (C) exon 12 haplotype, ECSSQV, predominated in all groups, but uncommon (U) haplotypes were increased in HIV+ individuals (n=64), especially in those (51 of 64) infected via parenteral exposure (35.3%) compared with HC (20.4%) and EU-Hem (18.4%) [p=0.01; odds ratio (OR)=2.14, 95% CI=1.25–3.67, p=0.01]. EU-Sex also had an increased frequency of U-haplotypes (34.8%) (OR=2.10, 95% CI=1.03–4.21, p=0.01) as well as an increased frequency of CU + UU genotypes (60.9%) compared with HC (38.2%) and EU-Hem (26.6%) (p=0.043). Distributions of genotypes fitted Hardy–Weinberg equilibrium. Data suggest that V50 homozygosity associates with slow progression and that exon 12 U-haplotypes might be associated with both susceptibility to infection via parenteral route and resistance to infection via sexual exposure. Further studies are required to confirm these findings.

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References

  • An P, Bleiber G, Duggal P, Nelson G, May M, Mangeat B, Alobwede I, Trono D, Vlahov D, Donfield S, Goedert JJ, Phair J, Buchbinder S, O'Brien SJ, Telenti A, Winkler CA (2004) APOBEC3G genetic variants and their influence on the progression to AIDS. J Virol 78:11070–11076

    Article  PubMed  CAS  Google Scholar 

  • Berger EA, Murphy PM, Farber JM (1999) Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu Rev Immunol 17:657–700, 657–700

    Article  PubMed  CAS  Google Scholar 

  • Biasin M, Boasso A, Piacentini L, Trabattoni D, Magri G, Deshmuks R, Deshpande A, Clerici M (2003) IL-4 and CXCR4 upregulation in HIV-infected and uninfected individuals from Maharashtra–Mumbai. AIDS 17:1563–1565

    Article  PubMed  Google Scholar 

  • Bottini N, Borgiani P, Otsu A, Saccucci P, Stefanini L, Greco E, Fontana L, Hopkin JM, Mao XQ, Shirakawa T (2002) IL-4 receptor alpha chain genetic polymorphism and total IgE levels in the English population: two-locus haplotypes are more informative than individual SNPs. Clin Genet 61:288–292

    Article  PubMed  CAS  Google Scholar 

  • Clerici M, Shearer GM (1994) The Th1–Th2 hypothesis of HIV infection: new insights. Immunol. Today 15:575–581

    Article  PubMed  CAS  Google Scholar 

  • Colobran R, Adreani P, Ashhab Y, Llano A, Este JA, Dominguez O, Pujol-Borrell R, Juan M (2005) Multiple products derived from two CCL4 loci: high incidence of a new polymorphism in HIV+ patients. J Immunol 174:5655–5664

    PubMed  CAS  Google Scholar 

  • Connor RI, Sheridan KE, Ceradini D, Choe S, Landau NR (1997) Change in coreceptor use coreceptor use correlates with disease progression in HIV-1-infected individuals. J Exp Med 185:621–628

    Article  PubMed  CAS  Google Scholar 

  • Dean M, Carrington M, Winkler C, Huttley GA, Smith MW, Allikmets R, Goedert JJ, Buchbinder SP, Vittinghoff E, Gomperts E, Donfield S, Vlahov D, Kaslow R, Saah A, Rinaldo C, Detels R, O'Brien SJ (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

    Article  PubMed  CAS  Google Scholar 

  • Deichmann K, Bardutzky J, Forster J, Heinzmann A, Kuehr J (1997) Common polymorphisms in the coding part of the IL4-receptor gene. Biochem Biophys Res Commun 231:696–697

    Article  PubMed  CAS  Google Scholar 

  • Devito C, Hinkula J, Kaul R, Lopalco L, Bwayo JJ, Plummer F, Clerici M, Broliden K (2000) Mucosal and plasma IgA from HIV-exposed seronegative individuals neutralize a primary HIV-1 isolate. AIDS 14:1917–1920

    Article  PubMed  CAS  Google Scholar 

  • Dhillon NK, Sui Y, Potula R, Dhillon S, Adany I, Li Z, Villinger F, Pinson D, Narayan O, Buch S (2005) Inhibition of pathogenic SHIV replication in macaques treated with antisense DNA of interleukin-4. Blood 105:3094–3099

