Cellular Entry of Retroviruses

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 790)

Abstract

The retrovirus family contains several important human and animal pathogens, including the human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS). Studies with retroviruses were instrumental to our present understanding of the cellular entry of enveloped viruses in general. For instance, studies with alpharetroviruses defined receptor engagement, as opposed to low pH, as a trigger for the envelope protein-driven membrane fusion. The insights into the retroviral entry process allowed the generation of a new class of antivirals, entry inhibitors, and these therapeutics are at present used for treatment of HIV/AIDS. In this chapter, we will summarize key concepts established for entry of avian sarcoma and leukosis virus (ASLV), a widely used model system for retroviral entry. We will then review how foamy virus and HIV, primate- and human retroviruses, enter target cells, and how the interaction of the viral and cellular factors involved in the cellular entry of these viruses impacts viral tropism, pathogenesis and approaches to therapy and vaccine development.

Keywords

Lymphoma Tyrosine Influenza Tuberculosis Sarcoma 

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References

  1. 1.
    Cohen MS, Hellmann N, Levy JA et al. The spread, treatment, and prevention of HIV-1: evolution of a global pandemic. J Clin Invest 2008; 118:1244–54.PubMedCrossRefGoogle Scholar
  2. 2.
    Karlsson GB, Halloran M, Schenten D et al. The envelope glycoprotein ectodomains determine the efficiency of CD4+ T lymphocyte depletion in simian-human immunodeficiency virus-infected macaques. J Exp Med 1998; 188:1159–71.PubMedCrossRefGoogle Scholar
  3. 3.
    Coffin JM, Hughes SH, Varmus HE. 1997. Retroviruses, vol. 843. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.Google Scholar
  4. 4.
    Goff SP. 2007. Retroviridae: The retroviruses and their replication, p. 1999–2070. In D. M. Knipe, Howley, P. M. (ed.), Fields Virology, vol. 2. Wolters Kuwer/Lippincott Williams & Wilkins, Philadelphia.Google Scholar
  5. 5.
    Goodier JL, Kazazian HH Jr. Retrotransposons revisited: the restraint and rehabilitation of parasites. Cell 2008; 135:23–35.PubMedCrossRefGoogle Scholar
  6. 6.
    Poiesz BJ, Ruscetti FW, Gazdar AF et al. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci USA 1980; 77:7415–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Barré-Sinoussi F, Chermann JC, Rey F et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 1983; 220:868–71.PubMedCrossRefGoogle Scholar
  8. 8.
    Einfeld D, Hunter E. Oligomeric structure of a prototype retrovirus glycoprotein. Proc Natl Acad Sci USA 1988; 85:8688–92.PubMedCrossRefGoogle Scholar
  9. 9.
    Hunter E, Hill E, Hardwick M et al. Complete sequence of the Rous sarcoma virus env gene: identification of structural and functional regions of its product. J Virol 1983; 46:920–36.PubMedGoogle Scholar
  10. 10.
    Purchio AF, Jovanovich S, Erikson RL. Sites of synthesis of viral proteins in avian sarcoma virus-infected chicken cells. J Virol 1980; 35:629–36.PubMedGoogle Scholar
  11. 11.
    Dong JY, Dubay JW, Perez LG et al. Mutations within the proteolytic cleavage site of the Rous sarcoma virus glycoprotein define a requirement for dibasic residues for intracellular cleavage. J Virol 1992; 66:865–74.PubMedGoogle Scholar
  12. 12.
    Leamnson RN, Halpern MS. Subunit structure of the glycoprotein complex of avian tumor virus. J Virol 1976; 18:956–68.PubMedGoogle Scholar
  13. 13.
    Perez LG, Hunter E. Mutations within the proteolytic cleavage site ofthe Rous sarcoma virus glycoprotein that block processing to gp85 and gp37. J Virol 1987; 61:1609–14.PubMedGoogle Scholar
  14. 14.
