Attachment of human immunodeficiency virus to cells and its inhibition

  • Stefan Pöhlmann
  • Michel J. Tremblay
Part of the Milestones in Drug Therapy book series (MDT)


The entry of enveloped viruses involves virus adsorption followed by close apposition of the viral and plasma membranes. This multistep process is initiated by specific binding interactions between glycoproteins in the viral envelope and appropriate receptors on the cell surface. In the case of HIV-1, attachment of virions to the cell surface is attributed to a high affinity interaction between envelope spike glycoproteins (Env, composed of the surface protein gp120 and the transmembrane protein gp41) and a complex made of the primary CD4 receptor and a seven-transmembrane co-receptor (e.g., CXCR4 or CCR5) (reviewed in [1]). Then a chain of dynamic events take place that enable the viral nucleocapsid to penetrate within the target cell following the destabilization of membrane microenvironment and the formation of a fusion pore.


Human Immunodeficiency Virus Simian Immunodeficiency Virus Major Histocompatibility Complex Presentation 
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  1. 1.
    Clapham PR, McKnight A (2002) Cell surface receptors, virus entry and tropism of primate lentiviruses. J Gen Virol 83: 1809–1829PubMedGoogle Scholar
  2. 2.
    Ugolini S, Mondor I, Sattentau QJ (1999) HIV-1 attachment: another look. Trends Microbiol 7: 144–149PubMedCrossRefGoogle Scholar
  3. 3.
    Mondor I, Ugolini S, Sattentau QJ (1998) Human immunodeficiency virus type 1 attachment to HeLa CD4 cells is CD4 independent and gp120 dependent and requires cell surface heparans. J Virol 72: 3623–3634PubMedGoogle Scholar
  4. 4.
    Saphire AC, Bobardt MD, Zhang Z, David G, Gallay PA (2001) Syndecans serve as attachment receptors for human immunodeficiency virus type 1 on macrophages. J Virol 75: 9187–9200PubMedCrossRefGoogle Scholar
  5. 5.
    Bobardt MD, Saphire AC, Hung HC, Yu X, Van der Schueren B, Zhang Z, David G, Gallay PA (2003) Syndecan captures, protects, and transmits HIV to T lymphocytes. Immunity 18: 27–39PubMedCrossRefGoogle Scholar
  6. 6.
    Fantini J, Cook DG, Nathanson N, Spitalnik SL, Gonzalez-Scarano F (1993) Infection of colonic epithelial cell lines by type 1 human immunodeficiency virus is associated with cell surface expression of galactosylceramide, a potential alternative gp120 receptor. Proc Natl Acad Sci USA 90: 2700–2704PubMedCrossRefGoogle Scholar
  7. 7.
    Harouse JM, Bhat S, Spitalnik SL, Laughlin M, Stefano K, Silberberg DH, Gonzalez-Scarano F (1991) Inhibition of entry of HIV-1 in neural cell lines by antibodies against galactosyl ceramide. Science 253: 320–323PubMedCrossRefGoogle Scholar
  8. 8.
    Seddiki N, Ramdani A, Saffar L, Portoukalian J, Gluckman JC, Gattegno L (1994) A monoclonal antibody directed to sulfatide inhibits the binding of human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein to macrophages but not their infection by the virus. Biochim Biophys Acta 1225: 289–296PubMedGoogle Scholar
  9. 9.
    Larkin M, Childs RA, Matthews TJ, Thiel S, Mizuochi T, Lawson AM, Savill JS, Haslett C, Diaz R, Feizi T (1989) Oligosaccharide-mediated interactions of the envelope glycoprotein gp120 of HIV-1 that are independent of CD4 recognition. AIDS 3: 793–798PubMedCrossRefGoogle Scholar
  10. 10.
    Geijtenbeek TB, Kwon DS, Torensma R, van Vliet SJ, van Duijnhoven GC, Middel J, Cornelissen IL, Nottet HS, KewalRamani VN, Littman DR et al. (2000) DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell 100: 587–597PubMedCrossRefGoogle Scholar
  11. 11.
    Pöhlmann S, Soilleux EJ, Baribaud F, Leslie GJ, Morris LS, Trowsdale J, Lee B, Coleman N, Doms RW (2001) DC-SIGNR, a DC-SIGN homologue expressed in endothelial cells, binds to human and simian immunodeficiency viruses and activates infection in trans. Proc Natl Acad Sci USA 98: 2670–2675PubMedCrossRefGoogle Scholar
  12. 12.
    Tremblay MJ, Fortin J-F, Cantin R (1998) The acquisition of host-encoded proteins by nascent HIV-1. Immunol Today 19: 346–351PubMedCrossRefGoogle Scholar
  13. 13.
    Ott DE (2002) Potential roles of cellular proteins in HIV-1. Rev Med Virol 12: 359–374PubMedCrossRefGoogle Scholar
  14. 14.
    Ott DE (1997) Cellular proteins in HIV virions. Rev Med Virol 7: 167–180PubMedCrossRefGoogle Scholar
  15. 15.
    Cantin R, Methot S, Tremblay MJ (2005) Plunder and stowaways: incorporation of cellular proteins by enveloped viruses. J Virol 79: 6577–6587PubMedCrossRefGoogle Scholar
  16. 16.
    Cantin R, Fortin J-F, Lamontagne G, Tremblay M (1997) The acquisition of host major histocompatibility complex class II glycoproteins by human immunodeficiency virus type 1 accelerates the process of virus entry and infection in human T-lymphoid cells. Blood 90: 1091–1100PubMedGoogle Scholar
  17. 17.