    Article  PubMed  CAS  Google Scholar 

  • Do H, Vasilescu A, Diop G, Hirtzig T, Heath SC, Coulonges C, Rappaport J, Therwath A, Lathrop M, Matsuda F, Zagury JF (2005) Exhaustive genotyping of the CEM15 (APOBEC3G) gene and absence of association with AIDS progression in a French cohort. J Infect Dis 191:159–163

    Article  PubMed  CAS  Google Scholar 

  • Franjkovic I, Gessner A, Konig I, Kissel K, Bohnert A, Hartung A, Ohly A, Ziegler A, Hackstein H, Bein G (2005) Effects of common atopy-associated amino acid substitutions in the IL-4 receptor alpha chain on IL-4 induced phenotypes. Immunogenetics 56:808–817

    Article  PubMed  CAS  Google Scholar 

  • Galli G, Annunziato F, Mavilia C, Romagnani P, Cosmi L, Manetti R, Pupilli C, Maggi E, Romagnani S (1998) Enhanced HIV expression during Th2-oriented responses explained by the opposite regulatory effect of IL-4 and IFN-gamma of fusin/CXCR4. Eur J Immunol 28:3280–3290

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez E, Kulkarni H, Bolivar H, Mangano A, Sanchez R, Catano G, Nibbs RJ, Freedman BI, Quinones MP, Bamshad MJ, Murthy KK, Rovin BH, Bradley W, Clark RA, Anderson SA, O'Connell RJ, Agan BK, Ahuja SS, Bologna R, Sen L, Dolan MJ, Ahuja SK (2005) The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science 307:1434–1440

    Article  PubMed  CAS  Google Scholar 

  • Hershey GK (2003) IL-13 receptors and signaling pathways: an evolving web. J Allergy Clin Immunol 111:677–690

    Article  PubMed  CAS  Google Scholar 

  • Hershey GK, Friedrich MF, Esswein LA, Thomas ML, Chatila TA (1997) The association of atopy with a gain-of-function mutation in the alpha subunit of the interleukin-4 receptor. N Engl J Med 337:1720–1725

    Article  PubMed  CAS  Google Scholar 

  • Ho IC, Glimcher LH (2002) Transcription: tantalizing times for T cells. Cell Suppl 109:S109–S120

    CAS  Google Scholar 

  • Hoffjan S, Ober C (2002) Present status on the genetic studies of asthma. Curr Opin Immunol 14:709–717

    Article  PubMed  CAS  Google Scholar 

  • Howard TD, Koppelman GH, Xu J, Zheng SL, Postma DS, Meyers DA, Bleecker ER (2002) Gene–gene interaction in asthma: IL4RA and IL13 in a Dutch population with asthma. Am J Hum Genet 70:230–236

    Article  PubMed  CAS  Google Scholar 

  • Huang Y, Paxton WA, Wolinsky SM, Neumann AU, Zhang L, He T, Kang S, Ceradini D, Jin Z, Yazdanbakhsh K, Kunstman K, Erickson D, Dragon E, Landau NR, Phair J, Ho DD, Koup RA (1996) The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med 2:1240–1243

    Article  PubMed  CAS  Google Scholar 

  • Ioannidis JP, Rosenberg PS, Goedert JJ, Ashton LJ, Benfield TL, Buchbinder SP, Coutinho RA, Eugen-Olsen J, Gallart T, Katzenstein TL, Kostrikis LG, Kuipers H, Louie LG, Mallal SA, Margolick JB, Martinez OP, Meyer L, Michael NL, Operskalski E, Pantaleo G, Rizzardi GP, Schuitemaker H, Sheppard HW, Stewart GJ, Theodorou ID, Ullum H, Vicenzi E, Vlahov D, Wilkinson D, Workman C, Zagury JF, O'Brien TR (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

    PubMed  CAS  Google Scholar 

  • Ji X, Gewurz H, Spear GT (2005) Mannose binding lectin (MBL) and HIV. Mol Immunol 42:145–152

    Article  PubMed  CAS  Google Scholar 

  • Jourdan P, Abbal C, Noraz N, Hori T, Uchiyama T, Vendrell JP, Bousquet J, Taylor N, Pene J, Yssel H (1998) IL-4 induces functional cell-surface expression of CXCR4 on human T cells 72. J Immunol 160:4153–4157

    PubMed  CAS  Google Scholar 

  • Kaslow RA, Dorak T, Tang JJ (2005) Influence of host genetic variation on susceptibility to HIV type 1 infection. J Infect Dis 191(Suppl 1):S68–S77