    Delos SE, Burdick MJ, White JM. A single glycosylation site within the receptor-binding domain of the avian sarcoma/leukosis virus glycoprotein is critical for receptor binding. Virology 2002; 294:354–63.PubMedCrossRefGoogle Scholar
  15. 15.
    Harrison SC. Viral membrane fusion. Nat Struct Mol Biol 2008; 15:690–8.PubMedCrossRefGoogle Scholar
  16. 16.
    White JM, Delos SE, Brecher M et al. Structures and mechanisms of viral membrane fusion proteins: multiple variations on a common theme. Crit Rev Biochem Mol Biol 2008; 43:189–219.PubMedCrossRefGoogle Scholar
  17. 17.
    Gallaher WR. Similar structural models of the transmembrane proteins of Ebola and avian sarcoma viruses. Cell 1996; 85:477–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Barnard RJ, Young JA. Alpharetrovirus envelope-receptor interactions. Curr Top Microbiol Immunol 2003; 281:107–36.PubMedCrossRefGoogle Scholar
  19. 19.
    Barnard RJ, Elleder D, Young JA. Avian sarcoma and leukosis virus-receptor interactions: from classical genetics to novel insights into virus-cell membrane fusion. Virology 2006; 344:25–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Bates P, Young JA, Varmus HE. A receptor for subgroup A Rous sarcoma virus is related to the low density lipoprotein receptor. Cell 1993; 74:1043–51.PubMedCrossRefGoogle Scholar
  21. 21.
    Young JA, Bates P, Varmus HE. Isolation of a chicken gene that confers susceptibility to infection by subgroup A avian leukosis and sarcoma viruses. J Virol 1993; 67:1811–6.PubMedGoogle Scholar
  22. 22.
    Rong L, Bates P. Analysis of the subgroup A avian sarcoma and leukosis virus receptor: the 40-residue, cysteine-rich, low-density lipoprotein receptor repeat motif of Tva is sufficient to mediate viral entry. J Virol 1995; 69:4847–53.PubMedGoogle Scholar
  23. 23.
    Zingler K, Belanger C, Peters R et al. Identification and characterization of the viral interaction determinant of the subgroup A avian leukosis virus receptor. J Virol 1995; 69:4261–6.PubMedGoogle Scholar
  24. 24.
    Brojatsch J, Naughton J, Rolls MM et al. CAR1, a TNFR-related protein, is a cellular receptor for cytopathic avian leukosis-sarcoma viruses and mediates apoptosis. Cell 1996; 87:845–55.PubMedCrossRefGoogle Scholar
  25. 25.
    Smith EJ, Brojatsch J, Naughton J et al. The CAR1 gene encoding a cellular receptor specific for subgroup B and D avian leukosis viruses maps to the chicken tvb locus. J Virol 1998; 72:3501–3.PubMedGoogle Scholar
  26. 26.
    Adkins HB, Brojatsch J, Naughton J et al. Identification of a cellular receptor for subgroup E avian leukosis virus. Proc Natl Acad Sci USA 1997; 94:11617–22.PubMedCrossRefGoogle Scholar
  27. 27.
    Bansal A, Shaw KL, Edwards BH et al. Characterization of the R572T point mutant of a putative cleavage site in human foamy virus Env. J Virol 2000; 74:2949–54.PubMedCrossRefGoogle Scholar
  28. 28.
    Knauss DJ, Young JA. A fifteen-amino-acid TVB peptide serves as a minimal soluble receptor for subgroup B avian leukosis and sarcoma viruses. J Virol 2002; 76:5404–10.PubMedCrossRefGoogle Scholar
  29. 29.
    Elleder D, Stepanets V, Melder DC et al. The receptor for the subgroup C avian sarcoma and leukosis viruses, Tvc, is related to mammalian butyrophilins, members of the immunoglobulin superfamily. J Virol 2005; 79:10408–19.PubMedCrossRefGoogle Scholar
  30. 30.