    Cantin R, Martin G, Tremblay MJ (2001) A novel virus capture assay reveals a differential acquisition of host HLA-DR by clinical isolates of human immunodeficiency virus type 1 expanded in primary human cells depending on the nature of producing cells and the donor source. J Gen Virol 82: 2979–2987PubMedGoogle Scholar
  18. 18.
    Orentas RJ, Hildreth JEK (1993) Association of host cell surface adhesion receptors and other membrane proteins with HIV and SIV. AIDS Res Hum Retroviruses 9: 1157–1165PubMedGoogle Scholar
  19. 19.
    Rossio JL, Bess J, Henderson LE, Cresswell P, Arthur LO (1995) HLA class II on HIV particles is functional in superantigen presentation to human T cells: Implications for HIV pathogenesis. AIDS Res Hum Retroviruses 11: 1433–1439PubMedGoogle Scholar
  20. 20.
    Liao Z, Roos JW, Hildreth JE (2000) Increased infectivity of HIV type 1 particles bound to cell surface and solid-phase ICAM-1 and VCAM-1 through acquired adhesion molecules LFA-1 and VLA-4. AIDS Res Hum Retroviruses 16: 355–366PubMedCrossRefGoogle Scholar
  21. 21.
    Guo MML, Hildreth JEK (1995) HIV acquires functional adhesion receptors from host cells. AIDS Res Hum Retroviruses 11: 1007–1013PubMedCrossRefGoogle Scholar
  22. 22.
    Fortin J-F, Cantin R, Tremblay M (1998) T cells expressing activated LFA-1 are more susceptible to infection with human immunodeficiency virus type 1 particles bearing host-encoded ICAM-1. J Virol 72: 2105–2112PubMedGoogle Scholar
  23. 23.
    Rizzuto CD, Sodroski JG (1997) Contribution of virion ICAM-1 to human immunodeficiency virus infectivity and sensitivity to neutralization. J Virol 71: 4847–4851PubMedGoogle Scholar
  24. 24.
    Montefiori DC, Cornell RJ, Zhou JY, Zhou JT, Hirsch VM, Johnson PR (1994) Complement control proteins, CD46, CD55, and CD59, as common surface constituents of human and simian immunodeficiency viruses and possible targets for vaccine protection. Virology 205: 82–92PubMedCrossRefGoogle Scholar
  25. 25.
    Giguère J-F, Paquette JS, Bounou S, Cantin R, Tremblay MJ (2002) New insights into the functionality of a virion-anchored host cell membrane protein: CD28 versus HIV type 1. J Immunol 169: 2762–2771PubMedGoogle Scholar
  26. 26.
    Bounou S, Dumais N, Tremblay MJ (2001) Attachment of human immunodeficiency virus-1 (HIV-1) particles bearing host-encoded B7-2 proteins leads to nuclear factor-kB-and nuclear factor of activated T cells-dependent activation of HIV-1 long terminal repeat transcription. J Biol Chem 276: 6359–6369PubMedCrossRefGoogle Scholar
  27. 27.
    Cantin R, Fortin J-F, Tremblay M (1996) The amount of host HLA-DR proteins acquired by HIV-1 is virus strain-and cell type-specific. Virology 218: 372–381PubMedCrossRefGoogle Scholar
  28. 28.
    Capobianchi MR, Fais S, Castilletti C, Gentile M, Ameglio F, Dianzani F (1994) A simple and reliable method to detect cell membrane proteins on infectious human immunodeficiency virus type 1 particles. J Infect Dis 169: 886–889PubMedGoogle Scholar
  29. 29.
    Frank I, Stoiber H, Godar S, Stockinger H, Steindl F, Katinger HWD, Dierich MP (1996) Acquisition of host cell-surface-derived molecules by HIV-1. AIDS 10: 1611–1620PubMedGoogle Scholar
  30. 30.
    Roberts BD, Butera ST (1999) Host protein incorporation is conserved among diverse HIV-1 subtypes. AIDS 13: 425–427PubMedCrossRefGoogle Scholar
  31. 31.
    Bounou S, Leclerc JE, Tremblay MJ (2002) Presence of host ICAM-1 in laboratory and clinical strains of human immunodeficiency virus type 1 increases virus infectivity and CD4(+)-T-cell depletion in human lymphoid tissue, a major site of replication in vivo. J Virol 76: 1004–1014PubMedGoogle Scholar
  32. 32.
    Bastiani L, Laal S, Kim M, Zolla-Pazner S (1997) Host cell-dependent alterations in envelope components of human immunodeficiency virus type 1 virions. J Virol 71: 3444–3450PubMedGoogle Scholar
  33. 33.
    Lawn SD, Roberts BD, Griffin GE, Folks TM, Butera ST (2000) Cellular compartments of human immunodeficiency virus type 1 replication in vivo: determination by presence of virion-associated host proteins and impact of opportunistic infection. J Virol 74: 139–145PubMedCrossRefGoogle Scholar
  34. 34.
    Saarloos M-N, Sullivan BL, Czerniewski MA, Parameswar KD, Spear GT (1997) Detection of HLA-DR associated with monocytotropic, primary, and plasma isolates of human immunodeficiency virus type 1. J Virol 71: 1640–1643PubMedGoogle Scholar
  35. 35.
    Trowbridge IS (1991) CD45: A prototype for transmembrane protein tyrosine phosphatases. J Biol Chem 26: 23517–23520Google Scholar
  36. 36.
