Skip to main content
SpringerLink
Log in

Sequence variants of chemokine receptor genes and susceptibility to HIV-1 infection

  • Original Article
  • Published:
Journal of Applied Genetics Aims and scope Submit manuscript

Abstract

Genetic susceptibility to HIV infection was previously proven to be influenced by some chemokine receptor polymorphisms clustering on chromosome 3p21. Here the influence of 5 genetic variants was studied: Δ32CCR5, G(-2459)ACCR5, G190ACCR2, G744ACX3CR1 and C838TCX3CR1. They were screened in a cohort of 168 HIV-1 positive adults [HIV(+) group] and 151 newborns [control group] from northwestern Poland. PCR-RFLP was performed to screen for the variants (except for A32CCR5 polymorphism, where PCR fragment size was sufficient to identify the alleles) and then electrophoresed on agarose gel to determine fragment size. Distribution of genotypes and alleles was not significantly different between the groups except for theCCR5 polymorphisms, with the A32 allele and the (-2459)ACCR5 allele more frequent among neonates than in the HIV(+) group. No Δ32/Δ32 homozygotes were found in the HIV(+) group, but 16.1% were Δ32/wt heterozygotes. In the control group, 1.3% were Δ32/Δ32 homozygotes and 26.0% were Δ32/wt heterozygotes. Linkage between the chemokine polymorphisms was calculated using the most informative loci for haplotype reconstruction. Haplotypes containing Δ32 CCR5,190GCCR2 and 744ACX3CR1 were found to be significantly more common in the control group. This suggests an association between these haplotypes and resistance to HIV-1 infection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Alkhatib G, Combardiere C, Broder CC, Feng Y, Kennedy PE, Murphy PM, Beger EA, 1996. CC-CKR: a RANTES, MIP1á, MIP1â receptor as a fusion cofactor for macrophage tropic HIV-1. Science 272: 1955–1958.

    Article  CAS  PubMed  Google Scholar 

  • Clark VJ, Dean M, 2004. Haplotype structure and linkage disequilibrium in chemokine and chemokine receptor genes. Hum Genomics 1: 255–273.

    CAS  PubMed  Google Scholar 

  • Combardiere C, Salzwedel K, Smith ED, Tiffany HL, Berger EA, Murphy PM, 1998. Identification of CX3CR1. J Biol Chem 273: 23799–23804.

    Article  Google Scholar 

  • Dragic T, Litwin V, Allaway GP, Martin SR, Huang Y, Nagashimak A, et al. 1996. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature 382: 667–673.

    Article  Google Scholar 

  • Duncan SR, Scott S, Duncan CJ, 2004. Reappraisal of the historical selective pressures for the CCR5-Δ32 mutation. J Med Genet 42: 205–208.

    Article  Google Scholar 

  • Faure S, Meyer L, Costagliola D, Vaneensberghe C, Genin E, Autran B, Delfraissy J, McDermot DH, Murphy PM, Debre P, Theodorou I, Combadiere C, 2000. Rapid progression to AIDS in HIV[sup +] individuals with a structural variant of the chemokine receptor CX[sub 3]CR1. Science 287: 2274–2278.

    Article  CAS  PubMed  Google Scholar 

  • Galvani AP, Slatkin M, 2003. Evaluating plague and smallpox as historical selective pressures for the CCR5-D32 HIV-resistance allele. Proc Natl Acad Sci USA 100: 15276–15279.

    Article  CAS  PubMed  Google Scholar 

  • Garin A, Pellet P, Deterre P, Debre P, Combardiere C, 2002. Cloning and functional characterization of the human fractalkine receptor promoter regions. Biochem J 368: 753–760.

    Article  CAS  PubMed  Google Scholar 

  • Garin A, Tarantino N, Faure S, Daoudi M, Lécureuil C, Bourdais A, et al. 2003. Two novel fully functional isoforms of CX3CR1 are potent HIV coreceptors. J Immunol 171: 5305–5312.

    CAS  PubMed  Google Scholar 

  • Garred P, Eugen-Olsen J, Iversen AK, Benfield TL, Svejgaard A, Hofmann B, 1997. 32 bp CCR-5 gene deletion and resistance to fast progression in HIV-1 infected heterozygotes. Lancet 349: 922–923.

    Article  Google Scholar 

  • Gonzales E, Bamshad M, Sato N, Dhanda R, Catano G, Cabrera S, 1999. Race-specific HIV-1 disease-modifying effects associated with CCR5 haplotypes. Proc Natl Acad Sci U S A 96: 12004–12009.

