1887

Abstract

CXCR4 functions as an infection receptor of X4 human immunodeficiency virus type 1 (HIV-1) . CXCR4 is glycosylated at the N-terminal extracellular region, which is important for viral envelope (Env) protein binding. We compared the effects of CXCR4 glycan on the CD4-dependent and –independent infections in human cells by X4 viruses. We found that transduction mediated by Env proteins of CD4-independent HIV-1 strains increased up to 5.5-fold in cells expressing unglycosylated CXCR4, suggesting that the CXCR4 glycan inhibits CD4-independent X4 virus infection. Co-expression of CD4 on the target cell surface or pre-incubation of virus particles with soluble CD4 abrogates the glycan-mediated inhibition of X4 virus infection, suggesting that interaction of Env protein with CD4 counteracts the inhibition. These findings indicate that it will be advantageous for X4 HIV-1 to remain CD4-dependent. A structural model that explains the glycan-mediated inhibition is discussed.

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2007-11-01
2024-04-19
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References

  1. Berger E. A., Doms R. W., Fenyo E. M., Korber B. T., Littman D. R., Moore J. P., Sattentau Q. J., Schuitemaker H., Sodroski J., Weiss R. A. 1998; A new classification for HIV-1. Nature 391:240 [CrossRef]
    [Google Scholar]
  2. Bhattacharya J., Peters P. J., Clapham P. R. 2003; CD4-independent infection of HIV and SIV: implications for envelope conformation and cell tropism in vivo. AIDS 17 (Suppl. 4):S35–S43 [CrossRef]
    [Google Scholar]
  3. Brelot A., Heveker N., Pleskoff O., Sol N., Alizon M. 1997; Role of the first and third extracellular domains of CXCR-4 in human immunodeficiency virus coreceptor activity. J Virol 71:4744–4751
    [Google Scholar]
  4. Brelot A., Heveker N., Montes M., Alizon M. 2000; Identification of residues of CXCR4 critical for human immunodeficiency virus coreceptor and chemokine receptor activities. J Biol Chem 275:23736–23744 [CrossRef]
    [Google Scholar]
  5. Chabot D. J., Broder C. C. 2000; Substitutions in a homologous region of extracellular loop 2 of CXCR4 and CCR5 alter coreceptor activities for HIV-1 membrane fusion and virus entry. J Biol Chem 275:23774–23782 [CrossRef]
    [Google Scholar]
  6. Chabot D. J., Zhang P. F., Quinnan G. V., Broder C. C. 1999; Mutagenesis of CXCR4 identifies important domains for human immunodeficiency virus type 1 X4 isolate envelope-mediated membrane fusion and virus entry and reveals cryptic coreceptor activity for R5 isolates. J Virol 73:6598–6609
    [Google Scholar]
  7. Chabot D. J., Chen H., Dimitrov D. S., Broder C. C. 2000; N-linked glycosylation of CXCR4 masks coreceptor function for CCR5-dependent human immunodeficiency virus type 1 isolates. J Virol 74:4404–4413 [CrossRef]
    [Google Scholar]
  8. Chang L. J., Urlacher V., Iwakuma T., Cui Y., Zucali J. 1999; Efficacy and safety analyses of a recombinant human immunodeficiency virus type 1 derived vector system. Gene Ther 6:715–728 [CrossRef]
    [Google Scholar]
  9. Dimitrov D. S. 1997; How do viruses enter cells? The HIV coreceptors teach us a lesson of complexity. Cell 91:721–730 [CrossRef]
    [Google Scholar]
  10. Doranz B. J., Orsini M. J., Turner J. D., Hoffman T. L., Berson J. F., Hoxie J. A., Peiper S. C., Brass L. F., Doms R. W. 1999; Identification of CXCR4 domains that support coreceptor and chemokine receptor functions. J Virol 73:2752–2761
    [Google Scholar]
  11. Dumonceaux J., Nisole S., Chanel C., Quivet L., Amara A., Baleux F., Briand P., Hazan U. 1998; Spontaneous mutations in the env gene of the human immunodeficiency virus type 1 NDK isolate are associated with a CD4-independent entry phenotype. J Virol 72:512–519
    [Google Scholar]
  12. Edinger A. L., Blanpain C., Kunstman K. J., Wolinsky S. M., Parmentier M., Doms R. W. 1999; Functional dissection of CCR5 coreceptor function through the use of CD4-independent simian immunodeficiency virus strains. J Virol 73:4062–4073
    [Google Scholar]
  13. Edwards T. G., Hoffman T. L., Baribaud F., Wyss S., LaBranche C. C., Romano J., Adkinson J., Sharron M., Hoxie J. A., Doms R. W. 2001; Relationships between CD4 independence, neutralization sensitivity, and exposure of a CD4-induced epitope in a human immunodeficiency virus type 1 envelope protein. J Virol 75:5230–5239 [CrossRef]
