Virus Genes

, Volume 34, Issue 2, pp 93–109

The spreading of HIV-1 infection in the human organism is caused by fractalkine trafficking of the infected lymphocytes—a review, hypothesis and implications for treatment

Original Article

Abstract

The reviews on HIV-1/AIDS [1, 2, 3, 4, 5, 6, 7, 8] highlighted the mechanism by which HIV-1 virions utilize dendritic cells (DCs) for transport from the genitals, the portal of virus infection, to the draining lymph nodes where DCs carry HIV-1 virions and present viral antigens by HLA class I and II to CD4+ T cells. Interaction of the T cells with viral antigens presented by HLA class II molecules polarizes them to become Th2 cells, the targets of HIV-1 infection and producers of HIV-1 progeny virions. The T cells which interact with viral antigen presented by HLA class I polarize to become Th1 cells, which stimulate the CD8+ T cell precursors to develop into antiviral cytotoxic T cells. In addition, HIV-1 virions shed gp120 glycoprotein molecules which bind to IgE immunoglobulin molecules bound to FCεRI+ innate system cells (basophils, mast cells and monocytes) and induce them to release large amounts of Th2 cytokines (IL-4, IL-5, IL-10, IL-13), thereby creating an allergy-like condition. The present review attempts to define the role of chemokine receptors like CCR5 and CXCR4, and especially fractalkine receptor CX3CR1 in the trafficking of lymphocytes in healthy individuals and HIV-1/AIDS patients. The role of chemokine receptors as co-receptors for HIV-1 virion gp120 glycoprotein has been defined, but the role of fractalkine and fractalkine receptor has been clarified only recently [9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19]. In healthy individuals fractalkine is expressed by blood vessel endothelial cells and the CX3CR1 receptors are expressed on leukocytes that migrate in the peripheral blood in the direction of increased fractalkine concentration. In HIV-1/AIDS patients the virus-infected CD4+ Th2 cells migrate to organs that harbor the adaptive immune system cells in the thymus, genitals, gastrointestinal tract, and to the brain. A most significant finding which revealed the importance of the human CX3CR1 gene expression to the progression of the infection to the stage of AIDS was recently reported by Faure and collaborators [20, 21] who showed that the delayed or rapid progression to AIDS was affected in HIV-1-infected individuals who had inherited a fractalkine receptor gene with the polymorphisms V249I or T280M, respectively, located in the sixth and seventh transmembrane domains of CX3CR1 protein. The T280M mutation in the CX3CR1 gene caused a rapid progression to AIDS, while in patients with the V249I mutation progression to AIDS was much slower. These studies led to the idea that it might be possible to slow or prevent HIV-1/AIDS progression in HIV-1 patients by treating them with fractalkine antagonists that will bind to and inhibit the activity of the fractalkine receptor. It is hypothesized that treatment of HIV-1/AIDS patients with a combination of fractalkine antagonists, IL-4 antagonist IL-4δ2 and the adjuvant CpG ODN induced release of type I IFN from PDF, and may inhibit HIV-1 infection, especially in HAART-treated patients infected with drug-resistant HIV-1 mutants due to prevention of the availability of immune cells needed for the viral evasion of the immune response. The hypothesis implies that the advantage of the suggested mode of treatment of HIV-1-infected people is prevention of cellular processes that are used by the viral protein to cause immunodeficiency, and prevention of HIV-1 replication without induction of resistant mutants.

Keywords

HIV-1/AIDS Fractalkine Fractalkine receptor mutations HIV-1 damage to adaptive immune cells: thymus Lymph nodes Genitals Gastrointestinal tract Fractalkine antagonists IL-4 antagonist IL-4δ2 The adjuvant CpG ODN 