    Munguia A, Federspiel MJ. Efficient subgroup C avian sarcoma and leukosis virus receptor activity requires the IgV domain of the Tvc receptor and proper display on the cell membrane. J Virol 2008; 82:11419–28.PubMedCrossRefGoogle Scholar
  31. 31.
    Mothes W, Boerger AL, Narayan S et al. Retroviral entry mediated by receptor priming and low pH triggering of an envelope glycoprotein. Cell 2000; 103:679–89.PubMedCrossRefGoogle Scholar
  32. 32.
    Barnard RJ, Narayan S, Dornadula G et al. Low pH is required for avian sarcoma and leukosis virus Env-dependent viral penetration into the cytosol and not for viral uncoating. J Virol 2004; 78:10433–41.PubMedCrossRefGoogle Scholar
  33. 33.
    Earp LJ, Delos SE, Netter RC et al. The avian retrovirus avian sarcoma/leukosis virus subtype A reaches the lipid mixing stage of fusion at neutral pH. J Virol 2003; 77:3058–66.PubMedCrossRefGoogle Scholar
  34. 34.
    Melikyan GB, Barnard RJ, Abrahamyan LG, Mothes W, Young JA. Imaging individual retroviral fusion events: from hemifusion to pore formation and growth. Proc Natl Acad Sci USA 2005; 102:8728–33.PubMedCrossRefGoogle Scholar
  35. 35.
    Melikyan GB, Barnard RJ, Markosyan RM, Young JA, Cohen FS. Low pH is required for avian sarcoma and leukosis virus Env-induced hemifusion and fusion pore formation but not for pore growth. J Virol 2004; 78:3753–62.PubMedCrossRefGoogle Scholar
  36. 36.
    Cóte M, Zheng YM, Liu SL. Receptor binding and low pH coactivate oncogenic retrovirus envelope-mediated fusion. J Virol 2009; 83:11447–55.PubMedCrossRefGoogle Scholar
  37. 37.
    Fauquet C, Mayo M, Maniloff J et al, eds. 2005. Virus Taxonomy: Eighth Report of the International Committee on Taxonomy of Viruses. Academic Press, San Diego.Google Scholar
  38. 38.
    Lindemann D, Goepfert PA. The foamy virus envelope glycoproteins. Curr Top Microbiol Immunol 2003; 277:111–29.PubMedCrossRefGoogle Scholar
  39. 39.
    Geiselhart V, Schwantes A, Bastone P et al. Features of the Env leader protein and the N-terminal Gag domain of feline foamy virus important for virus morphogenesis. Virology 2003; 310:235–44.PubMedCrossRefGoogle Scholar
  40. 40.
    Lindemann D, Pietschmann T, Picard-Maureau M et al. A particle-associated glycoprotein signal peptide essential for virus maturation and infectivity. J Virol 2001; 75:5762–71.PubMedCrossRefGoogle Scholar
  41. 41.
    Wilk T, Geiselhart V, Frech M et al. Specific interaction of a novel foamy virus env leader protein with the n-terminal gag domain. J Virol 2001; 75:7995–8007.PubMedCrossRefGoogle Scholar
  42. 42.
    Duda A, Stange A, Luftenegger D et al. Prototype foamy virus envelope glycoprotein leader peptide processing is mediated by a furin-like cellular protease, but cleavage is not essential for viral infectivity. J Virol 2004; 78:13865–70.PubMedCrossRefGoogle Scholar
  43. 43.
    Geiselhart V, Bastone P, Kempf T et al. Furin-mediated cleavage of the feline foamy virus Env leader protein. J Virol 2004; 78:13573–81.PubMedCrossRefGoogle Scholar
  44. 44.