    Article  Google Scholar 

  • Hladik F, Liu H, Speelmon E, Livingston-Rosanoff D, Wilson S, et al. 2005. Combined effect of CCR5-A32 heterozygosity and the CCR5 promoter polymorphism-2459 A/G on CCR5 expression and resistance to human immunodeficiency virus type 1 transmission, 79: 11677–11684.

  • Jagodziński P, Lecybył R, Ignacak M, Juszczyk J, Trzeciak W, 2000. Distribution of Δ32 allele of the CCR5 gene in the population of Poland. J Hum Genet 45: 271–274

    Article  PubMed  Google Scholar 

  • Kristiansen TB, Knudsen TB, Ohlendorff S, Eugen-Olsen J, 2001. A new multiplex PCR strategy for the simultaneous determination of four genetic polymorphisms affecting HIV-1 disease progression. J Immunol Methods 252: 147–151.

    Article  CAS  PubMed  Google Scholar 

  • Laing KJ, Secombes CJ, 2004. Chemokines. Dev Comp Immunol 28: 443–460

    Article  CAS  PubMed  Google Scholar 

  • Lee B, Doranz BJ, Rana S, Yi Y, Mellado M, Frade JM, et al. 1998. Influence oftheCCR2-V64I polymorphism on human immunodeficiency virus type 1 coreceptor activity and on chemokine receptor function of CCR2b, CCR3, CCR5, and CXCR4. J Virol 72: 7450–7458.

    CAS  PubMed  Google Scholar 

  • Lewandowska M, Franciszkiewicz K, Prokop J, Ofori H, Jagodziński P, 2002. Distribution of two HIV-1-resistant polymorphisms (SDF1-3 A and CCR2-64I alleles) in the Polish population. J Hum. Genet 47: 585–589.

    Article  CAS  PubMed  Google Scholar 

  • Li C, Lu C, Hsieh P, Huang Y, Huang H, Ying TH, Shieh B, 2005. Distribution of human chemokine (C-C3-C) receptor 1 (CX3CR1) gene polymorphisms and haplotypes of the CC chemokine receptor 5 (CCR5) promoter in Chinese people and the effects of CCR5 haplotypes on CCR5 expression. Int J Immunogenet 32: 99–106.

    Article  CAS  PubMed  Google Scholar 

  • Lucotte G, Mercier G, 1998. Distribution of the CCR5 gene 32-bp deletion in Europe. J Acquir Immune Defic Syndr Hum Retrovirol 19: 174–177.

    CAS  PubMed  Google Scholar 

  • Magierowska M, Theodorou I, Debre P, Samson F, Autran B, Riviere Y, et al. 1999. Combined genotypes ofCCR5, CCR2, SDF1, andHLA genes can predict the long-term nonprogressor status in human immunodeficiency virus-1-infected individuals. Blood 93: 936–941.

    CAS  PubMed  Google Scholar 

  • Mangano A, Gonzalez E, Dhanda R, Catano G, Bamshad M, Bock A, et al. 2001. Concordance between the CC chemokine receptor 5 genetic determinants that alter risks of transmission and disease progression in children exposed perinatally to human immunodeficiency virus. J Infect Dis 183: 1574–1585.

    Article  CAS  PubMed  Google Scholar 

  • McDermott DH, Zimmerman PA, Guignard F, Kleeberger CA, Leitman SF, Murphy PM, 1998. CCR5 promoter polymorphism and HIV-1 disease progression. Multicenter AIDS Cohort Study (MACS). Lancet 352: 866–870.

    Article  CAS  PubMed  Google Scholar 

  • Moatti D, Faure S, Fumeron F, Amara Mel-W, Seknadji P, McDermott DH, et al. 2001. Polymorphism in the fractalkine receptor CX3CR1 as a genetic risk factor for coronary artery disease. Blood 97: 1925–1928.

    Article  CAS  PubMed  Google Scholar 

  • Mummidi S, Bamshad M, Ahuja SS, Gonzalez E, Feuillet PM, Begum K, et al. 2000. Evolution of human and non-human primate CC chemokine receptor 5 gene and mRNA. Potential roles for haplotype and mRNA diversity, differential haplotype-specific transcriptional activity, and altered transcription factor binding to polymorphic nucleotides in the pathogenesis of HIV-1 and simian immunodeficiency virus. J Biol Chem 275: 18946–18961.