References

  1. 1.
    T.R. Mosman R.L. Coffman, Ann. Rev. Immunol. 7, 145–173, (1989)CrossRefGoogle Scholar
  2. 2.
    Y. Becker, Virus Genes 27, 269–282, (2003)PubMedCrossRefGoogle Scholar
  3. 3.
    Y. Becker, Virus Genes 28, 5–18, (2004)PubMedCrossRefGoogle Scholar
  4. 4.
    Y. Becker, Virus Genes 28, 319–331, (2004)PubMedCrossRefGoogle Scholar
  5. 5.
    Y. Becker, Virus Genes 29, 147–165, (2004)PubMedCrossRefGoogle Scholar
  6. 6.
    Y. Becker, ASM News 70, 565–570, (2004)Google Scholar
  7. 7.
    Y. Becker, Virus Genes 30, 251–266, (2005)PubMedCrossRefGoogle Scholar
  8. 8.
    Y. Becker, Virus Genes 31, 113–119, (2005)PubMedCrossRefGoogle Scholar
  9. 9.
    J.F. Bazan, K.B. Bacon, G. Hardiman, W. Wang, K. Soo, D. Rossi, D.R. Greaves, A. Zlotnik, T. Schall, J. Nature 385, 640–644, (1997)CrossRefGoogle Scholar
  10. 10.
    T. Imai, K. Hieshima, C. Haskell, M. Baba, M. Nagira, M. Nishimura, M. Kakizaki, S. Takagi, Nomiyama T.J. Schall, O. Yoshie, Cell 91, 521–530, (1997)Google Scholar
  11. 11.
    S. Jung, J. Aliberti, P. Graemmel, M.J. Sunshine, G.W. Kreutzberg, A. Sher, D.R. Littman, Mol. Cell Biol. 20, 4106–1114, (2000)PubMedCrossRefGoogle Scholar
  12. 12.
    A. Maho, A. Bensimon, G. Vassart, M. Parmentier, Cytogenet. Cell Genet. 87, 265–268, (1999)PubMedCrossRefGoogle Scholar
  13. 13.
    M.E. DeVries, H. Cao, J. Wang, L. Xu, A.A. Kelvin, L. Ran, L.A. Chau, J. Madrenas, R.A. Hegele, D.J. Kelvin, J. Biol. Chem. 278, 11985–11994, (2003)PubMedCrossRefGoogle Scholar
  14. 14.
    L.S. Mizoue, J.F. Bazan, E.C. Johnson, T.M. Handel, Biochemistry 38, 1402–1414, (1999)PubMedCrossRefGoogle Scholar
  15. 15.
    D.M. Hoover, L.S. Mizoue, T.M. Handel, J. Lubkowski, J. Biol. Chem. 275, 23187–23193, (2000)PubMedCrossRefGoogle Scholar
  16. 16.
    J.K. Harrison, A.M. Fong, P.H.W. Swain, S. Chen, Y-R.A. Yu, M.N. Salafranca, W.B. Greenleaf, T. Imai, D.D. Patel, J. Biol. Chem 276, 21632–21641, (2001)PubMedCrossRefGoogle Scholar
  17. 17.
    C. Combadiere, K. Salzwedel, E.D. Smith, H.L. Tiffany, E.A. Berger, P.M. Murphy, J. Biol. Chem. 273, 23799–23804, (1998)PubMedCrossRefGoogle Scholar
  18. 18.
    A. Garin, N. Tarantino, S. Faure, M. Daoudi, C. Lecureuil, A. Boudais, P. Debré, P. Deterre, C. Combadiere, J. Immunol. 171, 5305–5312, (2003)PubMedGoogle Scholar
  19. 19.
    D. Moatti, S. Faure, F. Fumeron, Mel-W. Amara, P. Seknadji, D.H. McDermott, P. Debre, M.C. Aumont, P.M. Murphy, D. de Prost, C. Combadiere, Blood 97, 1925–1928, (2001)PubMedCrossRefGoogle Scholar
  20. 20.
    S. Faure, L. Meyer, D. Costagliola, C. Vaneensberghe, E. Genin, B. Autran, J-F. Delfraissy, D.H. McDermott, P.M. Murphy, P. Debre, I. Theodorou, C. Combadiere, Science 287, 2274–2277, (2000)PubMedCrossRefGoogle Scholar
  21. 21.
    S. Faure, L. Meyer, E. Genin, P. Pellet, P. Debre, I. Theodorou, C. Combadiere, SEROCO Study Group. J. Acquir. Immune Defic. Syndr. 32, 335–337, (2003)CrossRefGoogle Scholar
  22. 22.