    Article  PubMed  Google Scholar 

  • Klein SA, Dobmeyer JM, Dobmeyer TS, Pape M, Ottmann OG, Helm EB, Hoelzer D, Rossol R (1997) Demonstration of the Th1 to Th2 cytokine shift during the course of HIV-1 infection using cytoplasmic cytokine detection on single cell level by flow cytometry. AIDS 11:1111–1118

    Article  PubMed  CAS  Google Scholar 

  • Kostrikis LG, Huang Y, Moore JP, Wolinsky SM, Zhang L, Guo Y, Deutsch L, Phair J, Neumann AU, Ho DD (1998) A chemokine receptor CCR2 allele delays HIV-1 disease progression and is associated with a CCR5 promoter mutation. Nat Med 4:350–353

    Article  PubMed  CAS  Google Scholar 

  • Kruse S, Japha T, Tedner M, Sparholt SH, Forster J, Kuehr J, Deichmann KA (1999) The polymorphisms S503P and Q576R in the interleukin-4 receptor alpha gene are associated with atopy and influence the signal transduction. Immunology 96:365–371

    Article  PubMed  CAS  Google Scholar 

  • Kwa D, van Rij RP, Boeser-Nunnink B, Vingerhoed J, Schuitemaker H (2003) Association between an interleukin-4 promoter polymorphism and the acquisition of CXCR4 using HIV-1 variants. AIDS 17:981–985

    Article  PubMed  CAS  Google Scholar 

  • Ledru E, Fevrier M, Lecoeur H, Garcia S, Boullier S, Gougeon ML (2003) A nonsecreted variant of interleukin-4 is associated with apoptosis: implication for the T helper-2 polarization in HIV infection. Blood 101:3102–3105

    Article  PubMed  CAS  Google Scholar 

  • Libert F, Cochaux P, Beckman G, Samson M, Aksenova M, Cao A, Czeizel A, Claustres M, de la Rua C, Ferrari M, Ferrec C, Glover G, Grinde B, Guran S, Kucinskas V, Lavinha J, Mercier B, Ogur G, Peltonen L, Rosatelli C, Schwartz M, Spitsyn V, Timar L, Beckman L, Parmentier M, Vassart G (1998) The deltaccr5 mutation conferring protection against HIV-1 in Caucasian populations has a single and recent origin in Northeastern Europe. Hum Mol Genet 7:399–406

    Article  PubMed  CAS  Google Scholar 

  • Lorenzo JI, Moscardo F, Lopez-Aldeguer J, Aznar JA (2001) Progression to acquired immunodeficiency syndrome in 94 human immunodeficiency virus-positive hemophiliacs with long-term follow-up. Haematologica 86:291–296

    PubMed  CAS  Google Scholar 

  • Lozano F, Places L, Vila JM, Padilla O, Arman M, Gimferrer I, Suarez B, Lopez de la Iglesia A, Miserachs N, Vives J (2001) Identification of a novel single-nucleotide polymorphism (Val554Ile) and definition of eight common alleles for human IL4RA exon 11. Tissue Antigens 57:216–220

    Article  PubMed  CAS  Google Scholar 

  • Maggi E, Mazzetti M, Ravina A, Annunziato F, de Carli M, Piccinni MP, Manetti R, Carbonari M, Pesce AM, del Prete G (1994) Ability of HIV to promote a TH1 to TH0 shift and to replicate preferentially in TH2 and TH0 cells. Science 265:244–248

    Article  PubMed  CAS  Google Scholar 

  • Magierowska M, Theodorou I, Debre P, Sanson F, Autran B, Riviere Y, Charron D, Costagliola D (1999) Combined genotypes of CCR5, CCR2, SDF1, and HLA genes can predict the long-term nonprogressor status in human immunodeficiency virus-1-infected individuals. Blood 93:936–941

    PubMed  CAS  Google Scholar 

  • Martin MP, Gao X, Lee JH, Nelson GW, Detels R, Goedert JJ, Buchbinder S, Hoots K, Vlahov D, Trowsdale J, Wilson M, O'Brien SJ, Carrington M (2002) Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS. Nat Genet 31:429–434