    [Google Scholar]
  14. Hart T. K., Kirsh R., Ellens H., Sweet R. W., Lambert D. M., Petteway S. R., Leary J., Bugelski P. J. 1991; Binding of soluble CD4 proteins to human immunodeficiency virus type 1 and infected cells induces release of envelope glycoprotein gp120. Proc Natl Acad Sci U S A 88:2189–2193 [CrossRef]
    [Google Scholar]
  15. Hoffman T. L., LaBranche C. C., Zhang W., Canziani G., Robinson J., Chaiken I., Hoxie J. A., Doms R. W. 1999; Stable exposure of the coreceptor-binding site in a CD4-independent HIV-1 envelope protein. Proc Natl Acad Sci U S A 96:6359–6364 [CrossRef]
    [Google Scholar]
  16. Hoffman T. L., Canziani G., Jia L., Rucker J., Doms R. W. 2000; A biosensor assay for studying ligand-membrane receptor interactions: binding of antibodies and HIV-1 Env to chemokine receptors. Proc Natl Acad Sci U S A 97:11215–11220 [CrossRef]
    [Google Scholar]
  17. Huang X., Shen J., Cui M., Shen L., Luo X., Ling K., Pei G., Jiang H., Chen K. 2003; Molecular dynamics simulations on SDF-1alpha: binding with CXCR4 receptor. Biophys J 84:171–184 [CrossRef]
    [Google Scholar]
  18. Huang C. C., Tang M., Zhang M. Y., Majeed S., Montabana E., Stanfield R. L., Dimitrov D. S., Korber B., Sodroski J. other authors 2005; Structure of a V3-containing HIV-1 gp120 core. Science 310:1025–1028 [CrossRef]
    [Google Scholar]
  19. Iwakuma T., Cui Y., Chang L. J. 1999; Self-inactivating lentiviral vectors with U3 and U5 modifications. Virology 261:120–132 [CrossRef]
    [Google Scholar]
  20. Kajumo F., Thompson D. A., Guo Y., Dragic T. 2000; Entry of R5X4 and X4 human immunodeficiency virus type 1 strains is mediated by negatively charged and tyrosine residues in the amino-terminal domain and the second extracellular loop of CXCR4. Virology 271:240–247 [CrossRef]
    [Google Scholar]
  21. Kinomoto M., Yokoyama M., Sato H., Kojima A., Kurata T., Ikuta K., Sata T., Tokunaga K. 2005; Amino acid 36 in the human immunodeficiency virus type 1 gp41 ectodomain controls fusogenic activity: implications for the molecular mechanism of viral escape from a fusion inhibitor. J Virol 79:5996–6004 [CrossRef]
    [Google Scholar]
  22. Kolchinsky P., Kiprilov E., Sodroski J. 2001; Increased neutralization sensitivity of CD4-independent human immunodeficiency virus variants. J Virol 75:2041–2050 [CrossRef]
    [Google Scholar]
  23. Kubo Y., Ono T., Ogura M., Ishimoto A., Amanuma H. 2002; A glycosylation-defective variant of the ecotropic murine retrovirus receptor is expressed in rat XC cells. Virology 303:338–344 [CrossRef]
    [Google Scholar]
  24. Kubo Y., Ishimoto A., Amanuma H. 2003; N-Linked glycosylation is required for XC cell-specific syncytium formation by the R peptide-containing envelope protein of ecotropic murine leukemia viruses. J Virol 77:7510–7516 [CrossRef]
    [Google Scholar]
  25. Kubo Y., Ishimoto A., Ono T., Yoshii H., Tominaga C., Mitani C., Amanuma H., Yamamoto N. 2004; Determinant for the inhibition of ecotropic murine leukemia virus infection by N-linked glycosylation of the rat receptor. Virology 330:82–91 [CrossRef]
    [Google Scholar]
  26. Marin M., Lavillette D., Kelly S. M., Kabat D. 2003; N-linked glycosylation and sequence changes in a critical negative control region of the ASCT1 and ASCT2 neutral amino acid transporters determine their retroviral receptor functions. J Virol 77:2936–2945 [CrossRef]
    [Google Scholar]
  27. Martin K. A., Wyatt R., Farzan M., Choe H., Marcon L., Desjardins E., Robinson J., Sodroski J., Gerard C., Gerard N. P. 1997; CD4-independent binding of SIV gp120 to rhesus CCR5. Science 278:1470–1473 [CrossRef]
    [Google Scholar]
  28. Moore J. P., McKeating J. A., Weiss R. A., Sattentau Q. J. 1990; Dissociation of gp120 from HIV-1 virions induced by soluble CD4. Science 250:1139–1142 [CrossRef]
    [Google Scholar]
  29. Naldini L., Blomer U., Gallay P., Ory D., Mulligan R., Gage F. H., Verma I. M., Trono D. 1996; In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272:263–267 [CrossRef]
    [Google Scholar]