    T. Matthews, M. Salgo, M. Greenberg, J. Chung, R. DeMasi, D. Bolognesi, Nature Reviews/Drug Discovery 3, 215–225, (2004)CrossRefGoogle Scholar
  23. 23.
    D.H. McDermott, A.M. Fong, Q. Yang, J.M. Sechler, L.A. Cupples, M.N. Merrell P.W.F. Wilson R.B. D’Agostino, C.J. O’Donnell, D.D. Patel, P.M. Murphy, J. Clin. Invest. 111, 1241–1250, (2003)PubMedCrossRefGoogle Scholar
  24. 24.
    D.H. McDermott, J.S. Colla, C.A. Kleeberger, M. Plankey, P.S. Rosenberg, E.D. Smith, P.A. Zimmerman, C. Combadiere, S.F. Leitman, R.A. Kaslow, J.J. Goedert, E.A. Berger, T.R. O’Brien, P.M. Murphy, Science 290, 2031a, (2000)CrossRefGoogle Scholar
  25. 25.
    H. Hendel, C. Winkler, P. An, E. Roemer-Binns, G. Nelson, P. Haumont, S. O’Brien, K. Khalilli, D. Zagury, J. Rappaport, J.F. Zagury, J. Acquir. Immune Defic. Sundr. 26, 507–511, 2001Google Scholar
  26. 26.
    A. Foussat, L. Bouchet-Delbos, D. Berrebi, I. Durand-Gasselin, A. Coulomb-L’Hermine, R. Krzysiek, P. Galanaud, Y. Levy, D. Emilie, Blood 98, 1678–1686, (2001)PubMedCrossRefGoogle Scholar
  27. 27.
    A. Foussat, A. Coulomb-L’Hermine, J. Gosling, R. Krzysiek, I. Durand-Gasselin, T. Schall, A. Balian, Y. Richard, P. Galanaud, D. Emilie, Eur. J. Immunol. 30, 87–97, (2000)PubMedCrossRefGoogle Scholar
  28. 28.
    A.M. Fong, L.A. Robinson, D.A. Steeber, T.F. Tedder, O. Yoshie, T. Imai, D.D. Patel, J. Exp. Med. 188, 1413–1419, (1998)PubMedCrossRefGoogle Scholar
  29. 29.
    P. Fraticelli, M. Sironi, G. Bianchi, D. D’Ambrosio, C. Albanesi, A. Stoppacciaro, M. Chieppa, P. Allavena, L. Ruco, G. Girolomoni, F. Sinigaglia, A. Vecchi, A. Mantovani, J. Clin. Invest. 107, 1173–1181, (2001)PubMedCrossRefGoogle Scholar
  30. 30.
    M. Nishimura, H. Umehara, T. Nakayama, O. Yoneda, K. Hieshima, M. Kakizaki, N. Dohmae, O. Yoshie, T. Imai, J. Immunol. 168, 6173–6180, (2002)PubMedGoogle Scholar
  31. 31.
    B. Combadière, S. Faure B. Autran, P. Debré, C. Combadière, AIDS 17, 1279–1290, (2003)PubMedCrossRefGoogle Scholar
  32. 32.
    P. Ancuta, A. Moses, D. Gabuzda, Immunobiology 209, 11–20, (2004)PubMedCrossRefGoogle Scholar
  33. 33.
    E.J. Papadopoulos, D.J. Fitzhugh, C. Tkaczyk, A.M. Gilfillan, C. Sassetti, D.D. Metcalfe, S.T. Hwang, Eur. J. Immunol. 30, 2355–2361, (2000)PubMedCrossRefGoogle Scholar
  34. 34.
    E.J. Papadopoulos, C. Sassetti, H. Saeki, N. Yamada, T. Kawamura, D.J. Fitzhugh, M.A. Saraf, T. Schall, A. Blauvelt, S.D. Rosen, S.T. Hwang, Eur. J. Immunol. 29, 2551–2559, (1999)PubMedCrossRefGoogle Scholar
  35. 35.
    S. Dichmann, Y. Herouy, D. Purlis, H. Rheinen, P. Gebicke-Harter, J. Norgauer, Inflamm. Res. 50, 529–533, (2001)PubMedCrossRefGoogle Scholar
  36. 36.
    A.M. Fong, S.M. Alam, T. Imai, B. Haribabu, D.D. Patel, J. Biol. Chem. 277, 19418–19423, (2002)PubMedCrossRefGoogle Scholar
  37. 37.
    B. Kyewski, J. Derbrinski, Nat. Rev. Immunol. 4, 688–698, (2004)PubMedCrossRefGoogle Scholar
  38. 38.
    R. Medzhitov, C.A. Janeway Jr., Cell 91, 295–298, (1997)PubMedCrossRefGoogle Scholar