    Esser MT, Graham DR, Coren LV, Trubey CM, Bess JW, Arthur LO, Ott DE, Lifson JD (2001) Differential incorporation of CD45, CD80 (B7-1), CD86 (B7-2), and major histocompatibility complex class I and II molecules into human immunodeficiency virus type 1 virions and microvesicles: implications for viral pathogenesis and immune regulation. J Virol 75: 6173–6182PubMedCrossRefGoogle Scholar
  37. 37.
    Lallos LB, Laal S, Hoxie JA, Zolla-Pazner S, Bandres JC (1999) Exclusion of HIV coreceptors CXCR4, CCR5, and CCR3 from the HIV envelope. AIDS Res Hum Retroviruses 15: 895–897PubMedCrossRefGoogle Scholar
  38. 38.
    Frank I, Kacani L, Stoiber H, Stossel H, Spruth M, Steindl F, Romani N, Dierich MP (1999) Human immunodeficiency virus type 1 derived from cocultures of immature dendritic cells with autologous T cells carries T-cell-specific molecules on its surface and is highly infectious. J Virol 73: 3449–3454PubMedGoogle Scholar
  39. 39.
    Arthur LO, Bess JWJ, Sowder II RC, Benveniste RE, Mann DL, Cherman J-C, Henderson LE (1992) Cellular proteins bound to immunodeficiency viruses: Implication for pathogenesis and vaccines. Science 258: 1935–1938PubMedCrossRefGoogle Scholar
  40. 40.
    Chertova E, Bess JW Jr, Crise BJ, Sowder IR, Schaden TM, Hilburn JM, Hoxie JA, Benveniste RE, Lifson JD, Henderson LE et al. (2002) Envelope glycoprotein incorporation, not shedding of surface envelope glycoprotein (gp120/SU), Is the primary determinant of SU content of purified human immunodeficiency virus type 1 and simian immunodeficiency virus. J Virol 76: 5315–5325PubMedCrossRefGoogle Scholar
  41. 41.
    Beauséjour Y, Tremblay MJ (2004) Envelope glycoproteins are not required for insertion of host ICAM-1 into human immunodeficiency virus type 1 and ICAM-1-bearing viruses are still infectious despite a suboptimal level of trimeric envelope proteins. Virology 324: 165–172PubMedCrossRefGoogle Scholar
  42. 42.
    Beauséjour Y, Tremblay MJ (2004) Interaction between the cytoplasmic domain of ICAM-1 and Pr55Gag leads to acquisition of host ICAM-1 by human immunodeficiency virus type 1. J Virol 78: 11916–11925PubMedCrossRefGoogle Scholar
  43. 43.
    Cantin R, Fortin J-F, Lamontagne G, Tremblay M (1997) The presence of host-derived HLA-DR1 on human immunodeficiency virus type 1 increases viral infectivity. J Virol 71: 1922–1930PubMedGoogle Scholar
  44. 44.
    Fortin J-F, Cantin R, Lamontagne G, Tremblay M (1997) Host-derived ICAM-1 glycoproteins incorporated on human immunodeficiency virus type 1 are biologically active and enhances viral infectivity. J Virol 71: 3588–3596PubMedGoogle Scholar
  45. 45.
    Fortin JF, Barbeau B, Hedman H, Lundgren E, Tremblay MJ (1999) Role of the leukocyte function antigen-1 conformational state in the process of human immunodeficiency virus type 1-mediated syncytium formation and virus infection. Virology 257: 228–238PubMedCrossRefGoogle Scholar
  46. 46.
    Tardif MR, Tremblay MJ (2005) Regulation of LFA-1 activity through cytoskeleton remodeling and signaling components modulates the efficiency of HIV type-1 entry in activated CD4+ T lymphocytes. J Immunol 175: 926–935PubMedGoogle Scholar
  47. 47.
    Tardif MR, Tremblay MJ (2003) Presence of host ICAM-1 in human immunodeficiency virus type 1 virions increases productive infection of CD4+ T lymphocytes by favoring cytosolic delivery of viral material. J Virol 77: 12299–12309PubMedCrossRefGoogle Scholar
  48. 48.
    Tardif MR, Tremblay MJ (2005) LFA-1 is a key determinant for preferential infection of memory CD4+ T cells by human immunodeficiency virus type 1. J Virol 79: 13714–13724PubMedCrossRefGoogle Scholar
  49. 49.
    Giguère JF, Paquette J-S, Bounou S, Cantin R, Tremblay MJ (2002) New insights into the functionality of a virion-anchored host cell membrane protein: CD28 vs HIV type 1. J Immunol 169: 2762–2771PubMedGoogle Scholar
  50. 50.
    Giguère J-F, Bounou S, Paquette JS, Madrenas J, Tremblay MJ (2004) Insertion of host-derived costimulatory molecules CD80 (B7.1) and CD86 (B7.2) into human immunodeficiency virus type 1 affects the virus life cycle. J Virol 78: 6222–6232PubMedCrossRefGoogle Scholar
  51. 51.
    Fortin J-F, Cantin R, Bergeron MG, Tremblay MJ (2000) Interaction between virion-bound host ICAM-1 and the high affinity state of LFA-1 on target cells renders R5 and X4 isolates of HIV-1 more refractory to neutralization. Virology 268: 493–503PubMedCrossRefGoogle Scholar
  52. 52.