    Pietschmann T, Zentgraf H, Rethwilm A et al. An evolutionarily conserved positively charged amino acid in the putative membrane-spanning domain of the foamy virus envelope protein controls fusion activity. J Virol 2000; 74:4474–82.PubMedCrossRefGoogle Scholar
  45. 45.
    Wilk T, de Haas F, Wagner A et al. The intact retroviral Env glycoprotein of human foamy virus is a trimer. J Virol 2000; 74:2885–7.PubMedCrossRefGoogle Scholar
  46. 46.
    Baldwin DN, Linial ML. The roles of Pol and Env in the assembly pathway of human foamy virus. J Virol 1998; 72:3658–65.PubMedGoogle Scholar
  47. 47.
    Fischer N, Heinkelein M, Lindemann D et al. Foamy virus particle formation. J Virol 1998; 72:1610–5.PubMedGoogle Scholar
  48. 48.
    Shaw KL, Lindemann D, Mulligan MJ et al Foamy virus envelope glycoprotein is sufficient for particle budding and release. J Virol 2003; 77:2338–48.PubMedCrossRefGoogle Scholar
  49. 49.
    Stanke N, Stange A, Lüftenegger D et al. Ubiquitination of the Prototype Foamy Virus Envelope Glycoprotein Leader Peptide Regulates Subviral Particle Release. J Virol 2005; 79:15074–83.PubMedCrossRefGoogle Scholar
  50. 50.
    Stange A, Luftenegger D, Reh J et al. Subviral particle release determinants of prototype foamy virus. J Virol 2008; 82:9858–69.PubMedCrossRefGoogle Scholar
  51. 51.
    Lüftenegger D, Picard-Maureau M, Stanke N et al. Analysis and function of prototype foamy virus envelope N glycosylation. J Virol 2005; 79:7664–72.PubMedCrossRefGoogle Scholar
  52. 52.
    Goepfert PA, Shaw KL, Ritter GD Jr. et al. A sorting motif localizes the foamy virus glycoprotein to the endoplasmic reticulum. J Virol 1997; 71:778–84.PubMedGoogle Scholar
  53. 53.
    Goepfert PA, Wang G, Mulligan MJ. Identification of an ER retrieval signal in a retroviral glycoprotein. Cell 1995; 82:543–4.PubMedCrossRefGoogle Scholar
  54. 54.
    Tobaly-Tapiero J, Bittoun P, Neves M et al. Isolation and characterization of an equine foamy virus. J Virol 2000; 74:4064–73.PubMedCrossRefGoogle Scholar
  55. 55.
    Yu SF, Eastman SW, Linial ML. Foamy virus capsid assembly occurs at a pericentriolar region through a cytoplasmic targeting/retention signal in Gag. Traffic 2006; 7:966–77PubMedCrossRefGoogle Scholar
  56. 56.
    Hill CL, Bieniasz PD, McClure MO. Properties of human foamy virus relevant to its development as a vector for gene therapy. J Gen Virol 1999; 80:2003–9.PubMedGoogle Scholar
  57. 57.
    Stirnnagel K, Luftenegger D, Stange A et al. Analysis of prototype foamy virus particle-host cell interaction with autofluorescent retroviral particles. Retrovirology 2010; 7:45.PubMedCrossRefGoogle Scholar
  58. 58.
    Berg A, Pietschmann T, Rethwilm A, Lindemann D. Determinants of foamy virus envelope glycoprotein mediated resistance to superinfection. Virology 2003; 314:243–52.PubMedCrossRefGoogle Scholar
  59. 59.
    Duda A, Luftenegger D, Pietschmann T et al. Characterization of the prototype foamy virus envelope glycoprotein receptor-binding domain. J Virol 2006; 80:8158–67.PubMedCrossRefGoogle Scholar
  60. 60.
    Picard-Maureau M, Jarmy G, Berg A et al. Foamy Virus Envelope Glycoprotein-Mediated Entry Involves a pH-Dependent Fusion Process. J Virol 2003; 77:4722–30.PubMedCrossRefGoogle Scholar
  61. 61.