  39. 39.
    Y. Takahama, Nat. Rev. Immunol. 6, 127–135, (2006)PubMedCrossRefGoogle Scholar
  40. 40.
    V. Geenen, J-F. Poulin, M.L. Dion, H. Martens, E. Castermans, I. Hansenne, M. Moutschen, R.P. Sekaly, R. Cheynier, J. Endocrinol. 176, 305–311, (2003)PubMedCrossRefGoogle Scholar
  41. 41.
    M.L. Dion, J.F. Poulin, R. Bordi, M. Sylvestre, R. Corsini, N. Kettaf, A. Dalloul, M.R. Boulassel, P. Debre, J.P. Routy, Z. Grossman, R.P. Sekaly, R. Cheynier, Immunity 21, 757–768, (2004)PubMedCrossRefGoogle Scholar
  42. 42.
    D. Douek, Immunity 21, 744–745, (2004)PubMedGoogle Scholar
  43. 43.
    L. Andreoletti, N. Chomont, G. Gresenguet, M. Matta, J. de Dieu Longo, M.P. Carreno, A. Si-Mohamed, J. Legoff, M.D. Kazatchkine, L. Belec, J. Infect. Dis. 188, 549–554, (2003)PubMedCrossRefGoogle Scholar
  44. 44.
    G. Tirado, G. Jove, R. Kumar, R.J. Noel, E. Reyes, G. Sepulveda, Y. Yamamura, A. Kumar, Virology 324, 577–586, (2004)PubMedCrossRefGoogle Scholar
  45. 45.
    W. Berlier, T. Bourlet, P. Lawrence, H. Hamzeh, C. Lambert, C. Genin, B. Verrier, M.C. Dieu-Nosjean, B. Pozzetto, O. Delezay, J. Med. Virol. 77, 465–474, (2005)PubMedCrossRefGoogle Scholar
  46. 46.
    E.L. Delwart, J.I. Mullins, P. Gupta, G.H. Learn Jr., M. Holodniy, D. Katzenstein, B. Walker, M.K. Singh, J. Virol. 72, 617–623, (1998)PubMedGoogle Scholar
  47. 47.
    G. Nunnari, D. Leto, J. Sullivan, Y. Xu, K.E. Mehlman, J. Kulkosky, R.J. Pomerantz, AIDS Res. Hum. Retroviruses 21, 768–775, (2005)PubMedCrossRefGoogle Scholar
  48. 48.
    H. Cheroutre, L. Madakamutil, Nat. Rev. Immunol. 4, 290–300, (2004)PubMedCrossRefGoogle Scholar
  49. 49.
    A. Muehlhoefer, L.J. Saubermann, X. Gu, Luedtke-K. Heckenkamp, R. Xavier, R.S. Blumberg, D.K. Podolsky, R.P. MacDermott, H.C. Reinecker, J. Immunol. 164, 3368–3376, (2000)PubMedGoogle Scholar
  50. 50.
    J.H. Niess, S. Brand, X. Gu, L. Landsman, S. Jung, B.A. McCormick, J.M. Vyas, M. Boes, H.L. Ploegh, J.G. Fox, D.R. Littman, H.C. Reinecker, Science 307, 254–258, (2005)PubMedCrossRefGoogle Scholar
  51. 51.
    S. Mehandru, M.A. Poles, Tenner-K. Racz, A. Horowitz, A. Hurley, C. Hogan, D. Boden, P. Racz and M. Markowitz J. Exp. Med. 200, 761–770Google Scholar
  52. 52.
    J.M. Brenchley, T.W. Schacker, L.E. Ruff, D.A. Price, J.H. Taylor, G.J. Beilman, P.L. Nguyen, A. Khoruts, M. Larson, A.T. Haase, D.C. Douek, J. Exp. Med. 200, 749–759, (2004)PubMedCrossRefGoogle Scholar
  53. 53.
    R.S. Veazey, A.A. Lackner, J. Exp. Med. 200, 697–700, (2004)PubMedCrossRefGoogle Scholar
  54. 54.
    R.S. Veazey, M. DeMaria, L.V. Chalifoux, D.E. Shvetz, D.R. Pauley, H.L. Knight, M. Rosenzweig, R.P. Johnson, R.C. Desrosiers, A.A. Lackner, Science 280, 427–431, (1998)PubMedCrossRefGoogle Scholar
  55. 55.
    B. Pahar, A.A. Lackner, R.S. Veazey, Eur. J. Immunol. 36, 583–592, (2006)PubMedCrossRefGoogle Scholar
  56. 56.
    F. Gonzalez-Scarano, J. Martin-Garcia, Nat. Rev. Immunol. 5, 69–81, (2005)PubMedCrossRefGoogle Scholar
  57. 57.