    Losier M, Fortin JF, Cantin R, Bergeron MG, Tremblay MJ (2003) Virion-bound ICAM-1 and activated LFA-1: a combination of factors conferring resistance to neutralization by sera from human immunodeficiency virus type 1-infected individuals independently of the disease status and phase. Clin Immunol 108: 111–118PubMedCrossRefGoogle Scholar
  53. 53.
    Beauséjour Y, Tremblay MJ (2004) Susceptibility of HIV type 1 to the fusion inhibitor T-20 is reduced on insertion of host intercellular adhesion molecule 1 in the virus membrane. J Infect Dis 190: 894–902PubMedCrossRefGoogle Scholar
  54. 54.
    Arthur LO, Bess JWJ, Urban RG, Strominger JL, Morton WR, Mann DL, Henderson LE, Benveniste RE (1995) Macaques immunized with HLA-DR are protected from challenge with simian immunodeficiency virus. J Virol 69: 3117–3124PubMedGoogle Scholar
  55. 55.
    Chan WL, Rodgers A, Grief C, Almond N, Ellis S, Flanagan B, Silvera P, Bootman J, Stott J, Kent K et al. (1995) Immunization with class I histocompatibility leukocyte antigen can protect macaques against challenge infection with SIVmac-32H. AIDS 9: 223–228PubMedCrossRefGoogle Scholar
  56. 56.
    Giguère J-F, Tremblay MJ (2004) Statin compounds reduce human immunodeficiency virus type 1 replication by preventing the interaction between virion-associated host intercellular adhesion molecule 1 and its natural cell surface ligand LFA-1. J Virol 78: 12062–12065PubMedCrossRefGoogle Scholar
  57. 57.
    del Real G, Jimenez-Baranda S, Mira E, Lacalle RA, Lucas P, Gomez-Mouton C, Alegret M, Pena JM, Rodriguez-Zapata M, Alvarez-Mon M et al. (2004) Statins inhibit HIV-1 infection by down-regulating Rho activity. J Exp Med 200: 541–547PubMedCrossRefGoogle Scholar
  58. 58.
    Shattock RJ, Moore JP (2003) Inhibiting sexual transmission of HIV-1 infection. Nat Rev Microbiol 1: 25–34PubMedCrossRefGoogle Scholar
  59. 59.
    Steinman RM, Granelli-Piperno A, Pope M, Trumpfheller C, Ignatius R, Arrode G, Racz P, Tenner-Racz K (2003) The interaction of immunodeficiency viruses with dendritic cells. Curr Top Microbiol Immunol 276: 1–30PubMedGoogle Scholar
  60. 60.
    Curtis BM, Scharnowske S, Watson AJ (1992) Sequence and expression of a membrane-associated C-type lectin that exhibits CD4-independent binding of human immunodeficiency virus envelope glycoprotein gp120. Proc Natl Acad Sci USA 89: 8356–8360PubMedCrossRefGoogle Scholar
  61. 61.
    Kwon DS, Gregorio G, Bitton N, Hendrickson WA, Littman DR (2002) DC-SIGN-mediated internalization of HIV is required for trans-enhancement of T cell infection. Immunity 16: 135–144PubMedCrossRefGoogle Scholar
  62. 62.
    Geijtenbeek TB, Engering A, Van Kooyk Y (2002) DC-SIGN, a C-type lectin on dendritic cells that unveils many aspects of dendritic cell biology. J Leukoc Biol 71: 921–931PubMedGoogle Scholar
  63. 63.
    Geijtenbeek TB, Krooshoop DJ, Bleijs DA, van Vliet SJ, van Duijnhoven GC, Grabovsky V, Alon R, Figdor CG, van Kooyk Y (2000) DC-SIGN-ICAM-2 interaction mediates dendritic cell trafficking. Nat Immunol 1: 353–357PubMedCrossRefGoogle Scholar
  64. 64.
    Geijtenbeek TB, Torensma R, van Vliet SJ, van Duijnhoven GC, Adema GJ, van Kooyk Y, Figdor CG (2000) Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. Cell 100: 575–585PubMedCrossRefGoogle Scholar
  65. 65.
    Snyder GA, Ford J, Torabi-Parizi P, Arthos JA, Schuck P, Colonna M, Sun PD (2005) Characterization of DC-SIGN/R interaction with human immunodeficiency virus type 1 gp120 and ICAM molecules favors the receptor’s role as an antigen-capturing rather than an adhesion receptor. J Virol 79: 4589–4598PubMedCrossRefGoogle Scholar
  66. 66.
    Wu L, Bashirova AA, Martin TD, Villamide L, Mehlhop E, Chertov AO, Unutmaz D, Pope M, Carrington M, KewalRamani VN (2002) Rhesus macaque dendritic cells efficiently transmit primate lentiviruses independently of DC-SIGN. Proc Natl Acad Sci USA 99: 1568–1573PubMedCrossRefGoogle Scholar
  67. 67.
    Gummuluru S, Rogel M, Stamatatos L, Emerman M (2003) Binding of human immunodeficiency virus type 1 to immature dendritic cells can occur independently of DC-SIGN and mannose binding C-type lectin receptors via a cholesterol-dependent pathway. J Virol 77: 12865–12874PubMedCrossRefGoogle Scholar
  68. 68.
    Granelli-Piperno A, Pritsker A, Pack M, Shimeliovich I, Arrighi JF, Park CG, Trumpfheller C, Piguet V, Moran TM, Steinman RM (2005) Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin/CD209 is abundant on macrophages in the normal human lymph node and is not required for dendritic cell stimulation of the mixed leukocyte reaction. J Immunol 175: 4265–4273PubMedGoogle Scholar
  69. 69.