  30. Overbaugh J., Miller A. D., Eiden M. V. 2001; Receptors and entry cofactors for retroviruses include single and multiple transmembrane-spanning proteins as well as newly described glycophosphatidylinositol-anchored and secreted proteins. Microbiol Mol Biol Rev 65:371–389 (table of contents [CrossRef]
    [Google Scholar]
  31. Palczewski K., Kumasaka T., Hori T., Behnke C. A., Motoshima H., Fox B. A., Le Trong I., Teller D. C., Okada T. other authors 2000; Crystal structure of rhodopsin: A G protein-coupled receptor. Science 289:739–745 [CrossRef]
    [Google Scholar]
  32. Picard L., Wilkinson D. A., McKnight A., Gray P. W., Hoxie J. A., Clapham P. R., Weiss R. A. 1997; Role of the amino-terminal extracellular domain of CXCR-4 in human immunodeficiency virus type 1 entry. Virology 231:105–111 [CrossRef]
    [Google Scholar]
  33. Ponder J. W., Case D. A. 2003; Force fields for protein simulations. Adv Protein Chem 66:27–85
    [Google Scholar]
  34. Potempa S., Picard L., Reeves J. D., Wilkinson D., Weiss R. A., Talbot S. J. 1997; CD4-independent infection by human immunodeficiency virus type 2 strain ROD/B: the role of the N-terminal domain of CXCR-4 in fusion and entry. J Virol 71:4419–4424
    [Google Scholar]
  35. Puffer B. A., Pohlmann S., Edinger A. L., Carlin D., Sanchez M. D., Reitter J., Watry D. D., Fox H. S., Desrosiers R. C., Doms R. W. 2002; CD4 independence of simian immunodeficiency virus Envs is associated with macrophage tropism, neutralization sensitivity, and attenuated pathogenicity. J Virol 76:2595–2605 [CrossRef]
    [Google Scholar]
  36. Schenten D., Marcon L., Karlsson G. B., Parolin C., Kodama T., Gerard N., Sodroski J. 1999; Effects of soluble CD4 on simian immunodeficiency virus infection on CD4-positive and CD4-negative cells. J Virol 73:5373–5380
    [Google Scholar]
  37. Soda Y., Shimizu N., Jinno A., Liu H. Y., Kanbe K., Kitamura T., Hoshino H. 1999; Establishment of a new system for determination of coreceptor usages of HIV based on the human glioma NP-2 cell line. Biochem Biophys Res Commun 258:313–321 [CrossRef]
    [Google Scholar]
  38. Sommerfelt M. A. 1999; Retrovirus receptors. J Gen Virol 80:3049–3064
    [Google Scholar]
  39. Tailor C. S., Nouri A., Kabat D. 2000; Cellular and species resistance to murine amphotropic, gibbon ape, and feline subgroup C leukemia viruses is strongly influenced by receptor expression levels and by receptor masking mechanisms. J Virol 74:9797–9801 [CrossRef]
    [Google Scholar]
  40. Tanaka R., Yoshida A., Murakami T., Baba E., Lichtenfeld J., Omori T., Kimura T., Tsurutani N., Fujii N. Jr other authors 2001; Unique monoclonal antibody recognizing the third extracellular loop of CXCR4 induces lymphocyte agglutination and enhances human immunodeficiency virus type 1-mediated syncytium formation and productive infection. J Virol 75:11534–11543 [CrossRef]
    [Google Scholar]
  41. Thomas E. R., Shotton C., Weiss R. A., Clapham P. R., McKnight A. 2003; CD4-dependent and CD4-independent HIV-2: consequences for neutralization. AIDS 17:291–300 [CrossRef]
    [Google Scholar]
  42. Thordsen I., Polzer S., Schreiber M. 2002; Infection of cells expressing CXCR4 mutants lacking N-glycosylation at the N-terminal extracellular domain is enhanced for R5X4-dualtropic human immunodeficiency virus type-1. BMC Infect Dis 2:31 [CrossRef]
    [Google Scholar]
  43. Wang J., Babcock G. J., Choe H., Farzan M., Sodroski J., Gabuzda D. 2004; N-linked glycosylation in the CXCR4 N-terminus inhibits binding to HIV-1 envelope glycoproteins. Virology 324:140–150 [CrossRef]
    [Google Scholar]
  44. Wilson C. A., Eiden M. V. 1991; Viral and cellular factors governing hamster cell infection by murine and gibbon ape leukemia viruses. J Virol 65:5975–5982
    [Google Scholar]
  45. Zhou N., Luo Z., Luo J., Liu D., Hall J. W., Pomerantz R. J., Huang Z. 2001; Structural and functional characterization of human CXCR4 as a chemokine receptor and HIV-1 co-receptor by mutagenesis and molecular modeling studies. J Biol Chem 276:42826–42833 [CrossRef]
    [Google Scholar]
  46. Zhu P., Liu J., Bess J. Jr, Chertova E., Lifson J. D., Grise H., Ofek G. A., Taylor K. A., Roux K. H. 2006; Distribution and three-dimensional structure of AIDS virus envelope spikes. Nature 441:847–852 [CrossRef]
    [Google Scholar]
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