    PubMed  CAS  Google Scholar 

  • Martin MP, Lederman MM, Hutcheson HB, Goedert JJ, Nelson GW, van Kooyk Y, Detels R, Buchbinder S, Hoots K, Vlahov D, O'Brien SJ, Carrington M (2004) Association of DC-SIGN promoter polymorphism with increased risk for parenteral, but not mucosal, acquisition of human immunodeficiency virus type 1 infection. J Virol 78:14053–14056

    Article  PubMed  CAS  Google Scholar 

  • Meyaard L, Hovenkamp E, Keet IP, Hooibrink B, de Jong IH, Otto SA, Miedema F (1996) Single cell analysis of IL-4 and IFN-gamma production by T cells from HIV-infected individuals: decreased IFN-gamma in the presence of preserved IL-4 production. J Immunol 157:2712–2718

    PubMed  CAS  Google Scholar 

  • Mirel DB, Valdes AM, Lazzeroni LC, Reynolds RL, Erlich HA, Noble JA (2002) Association of IL4R haplotypes with type 1 diabetes. Diabetes 51:3336–3341

    Article  PubMed  CAS  Google Scholar 

  • Mitsuyasu H, Izuhara K, Mao XQ, Gao PS, Arinobu Y, Enomoto T, Kawai M, Sasaki S, Dake Y, Hamasaki N, Shirakawa T, Hopkin JM (1998) Ile50Val variant of IL4R alpha upregulates IgE synthesis and associates with atopic asthma. Nat Genet 19:119–120

    Article  PubMed  CAS  Google Scholar 

  • Mitsuyasu H, Yanagihara Y, Mao XQ, Gao PS, Arinobu Y, Ihara K, Takabayashi A, Hara T, Enomoto T, Sasaki S, Kawai M, Hamasaki N, Shirakawa T, Hopkin JM, Izuhara K (1999) Cutting edge: dominant effect of Ile50Val variant of the human IL-4 receptor alpha-chain in IgE synthesis. J Immunol 162:1227–1231

    PubMed  CAS  Google Scholar 

  • Modi WS, O'Brien TR, Vlahov D, Buchbinder S, Gomperts E, Phair J, O'Brien SJ, Winkler C (2003) Haplotype diversity in the interleukin-4 gene is not associated with HIV-1 transmission and AIDS progression. Immunogenetics 55:157–164

    Article  PubMed  CAS  Google Scholar 

  • Montoro JB, Oliveras J, Lorenzo JI, Tusell JM, Altisent C, Molina R, Ayestaran AI (1995) An association between clotting factor concentrates use and mortality in human immunodeficiency virus-infected hemophilic patients. Blood 86:2213–2219

    PubMed  CAS  Google Scholar 

  • Morawetz RA, Rizzardi GP, Glauser D, Rutschmann O, Hirschel B, Perrin L, Opravil M, Flepp M, von Overbeck J, Glauser MP, Ghezzi S, Vicenzi E, Poli G, Lazzarin A, Pantaleo G (1997) Genetic polymorphism of CCR5 gene and HIV disease: the heterozygous (CCR5/delta ccr5) genotype is neither essential nor sufficient for protection against disease progression. Swiss HIV Cohort. Eur J Immunol 27:3223–3227

    Article  PubMed  CAS  Google Scholar 

  • Mueller TD, Zhang JL, Sebald W, Duschl A (2002) Structure, binding, and antagonists in the IL-4/IL-13 receptor system. Biochim Biophys Acta 1592:237–250

    Article  PubMed  CAS  Google Scholar 

  • Nakayama EE, Hoshino Y, Xin X, Liu H, Goto M, Watanabe N, Taguchi H, Hitani A, Kawana-Tachikawa A, Fukushima M, Yamada K, Sugiura W, Oka SI, Ajisawa A, Sato H, Takebe Y, Nakamura T, Nagai Y, Iwamoto A, Shioda T (2000) Polymorphism in the interleukin-4 promoter affects acquisition of human immunodeficiency virus type 1 syncytium-inducing phenotype. J Virol 74:5452–5459

    Article  PubMed  CAS  Google Scholar 

  • Nakayama EE, Meyer L, Iwamoto A, Persoz A, Nagai Y, Rouzioux C, Delfraissy JF, Debre P, McIlroy D, Theodorou I, Shioda T (2002) Protective effect of interleukin-4 −589T polymorphism on human immunodeficiency virus type 1 disease progression: relationship with virus load. J Infect Dis 185:1183–1186