    Article  CAS  PubMed  Google Scholar 

  • Nguyen L, Li M, Chaowanachan T, Hu DJ, Vanichseni S, Mock PA, et al. 2004. CCR5 promoter human haplogroups associated with HIV-1 disease progression in Thai injection drug users. AIDS 18: 1327–1333.

    Article  CAS  PubMed  Google Scholar 

  • Nishimura M, Umehara H, Nakayama T, Yoneda O, Hieshima K, Kakizaki M, et al. 2002. Dual functions of fractalkine/CX3CR1 in trafficking of circulating cytotoxic effector lymphocytes that are defined by CX3CR1 expression. J Immunol 168: 6173–6180.

    CAS  PubMed  Google Scholar 

  • O’Brien SJ, Moore JP, 2000. The effect of genetic variation in chemokines and their receptors on HIV transmission and progression to AIDS. Immunol rev 177: 99–111.

    Article  PubMed  Google Scholar 

  • O’Brien SJ, 1998. AIDS: a role for host genes. Hospital Practice 33: 53–56, 59–60, 66–73

    Article  PubMed  Google Scholar 

  • Rector A, Vermeire S, Thoelen I, Keyaerts E, Struyf F, Vlietinck R, et al. 2001. Analysis of the CC chemokine receptor 5 (CCR5) delta-32 polymorphism in inflammatory bowel disease. Hum Genet 108: 190–193.

    Article  CAS  PubMed  Google Scholar 

  • Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM, et al. 1996. Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 382: 722–725.

    Article  CAS  PubMed  Google Scholar 

  • Shrestha S, Strathdee SA, Galai N, Oleksyk T, Fallin MD, Mehta S, Schaid D, Vlahov D, O’Brien SJ, Smith MW, 2006. Behavioral risk exposure and host genetics of susceptibility to HIV-1 infection. J Infect Dis 193: 16–26.

    Article  CAS  PubMed  Google Scholar 

  • Stewart GJ, Ashton LJ, Biti RA, French RA, Bennetts BH, Newcombe NR, Benson EM, Carr A, Cooper DA, Kaldor JM, 1997. Increased frequency of CCR-5 delta 32 heterozygotes among long-term non-progressors with HIV-1 infection. The Australian Long-Term Non-Progressor Study Group. AIDS 11: 1833–1838.

    Article  CAS  PubMed  Google Scholar 

  • Tang J, Shelton B, Makhatadze NJ, Zhang Y, Schaen M, Louie LG, et al. 2002. Distribution of chemokine receptor CCR2 and CCR5 genotypes and their relative contribution to human immunodeficiency virus type 1 (HIV-1) seroconversion, early HIV-1 RNA concentration in plasma, and later disease progression. J Virol 76: 662–672.

    Article  CAS  PubMed  Google Scholar 

  • Umehara H, Bloom ET, Okazaki T, Nagano Y, Yoshie O, Imai T, 2004. Fractalkine in vascular biology: from basic research to clinical disease. Arterioscler Thromb Vasc Biol 24: 34–40.

    Article  CAS  PubMed  Google Scholar 

  • Vidal F, Vilades C, Domingo P, Broch M, Pedrol E, Dalmau D, et al. 2005. Spanish HIV-1-infected long-term nonprogressors of more than 15 years have an increased frequency of the CX3CR1 249I variant allele. 40:527–531.

Download references

Author information

Authors and Affiliations

  1. Department of Infectious Diseases and Hepatology, Pomeranian Medical University, Arkońska 4, 71–455, Szczecin, Poland

    M. Parczewski, M. Leszczyszyn-Pynka & A. Boroń-Kaczmarska

  2. Department of Laboratory Diagnostics & Molecular Medicine, Pomeranian Medical University, Szczecin, Poland

    M. Kaczmarczyk, G. Adler, A. Bińczak-Kuleta & A. Ciechanowicz

  3. Department of Neonatology, Pomeranian Medical University, Szczecin, Poland

    B. Łoniewska

Authors
  1. M. Parczewski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Leszczyszyn-Pynka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Kaczmarczyk
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Adler
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Bińczak-Kuleta
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. B. Łoniewska
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Boroń-Kaczmarska
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A. Ciechanowicz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Parczewski.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Parczewski, M., Leszczyszyn-Pynka, M., Kaczmarczyk, M. et al. Sequence variants of chemokine receptor genes and susceptibility to HIV-1 infection. J Appl Genet 50, 159–166 (2009). https://doi.org/10.1007/BF03195668

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03195668

Keywords

Search

Navigation