    Baribaud F, Pöhlmann S, Leslie G, Mortari F, Doms RW (2002) Quantitative expression and virus transmission analysis of DC-SIGN on monocyte-derived dendritic cells. J Virol 76: 9135–9142PubMedCrossRefGoogle Scholar
  70. 70.
    Trumpfheller C, Park CG, Finke J, Steinman RM, Granelli-Piperno A (2003) Cell type-dependent retention and transmission of HIV-1 by DC-SIGN. Int Immunol 15: 289–298PubMedCrossRefGoogle Scholar
  71. 71.
    Wu L, Martin TD, Vazeux R, Unutmaz D, KewalRamani VN (2002) Functional evaluation of DCSIGN monoclonal antibodies reveals DC-SIGN interactions with ICAM-3 do not promote human immunodeficiency virus type 1 transmission. J Virol 76: 5905–5914PubMedCrossRefGoogle Scholar
  72. 72.
    Turville SG, Cameron PU, Handley A, Lin G, Pöhlmann S, Doms RW, Cunningham AL (2002) Diversity of receptors binding HIV on dendritic cell subsets. Nat Immunol 3: 975–983PubMedCrossRefGoogle Scholar
  73. 73.
    Wu L, Martin TD, Carrington M, KewalRamani VN (2004) Raji B cells, misidentified as THP-1 cells, stimulate DC-SIGN-mediated HIV transmission. Virology 318: 17–23PubMedCrossRefGoogle Scholar
  74. 74.
    Turville SG, Santos JJ, Frank I, Cameron PU, Wilkinson J, Miranda-Saksena M, Dable J, Stossel H, Romani N, Piatak M Jr et al. (2004) Immunodeficiency virus uptake, turnover, and 2-phase transfer in human dendritic cells. Blood 103: 2170–2179PubMedCrossRefGoogle Scholar
  75. 75.
    Nobile C, Petit C, Moris A, Skrabal K, Abastado JP, Mammano F, Schwartz O (2005) Covert human immunodeficiency virus replication in dendritic cells and in DC-SIGN-expressing cells promotes long-term transmission to lymphocytes. J Virol 79: 5386–5399PubMedCrossRefGoogle Scholar
  76. 76.
    Burleigh L, Lozach PY, Schiffer C, Staropoli I, Pezo V, Porrot F, Canque B, Virelizier JL, Arenzana-Seisdedos F, Amara A (2006) Infection of dendritic cells (DCs), not DC-SIGN-mediated internalization of human immunodeficiency virus, is required for long-term transfer of virus to T cells. J Virol 80: 2949–2957PubMedCrossRefGoogle Scholar
  77. 77.
    Moris A, Nobile C, Buseyne F, Porrot F, Abastado JP, Schwartz O (2004) DC-SIGN promotes exogenous MHC-I-restricted HIV-1 antigen presentation. Blood 103: 2648–2654PubMedCrossRefGoogle Scholar
  78. 78.
    Moris A, Pajot A, Blanchet F, Guivel-Benhassine F, Salcedo M, Schwartz O (2006) Dendritic cells and HIV-specific CD4+ T cells: HIV antigen presentation, T cell activation, viral transfer. Blood 108: 1643–1651PubMedCrossRefGoogle Scholar
  79. 79.
    Krutzik SR, Tan B, Li H, Ochoa MT, Liu PT, Sharfstein SE, Graeber TG, Sieling PA, Liu YJ, Rea TH et al. (2005) TLR activation triggers the rapid differentiation of monocytes into macrophages and dendritic cells. Nat Med 11: 653–660PubMedCrossRefGoogle Scholar
  80. 80.
    Jameson B, Baribaud F, Pöhlmann S, Ghavimi D, Mortari F, Doms RW, Iwasaki A (2002) Expression of DC-SIGN by dendritic cells of intestinal and genital mucosae in humans and rhesus macaques. J Virol 76: 1866–1875PubMedCrossRefGoogle Scholar
  81. 81.
    Soilleux EJ, Morris LS, Leslie G, Chehimi J, Luo Q, Levroney E, Trowsdale J, Montaner LJ, Doms RW, Weissman D et al. (2002) Constitutive and induced expression of DC-SIGN on dendritic cell and macrophage subpopulations in situ and in vitro. J Leukoc Biol 71: 445–457PubMedGoogle Scholar
  82. 82.
    Arrighi JF, Pion M, Wiznerowicz M, Geijtenbeek TB, Garcia E, Abraham S, Leuba F, Dutoit V, Ducrey-Rundquist O, van Kooyk Y et al. (2004) Lentivirus-mediated RNA interference of DCSIGN expression inhibits human immunodeficiency virus transmission from dendritic cells to T cells. J Virol 78: 10848–10855PubMedCrossRefGoogle Scholar
  83. 83.
    Arrighi JF, Pion M, Garcia E, Escola JM, van Kooyk Y, Geijtenbeek TB, Piguet V (2004) DCSIGN-mediated infectious synapse formation enhances X4 HIV-1 transmission from dendritic cells to T cells. J Exp Med 200: 1279–1288PubMedCrossRefGoogle Scholar
  84. 84.
    McDonald D, Wu L, Bohks SM, KewalRamani VN, Unutmaz D, Hope TJ (2003) Recruitment of HIV and its receptors to dendritic cell-T cell junctions. Science 300: 1295–1297PubMedCrossRefGoogle Scholar
  85. 85.