    Article  PubMed  CAS  Google Scholar 

  • Nelms K, Keegan AD, Zamorano J, Ryan JJ, Paul WE (1999) The IL-4 receptor: signaling mechanisms and biologic functions. Annu Rev Immunol 17:701–738

    Article  PubMed  CAS  Google Scholar 

  • Nolan D, Gaudieri S, John M, Mallal S (2004) Impact of host genetics on HIV disease progression and treatment: new conflicts on an ancient battleground. AIDS 18:1231–1240

    Article  PubMed  CAS  Google Scholar 

  • O'Brien SJ, Nelson GW (2004) Human genes that limit AIDS. Nat Genet 36:565–574

    Article  PubMed  CAS  Google Scholar 

  • Ober C, Leavitt SA, Tsalenko A, Howard TD, Hoki DM, Daniel R, Newman DL, Wu X, Parry R, Lester LA, Solway J, Blumenthal M, King RA, Xu J, Meyers DA, Bleecker ER, Cox NJ (2000) Variation in the interleukin 4-receptor alpha gene confers susceptibility to asthma and atopy in ethnically diverse populations. Am J Hum Genet 66:517–526

    Article  PubMed  CAS  Google Scholar 

  • Patterson BK, Czerniewski M, Andersson J, Sullivan Y, Su F, Jiyamapa D, Burki Z, Landay A (1999) Regulation of CCR5 and CXCR4 expression by type 1 and type 2 cytokines: CCR5 expression is downregulated by IL-10 in CD4-positive lymphocytes. Clin Immunol 91:254–262

    Article  PubMed  CAS  Google Scholar 

  • Pedraza MA, del Romero J, Roldan F, Garcia S, Ayerbe MC, Noriega AR, Alcami J (1999) Heterosexual transmission of HIV-1 is associated with high plasma viral load levels and a positive viral isolation in the infected partner. J Acquir Immune Defic Syndr 21:120–125

    PubMed  CAS  Google Scholar 

  • Penn ML, Grivel JC, Schramm B, Goldsmith MA, Margolis L (1999) CXCR4 utilization is sufficient to trigger CD4+ T cell depletion in HIV-1-infected human lymphoid tissue. Proc Natl Acad Sci U S A 19(96):663–668

    Article  Google Scholar 

  • Plana M, Garcia F, Gallart T, Tortajada C, Soriano A, Palou E, Maleno MJ, Barcelo JJ, Vidal C, Cruceta A, Miro JM, Gatell JM (2000) Immunological benefits of antiretroviral therapy in very early stages of asymptomatic chronic HIV-1 infection. AIDS 14:1921–1933

    Article  PubMed  CAS  Google Scholar 

  • Risma KA, Wang N, Andrews RP, Cunningham CM, Ericksen MB, Bernstein JA, Chakraborty R, Hershey GK (2002) V75R576 IL-4 receptor alpha is associated with allergic asthma and enhanced IL-4 receptor function. J Immunol 169:1604–1610

    PubMed  CAS  Google Scholar 

  • Robinson DS, O'Garra A (2002) Further checkpoints in Th1 development. Immunity 16:755–758

    Article  PubMed  CAS  Google Scholar 

  • Rosa-Rosa L, Zimmermann N, Bernstein JA, Rothenberg ME, Khurana Hershey GK (1999) The R576 IL-4 receptor alpha allele correlates with asthma severity. J Allergy Clin Immunol 104:1008–1014

    Article  PubMed  CAS  Google Scholar 

  • Rosenwasser LJ, Klemm DJ, Dresback JK, Inamura H, Mascali JJ, Klinnert M, Borish L (1995) Promoter polymorphisms in the chromosome 5 gene cluster in asthma and atopy. Clin Exp Allergy 25(Suppl 2):74–78

    Article  PubMed  Google Scholar 

  • Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM, Saragosti S, Lapoumeroulie C, Cognaux J, Forceille C, Muyldermans G, Verhofstede C, Burtonboy G, Georges M, Imai T, Rana S, Yi Y, Smyth RJ, Collman RG, Doms RW, Vassart G, Parmentier M (1996) Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 382:722–725

    Article  PubMed  CAS  Google Scholar 

  • Schinkel J, Langendam MW, Coutinho RA, Krol A, Brouwer M, Schuitemaker H (1999) No evidence for an effect of the CCR5 delta32/+ and CCR2b 64I/+ mutations on human immunodeficiency virus (HIV)-1 disease progression among HIV-1-infected injecting drug users. J Infect Dis 179:825–831