    O. Meucci, A. Fatatis, A.A. Simen, R.J. Miller, Proc. Natl. Acad. Sci. USA 97, 8075–8080, (2000)PubMedCrossRefGoogle Scholar
  58. 58.
    O. Meucci, A. Fatatis, A.A. Simon, T.J. Bushell, P.W. Gray, R.J. Miller, Proc. Natl. Sci. USA 95, 14500–14505, (1998)CrossRefGoogle Scholar
  59. 59.
    J.K. Harrison, Y. Jiang, S. Chen, Y. Xia, D. Maciejewski, R.K. McNamara, W.J. Streit M.N. Salafranca, S. Adhikara, D.A. Thompson, P. Botti, K.B. Bacon, L. Feng, Proc. Natl. Acad. Sci. USA 95, 10896–10901, (1998)PubMedCrossRefGoogle Scholar
  60. 60.
    K. Hatori, A. Nagai, R. Heisel, J.K. Ryu, S.U. Kim, J. Neuroscience Res. 69, 418–426, (2002)CrossRefGoogle Scholar
  61. 61.
    D. Erichsen, A.L. Lopez, H. Peng, D. Niemann, C. Williams, M. Bauer, S. Morgello, R.L. Cotter, L.A. Ryan, A. Ghorpade, H.E. Gendelman, J. Zheng, J. Neuroimmunology 138, 144–155, (2003)CrossRefGoogle Scholar
  62. 62.
    G.D. Kanmogne, C. Primeaux, P. Grammas, J. Neuropathol. Exp. Neurol. 64, 498–505, (2005)PubMedGoogle Scholar
  63. 63.
    S.B. Oh, P.B. Tran, S.E. Gillard, R.W. Hurley, D.L. Hammond, R.J. Miller, J. Neurosci. 21, 5027–5035, (2001)PubMedGoogle Scholar
  64. 64.
    K.A. Walsh, J.F. Megyesi, J.X. Wilson, J. Crukley, V.E. Laubach, R.R. Hammond, J. Neuroinflammation 1, 8, (2004)PubMedCrossRefGoogle Scholar
  65. 65.
    L.S. Mizoue, J.F. Bazan, E.C. Johnson, T.M. Handel, Biochemistry 38, 1402–1414, (1999)PubMedCrossRefGoogle Scholar
  66. 66.
    A. Inoue, H. Hasegawa, M. Kohno, M.R. Ito, M. Terado, T. Imai, O. Yoshie, M. Nose, S. Fujita, Arthritis Rheum. 52, 1522–1533, (2005)PubMedCrossRefGoogle Scholar
  67. 67.
    H. Hasegawa, M. Kohno, M. Sasaki, A. Inoue, M.R. Ito, M. Terado, K. Hieshima, H. Maruyama, J.I. Miyazaki, O. Yoshie, M. Nose, S. Fujita, Arthritis Rheum. 48, 2555–2566, (2003)PubMedCrossRefGoogle Scholar
  68. 68.
    C.N. Davis, V. Zujovic, J.K. Harrison, Mol. Pharmacol. 66, 1431–1439, (2004)PubMedCrossRefGoogle Scholar
  69. 69.
    M.P. Crump, E. Elisseeva, J.H. Gong, I. Clark-Lewis, B.D. Sykes, FEBS Lett. 489, 171–175, (2001)PubMedCrossRefGoogle Scholar
  70. 70.
    S. Chen, K.B. Bacon, L. Li, G.E. Garcia, Y. Xia, D. Lo, D.A. Thompson, M.A. Siani, T. Yamamoto, J.K. Harrison, L. Feng, J. Exp. Med. 188, 193–198, (1998)PubMedCrossRefGoogle Scholar
  71. 71.
    A. Demissie, M. Abebe, A. Aseffa, G. Rook, H. Fletcher, A. Zumla, K. Weldingh, I. Brock, P. Andersen, T.M. Doherty, VACSEL study group, J. Immunol. 172, 6938–6943, (2004)Google Scholar
  72. 72.
    G.T. Seah, P.S. Gao, J.M. Hopkin, G.A.M. Rook, Am. J. Respir. Crit. Care Med. 164, 1016–1018, (2001)PubMedGoogle Scholar
  73. 73.
    G. Avensa, J. Punnonen, B.G. Cocks, de Waal, R.W. Malefyt, F. Vega Jr., S.M. Zurawski, G. Zurawski, de J.E. Vries, J. Exp. Med. 178, 2213–2218, (1993)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  1. 1.Department of Molecular Virology, Faculty of MedicineThe Hebrew University of JerusalemJerusalemIsrael

Personalised recommendations