    Hu Q, Frank I, Williams V, Santos JJ, Watts P, Griffin GE, Moore JP, Pope M, Shattock RJ (2004) Blockade of attachment and fusion receptors inhibits HIV-1 infection of human cervical tissue. J Exp Med 199: 1065–1075PubMedCrossRefGoogle Scholar
  86. 86.
    Boukour S, Masse JM, Benit L, Dubart-Kupperschmitt A, Cramer EM (2006) Lentivirus degradation and DC-SIGN expression by human platelets and megakaryocytes. J Thromb Haemost 4: 426–435PubMedCrossRefGoogle Scholar
  87. 87.
    Chaipan C, Soilleux EJ, Simpson P, Hofmann H, Gramberg T, Marzi A, Geier M, Stewart EA, Eisemann J, Steinkasserer A et al. (2006) DC-SIGN and CLEC-2 mediate human immunodeficiency virus type 1 capture by platelets. J Virol 80:8951–60PubMedCrossRefGoogle Scholar
  88. 88.
    Rappocciolo G, Piazza P, Fuller CL, Reinhart TA, Watkins SC, Rowe DT, Jais M, Gupta P, Rinaldo CR (2006) DC-SIGN on B lymphocytes is required for transmission of HIV-1 to T lymphocytes. PLoS Pathog 2: e70PubMedCrossRefGoogle Scholar
  89. 89.
    Martin MP, Lederman MM, Hutcheson HB, Goedert JJ, Nelson GW, van Kooyk Y, Detels R, Buchbinder S, Hoots K, Vlahov D et al. (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: 14053–14056PubMedCrossRefGoogle Scholar
  90. 90.
    Liu H, Hwangbo Y, Holte S, Lee J, Wang C, Kaupp N, Zhu H, Celum C, Corey L, McElrath MJ et al. (2004) Analysis of genetic polymorphisms in CCR5, CCR2, stromal cell-derived factor-1, RANTES, and dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin in seronegative individuals repeatedly exposed to HIV-1. J Infect Dis 190: 1055–1058PubMedCrossRefGoogle Scholar
  91. 91.
    Bashirova AA, Geijtenbeek TB, van Duijnhoven GC, van Vliet SJ, Eilering JB, Martin MP, Wu L, Martin TD, Viebig N, Knolle PA et al. (2001) A dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein is highly expressed on human liver sinusoidal endothelial cells and promotes HIV-1 infection. J Exp Med 193: 671–678PubMedCrossRefGoogle Scholar
  92. 92.
    Jeffers SA, Tusell SM, Gillim-Ross L, Hemmila EM, Achenbach JE, Babcock GJ, Thomas WD Jr, Thackray LB, Young MD, Mason RJ et al. (2004) CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus. Proc Natl Acad Sci USA 101: 15748–15753PubMedCrossRefGoogle Scholar
  93. 93.
    Chan VS, Chan KY, Chen Y, Poon LL, Cheung AN, Zheng B, Chan KH, Mak W, Ngan HY, Xu X et al. (2006) Homozygous L-SIGN (CLEC4M) plays a protective role in SARS coronavirus infection. Nat Genet 38: 38–46PubMedCrossRefGoogle Scholar
  94. 94.
    Liu H, Hladik F, Andrus T, Sakchalathorn P, Lentz GM, Fialkow MF, Corey L, McElrath MJ, Zhu T (2005) Most DC-SIGNR transcripts at mucosal HIV transmission sites are alternatively spliced isoforms. Eur J Hum Genet 13: 707–715PubMedCrossRefGoogle Scholar
  95. 95.
    Steffan AM, Lafon ME, Gendrault JL, Schweitzer C, Royer C, Jaeck D, Arnaud JP, Schmitt MP, Aubertin AM, Kirn A (1992) Primary cultures of endothelial cells from the human liver sinusoid are permissive for human immunodeficiency virus type 1. Proc Natl Acad Sci USA 89: 1582–1586PubMedCrossRefGoogle Scholar
  96. 96.
    Housset C, Lamas E, Brechot C (1990) Detection of HIV1 RNA and p24 antigen in HIV1-infected human liver. Res Virol 141: 153–159PubMedCrossRefGoogle Scholar
  97. 97.
    Housset C, Lamas E, Courgnaud V, Boucher O, Girard PM, Marche C, Brechot C (1993) Presence of HIV-1 in human parenchymal and non-parenchymal liver cells in vivo. J Hepatol 19: 252–258PubMedCrossRefGoogle Scholar
  98. 98.
    Lichterfeld M, Nischalke HD, van Lunzen J, Sohne J, Schmeisser N, Woitas R, Sauerbruch T, Rockstroh JK, Spengler U (2003) The tandem-repeat polymorphism of the DC-SIGNR gene does not affect the susceptibility to HIV infection and the progression to AIDS. Clin Immunol 107: 55–59PubMedCrossRefGoogle Scholar
  99. 99.
    Liu H, Carrington M, Wang C, Holte S, Lee J, Greene B, Hladik F, Koelle DM, Wald A, Kurosawa K et al. (2006) Repeat-region polymorphisms in the gene for the dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin-related molecule: effects on HIV-1 susceptibility. J Infect Dis 193: 698–702PubMedCrossRefGoogle Scholar
  100. 100.
    Guo Y, Atkinson CE, Taylor ME, Drickamer K (2006) All but the shortest polymorphic forms of the viral receptor DC-SIGNR assemble into stable homo-and heterotetramers. J Biol Chem 281: 16794–16798PubMedCrossRefGoogle Scholar
  101. 101.