    Article  PubMed  CAS  Google Scholar 

  • Shin HD, Winkler C, Stephens JC, Bream J, Young H, Goedert JJ, O'Brien TR, Vlahov D, Buchbinder S, Giorgi J, Rinaldo C, Donfield S, Willoughby A, O'Brien SJ, Smith MW (2000) Genetic restriction of HIV-1 pathogenesis to AIDS by promoter alleles of IL10. Proc Natl Acad Sci U S A 97:14467–14472

    Article  PubMed  CAS  Google Scholar 

  • Singh KK, Hughes MD, Chen J, Spector SA (2004) Lack of protective effects of interleukin-4 −589-C/T polymorphism against HIV-1-related disease progression and central nervous system impairment, in children. J Infect Dis 189:587–592

    Article  PubMed  CAS  Google Scholar 

  • Soriano A, Martinez C, Garcia F, Plana M, Palou E, Lejeune M, Arostegui JI, De Lazzari E, Rodriguez C, Barrasa A, Lorenzo JI, Alcami J, del Romero J, Miro JM, Gatell JM, Gallart T (2002) Plasma stromal cell-derived factor (SDF)-1 levels, SDF1-3′A genotype, and expression of CXCR4 on T lymphocytes: their impact on resistance to human immunodeficiency virus type 1 infection and its progression. J Infect Dis 186:922–931

    Article  PubMed  CAS  Google Scholar 

  • Stephens HA (2005) HIV-1 diversity versus HLA class I polymorphism. Trends Immunol 26:41–47

    Article  PubMed  CAS  Google Scholar 

  • Suzuki Y, Koyanagi Y, Tanaka Y, Murakami T, Misawa N, Maeda N, Kimura T, Shida H, Hoxie JA, O'Brien WA, Yamamoto N (1999) Determinant in human immunodeficiency virus type 1 for efficient replication under cytokine-induced CD4(+) T-helper 1 (Th1)- and Th2-type conditions. J Virol 73:316–324

    PubMed  CAS  Google Scholar 

  • Tang J, Kaslow RA (2003) The impact of host genetics on HIV infection and disease progression in the era of highly active antiretroviral therapy. AIDS 17(Suppl 4):S51–S60

    Article  PubMed  Google Scholar 

  • Theodorou I, Capoulade C, Combadiere C, Debre P (2003) Genetic control of HIV disease. Trends Microbiol 11:392–397

    Article  PubMed  CAS  Google Scholar 

  • Torres Y, Medrano FJ, Rey C, Calderon EJ, Sanchez-Quijano A, Lissen E, Leal M (1998) Evidence for a role of T-helper type 2 cytokines in the acquisition of human immunodeficiency virus syncytium-inducing phenotype. Eur J Clin Invest 28:930–936

    Article  PubMed  CAS  Google Scholar 

  • Trikalinos TA, Ntzani EE, Contopoulos-Ioannidis DG, Ioannidis JP (2004) Establishment of genetic associations for complex diseases is independent of early study findings. Eur J Hum Genet 12:762–769

    Article  PubMed  CAS  Google Scholar 

  • Valentin A, Lu W, Rosati M, Schneider R, Albert J, Karlsson A, Pavlakis GN (1998) Dual effect of interleukin 4 on HIV-1 expression: implications for viral phenotypic switch and disease progression. Proc Natl Acad Sci U S A 95:8886–8891

    Article  PubMed  CAS  Google Scholar 

  • Vasilescu A, Heath SC, Ivanova R, Hendel H, Do H, Mazoyer A, Khadivpour E, Goutalier FX, Khalili K, Rappaport J, Lathrop GM, Matsuda F, Zagury JF (2003) Genomic analysis of Th1–Th2 cytokine genes in an AIDS cohort: identification of IL4 and IL10 haplotypes associated with the disease progression. Genes Immun 4:441–449

    Article  PubMed  CAS  Google Scholar 

  • Vasilescu A, Heath SC, Diop G, Do H, Hirtzig T, Hendel H, Bertin-Maghit S, Rappaport J, Therwath A, Lathrop GM, Matsuda F, Zagury JF (2004) Genomic analysis of Fas and FasL genes and absence of correlation with disease progression in AIDS. Immunogenetics 56:56–60