    Gramberg T, Zhu T, Chaipan C, Marzi A, Liu H, Wegele A, Andrus T, Hofmann H, Pöhlmann S (2006) Impact of polymorphisms in the DC-SIGNR neck domain on the interaction with pathogens. Virology 347: 354–363PubMedCrossRefGoogle Scholar
  102. 102.
    Gordon S (2002) Pattern recognition receptors: doubling up for the innate immune response. Cell 111: 927–930PubMedCrossRefGoogle Scholar
  103. 103.
    Nguyen DG, Hildreth JE (2003) Involvement of macrophage mannose receptor in the binding and transmission of HIV by macrophages. Eur J Immunol 33: 483–493PubMedCrossRefGoogle Scholar
  104. 104.
    Valladeau J, Duvert-Frances V, Pin JJ, Dezutter-Dambuyant C, Vincent C, Massacrier C, Vincent J, Yoneda K, Banchereau J, Caux C et al. (1999) The monoclonal antibody DCGM4 recognizes Langerin, a protein specific of Langerhans cells, and is rapidly internalized from the cell surface. Eur J Immunol 29: 2695–2704PubMedCrossRefGoogle Scholar
  105. 105.
    Stambach NS, Taylor ME (2003) Characterization of carbohydrate recognition by langerin, a C-type lectin of Langerhans cells. Glycobiology 13: 401–410PubMedCrossRefGoogle Scholar
  106. 106.
    McDermott R, Bausinger H, Fricker D, Spehner D, Proamer F, Lipsker D, Cazenave JP, Goud B, De La Salle H, Salamero J et al. (2004) Reproduction of Langerin/CD207 traffic and Birbeck granule formation in a human cell line model. J Invest Dermatol 123: 72–77PubMedCrossRefGoogle Scholar
  107. 107.
    Valladeau J, Ravel O, Dezutter-Dambuyant C, Moore K, Kleijmeer M, Liu Y, Duvert-Frances V, Vincent C, Schmitt D, Davoust J et al. (2000) Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules. Immunity 12: 71–81PubMedCrossRefGoogle Scholar
  108. 108.
    Tschachler E, Groh V, Popovic M, Mann DL, Konrad K, Safai B, Eron L, diMarzo Veronese F, Wolff K, Stingl G (1987) Epidermal Langerhans cells — a target for HTLV-III/LAV infection. J Invest Dermatol 88: 233–237PubMedCrossRefGoogle Scholar
  109. 109.
    Rappersberger K, Gartner S, Schenk P, Stingl G, Groh V, Tschachler E, Mann DL, Wolff K, Konrad K, Popovic M (1988) Langerhans’ cells are an actual site of HIV-1 replication. Intervirology 29: 185–194PubMedGoogle Scholar
  110. 110.
    Nair MP, Reynolds JL, Mahajan SD, Schwartz SA, Aalinkeel R, Bindukumar B, Sykes D (2005) RNAi-directed inhibition of DC-SIGN by dendritic cells: prospects for HIV-1 therapy. AAPS J 7: E572–578PubMedCrossRefGoogle Scholar
  111. 111.
    Woltman AM, Schlagwein N, van der Kooij SW, van Kooten C (2004) The novel cyclophilinbinding drug sanglifehrin A specifically affects antigen uptake receptor expression and endocytic capacity of human dendritic cells. J Immunol 172: 6482–6489PubMedGoogle Scholar
  112. 112.
    Tabarani G, Reina JJ, Ebel C, Vives C, Lortat-Jacob H, Rojo J, Fieschi F (2006) Mannose hyperbranched dendritic polymers interact with clustered organization of DC-SIGN and inhibit gp120 binding. FEBS Lett 580: 2402–2408PubMedCrossRefGoogle Scholar
  113. 113.
    Lasala F, Arce E, Otero JR, Rojo J, Delgado R (2003) Mannosyl glycodendritic structure inhibits DC-SIGN-mediated Ebola virus infection in cis and in trans. Antimicrob Agents Chemother 47: 3970–3972PubMedCrossRefGoogle Scholar
  114. 114.
    Simmons G, Reeves JD, Grogan CC, Vandenberghe LH, Baribaud F, Whitbeck JC, Burke E, Buchmeier MJ, Soilleux EJ, Riley JL et al. (2003) DC-SIGN and DC-SIGNR bind ebola glycoproteins and enhance infection of macrophages and endothelial cells. Virology 305: 115–123PubMedCrossRefGoogle Scholar
  115. 115.
    Alvarez CP, Lasala F, Carrillo J, Muniz O, Corbi AL, Delgado R (2002) C-type lectins DC-SIGN and L-SIGN mediate cellular entry by Ebola virus in cis and in trans. J Virol 76: 6841–6844PubMedCrossRefGoogle Scholar
  116. 116.
    Landers JJ, Cao Z, Lee I, Piehler LT, Myc PP, Myc A, Hamouda T, Galecki AT, Baker JR Jr (2002) Prevention of influenza pneumonitis by sialic acid-conjugated dendritic polymers. J Infect Dis 186: 1222–1230PubMedCrossRefGoogle Scholar
  117. 117.
    Groot F, Geijtenbeek TB, Sanders RW, Baldwin CE, Sanchez-Hernandez M, Floris R, van Kooyk Y, de Jong EC, Berkhout B (2005) Lactoferrin prevents dendritic cell-mediated human immunodeficiency virus type 1 transmission by blocking the DC-SIGN-gp120 interaction. J Virol 79: 3009–3015PubMedCrossRefGoogle Scholar
  118. 118.