    Article  PubMed  CAS  Google Scholar 

  • Wang J, Roderiquez G, Oravecz T, Norcross MA (1998) Cytokine regulation of human immunodeficiency virus type 1 entry and replication in human monocytes/macrophages through modulation of CCR5 expression. J Virol 72:7642–7647

    PubMed  CAS  Google Scholar 

  • Winkler C, Modi W, Smith MW, Nelson GW, Wu X, Carrington M, Dean M, Honjo T, Tashiro K, Yabe D, Buchbinder S, Vittinghoff E, Goedert JJ, O'Brien TR, Jacobson LP, Detels R, Donfield S, Willoughby A, Gomperts E, Vlahov D, Phair J, O'Brien SJ (1998) Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC). Science 279:389–393

    Article  PubMed  CAS  Google Scholar 

  • Xu J, Turner A, Little J, Bleecker ER, Meyers DA (2002) Positive results in association studies are associated with departure from Hardy–Weinberg equilibrium: hint for genotyping error? Hum Genet 111:573–574

    Article  PubMed  Google Scholar 

  • Zoeteweij JP, Golding H, Mostowski H, Blauvelt A (1998) Cytokines regulate expression and function of the HIV coreceptor CXCR4 on human mature dendritic cells. J Immunol 161:3219–3223

    PubMed  CAS  Google Scholar 

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Acknowledgements

This study was supported by research grants FIS99/0289 and FIS03/1200 (FIS corresponds to “Fondo de Investigación Sanitaria” of the Spanish Ministry of Health; T. Gallart). Research grant FIPSE36259-01 (FIPSE stands for “Fundación para la investigación y prevención sobre el SIDA”; T. Gallart), the “Red Temática de Investigación sobre el SIDA” (FIS2003-2005; J.M. Gatell), the Catalonian Television Marathon, Marató TV3 2000-3110 and 2003-020510 (F. Lozano), and the “Prof. Máximo Soriano Foundation” also provided financial support. A. Soriano received a research award from “Hospital Clínic de Barcelona” after his residency in internal medicine (infectious diseases and AIDS) for study on host factors and susceptibility resistance to HIV infection. FIPSE is a nonprofit foundation for the research and prevention of AIDS, integrated by the Spanish Ministry of Health, Abbott Laboratories, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Merck, Sharp and Dohme, and Roche.

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Authors and Affiliations

  1. Service of Infectious Diseases and AIDS Unit, Hospital Clínic de Barcelona, Villarroel, 170, 08036, Barcelona, Spain

    Alex Soriano, Felipe García, Meritxell Nomdedéu, José M. Miró & José M. Gatell

  2. Service of Immunology, Hospital Clínic de Barcelona, Barcelona, Spain

    Francisco Lozano, Harold Oliva, Montserrat Plana, Jordi Vives & Teresa Gallart

  3. AIDS Research Group of IDIBAPS (“Institut d'Investigacions Biomèdiques August Pi I Sunyer”), Faculty of Medicine, University of Barcelona, Barcelona, Spain

    Harold Oliva, Felipe García, Meritxell Nomdedéu, Elisa De Lazzari, Montserrat Plana, José M. Miró, José M. Gatell & Teresa Gallart

  4. Unit of Biostatistics, Hospital Clínic de Barcelona, Barcelona, Spain

    Elisa De Lazzari

  5. Centro Médico Sandoval, Madrid, Spain

    Carmen Rodríguez, Alicia Barrasa & Jorge del Romero

  6. Department of Hematology, Hospital La Fe, Valencia, Spain

    José I. Lorenzo

Authors
  1. Alex Soriano
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  2. Francisco Lozano
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  3. Harold Oliva
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  4. Felipe García
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  5. Meritxell Nomdedéu
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  6. Elisa De Lazzari
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  7. Carmen Rodríguez
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  8. Alicia Barrasa
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  9. José I. Lorenzo
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  10. Jorge del Romero
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  11. Montserrat Plana
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  12. José M. Miró
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  13. José M. Gatell
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  14. Jordi Vives
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  15. Teresa Gallart
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Corresponding authors

Correspondence to Alex Soriano or Teresa Gallart.

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Soriano, A., Lozano, F., Oliva, H. et al. Polymorphisms in the interleukin-4 receptor α chain gene influence susceptibility to HIV-1 infection and its progression to AIDS. Immunogenetics 57, 644–654 (2005). https://doi.org/10.1007/s00251-005-0041-x

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  • DOI: https://doi.org/10.1007/s00251-005-0041-x

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