    Naarding MA, Ludwig IS, Groot F, Berkhout B, Geijtenbeek TB, Pollakis G, Paxton WA (2005) Lewis X component in human milk binds DC-SIGN and inhibits HIV-1 transfer to CD4+ T lymphocytes. J Clin Invest 115: 3256–3264PubMedCrossRefGoogle Scholar
  119. 119.
    Jendrysik MA, Ghassemi M, Graham PJ, Boksa LA, Williamson PR, Novak RM (2005) Human cervicovaginal lavage fluid contains an inhibitor of HIV binding to dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin. J Infect Dis 192: 630–639PubMedCrossRefGoogle Scholar
  120. 120.
    Dakappagari N, Maruyama T, Renshaw M, Tacken P, Figdor C, Torensma R, Wild MA, Wu D, Bowdish K, Kretz-Rommel A (2006) Internalizing antibodies to the C-type lectins, L-SIGN and DC-SIGN, inhibit viral glycoprotein binding and deliver antigen to human dendritic cells for the induction of T cell responses. J Immunol 176: 426–440PubMedGoogle Scholar
  121. 121.
    Ji X, Gewurz H, Spear GT (2005) Mannose binding lectin (MBL) and HIV. Mol Immunol 42: 145–152PubMedCrossRefGoogle Scholar
  122. 122.
    Spear GT, Zariffard MR, Xin J, Saifuddin M (2003) Inhibition of DC-SIGN-mediated trans infection of T cells by mannose-binding lectin. Immunology 110: 80–85PubMedCrossRefGoogle Scholar
  123. 123.
    Ji X, Olinger GG, Aris S, Chen Y, Gewurz H, Spear GT (2005) Mannose-binding lectin binds to Ebola and Marburg envelope glycoproteins, resulting in blocking of virus interaction with DCSIGN and complement-mediated virus neutralization. J Gen Virol 86: 2535–2542PubMedCrossRefGoogle Scholar
  124. 124.
    Turville SG, Vermeire K, Balzarini J, Schols D (2005) Sugar-binding proteins potently inhibit dendritic cell human immunodeficiency virus type 1 (HIV-1) infection and dendritic-cell-directed HIV-1 transfer. J Virol 79: 13519–13527PubMedCrossRefGoogle Scholar
  125. 125.
    Barrientos LG, Gronenborn AM (2005) The highly specific carbohydrate-binding protein cyanovirin-N: structure, anti-HIV/Ebola activity and possibilities for therapy. Mini Rev Med Chem 5: 21–31PubMedGoogle Scholar
  126. 126.
    Tsai CC, Emau P, Jiang Y, Agy MB, Shattock RJ, Schmidt A, Morton WR, Gustafson KR, Boyd MR (2004) Cyanovirin-N inhibits AIDS virus infections in vaginal transmission models. AIDS Res Hum Retroviruses 20: 11–18PubMedCrossRefGoogle Scholar
  127. 127.
    Tsai CC, Emau P, Jiang Y, Tian B, Morton WR, Gustafson KR, Boyd MR (2003) Cyanovirin-N gel as a topical microbicide prevents rectal transmission of SHIV89.6P in macaques. AIDS Res Hum Retroviruses 19: 535–541PubMedCrossRefGoogle Scholar
  128. 128.
    Gieseler RK, Marquitan G, Hahn MJ, Perdon LA, Driessen WH, Sullivan SM, Scolaro MJ (2004) DC-SIGN-specific liposomal targeting and selective intracellular compound delivery to human myeloid dendritic cells: implications for HIV disease. Scand J Immunol 59: 415–424PubMedCrossRefGoogle Scholar
  129. 129.
    Korokhov N, de Gruijl TD, Aldrich WA, Triozzi PL, Banerjee PT, Gillies SD, Curiel TJ, Douglas JT, Scheper RJ, Curiel DT (2005) High efficiency transduction of dendritic cells by adenoviral vectors targeted to DC-SIGN. Cancer Biol Ther 4: 289–294PubMedCrossRefGoogle Scholar
  130. 130.
    Tacken PJ, de Vries IJ, Gijzen K, Joosten B, Wu D, Rother RP, Faas SJ, Punt CJ, Torensma R, Adema GJ et al. (2005) Effective induction of naive and recall T-cell responses by targeting antigen to human dendritic cells via a humanized anti-DC-SIGN antibody. Blood 106: 1278–1285PubMedCrossRefGoogle Scholar
  131. 131.
    Maguire CA, Sapinoro R, Girgis N, Rodriguez-Colon SM, Ramirez SH, Williams J, Dewhurst S (2006) Recombinant adenovirus type 5 vectors that target DC-SIGN, ChemR23 and alpha(v)beta3 integrin efficiently transduce human dendritic cells and enhance presentation of vectored antigens. Vaccine 24: 671–682PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag/Switzerland 2007

Authors and Affiliations

  • Stefan Pöhlmann
    • 1
  • Michel J. Tremblay
    • 2
    • 3
  1. 1.Institute for Clinical and Molecular Virology and Nikolaus-Fiebiger-Center for Molecular MedicineUniversity Erlangen-NürnbergErlangenGermany
  2. 2.Laboratory of Human Immuno-Retrovirology, Research Center in Infectious DiseasesCHUL Research CenterQuebecCanada
  3. 3.Faculty of MedicineLaval UniversityQuebecCanada

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