    Petit C, Giron ML, Tobaly-Tapiero J et al. Targeting of incoming retroviral Gag to the centrosome involves a direct interaction with the dynein light chain 8. J Cell Sci 2003; 116:3433–42.PubMedCrossRefGoogle Scholar
  62. 62.
    Saib A, Puvion Dutilleul F, Schmid M et al. Nuclear targeting of incoming human foamy virus Gag proteins involves a centriolar step. J Virol 1997; 71:1155–61.PubMedGoogle Scholar
  63. 63.
    Lehmann-Che J, Renault N, Giron ML et al. Centrosomal latency of incoming foamy viruses in resting cells. PLoS Pathog 2007; 3:e74.PubMedCrossRefGoogle Scholar
  64. 64.
    Matthes D, Wiktorowicz T, Zahn J et al. Basic residues in the foamy virus Gag protein. J Virol 2011; 85:3986–95.PubMedCrossRefGoogle Scholar
  65. 65.
    Zhadina M, McClure MO, Johnson MC et al. Ubiquitin-dependent virus particle budding without viral protein ubiquitination. Proc Natl Acad Sci USA 2007; 104:20031–6.PubMedCrossRefGoogle Scholar
  66. 66.
    Eastman SW, Linial ML. Identification of a conserved residue of foamy virus Gag required for intracellular capsid assembly. J Virol 2001; 75:6857–64.PubMedCrossRefGoogle Scholar
  67. 67.
    Linial ML, Eastman SW. Particle assembly and genome packaging. Curr Top Microbiol Immunol 2003; 277:89–110.PubMedCrossRefGoogle Scholar
  68. 68.
    Pfrepper KI, Löchelt M, Schnolzer M et al. Expression and molecular characterization of an enzymatically active recombinant human spumaretrovirus protease. Biochem Biophys Res Commun 1997; 237:548–53.PubMedCrossRefGoogle Scholar
  69. 69.
    Zemba M, Wilk T, Rutten T et al. The carboxy-terminal p3Gag domain of the human foamy virus Gag precursor is required for efficient virus infectivity. Virology 1998; 247:7–13.PubMedCrossRefGoogle Scholar
  70. 70.
    Cartellieri M, Rudolph W, Herchenröder O et al. Determination of the relative amounts of Gag and Pol proteins in foamy virus particles. Retrovirology 2005; 2:44.PubMedCrossRefGoogle Scholar
  71. 71.
    Enssle J, Fischer N, Moebes A et al. Carboxy-terminal cleavage of the human foamy virus Gag precursor molecule is an essential step in the viral life cycle. J Virol 1997; 71:7312–7.PubMedGoogle Scholar
  72. 72.
    Pfrepper KI, Löchelt M, Rackwitz HR et al. Molecular characterization of proteolytic processing of the Gag proteins of human spumavirus. J Virol 1999; 73:7907–11.PubMedGoogle Scholar
  73. 73.
    Lehmann-Che J, Giron ML, Delelis O et al. Protease-dependent uncoating of a complex retrovirus. J Virol 2005; 79:9244–53.PubMedCrossRefGoogle Scholar
  74. 74.
    Keele BF, Van Heuverswyn F, Li Y et al. Chimpanzee reservoirs of pandemic and nonpandemic HIV-1. Science 2006; 313:523–6.PubMedCrossRefGoogle Scholar
  75. 75.
    Van Heuverswyn F, Li Y, Neel C et al. Human immunodeficiency viruses: SIV infection in wild gorillas. Nature 2006; 444:164.PubMedCrossRefGoogle Scholar
  76. 76.
    Gao F, Bailes E, Robertson DL et al. Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes. Nature 1999; 397:436–41.PubMedCrossRefGoogle Scholar
  77. 77.
    Hahn BH, Shaw GM, De Cock KM et al. AIDS as a zoonosis: scientific and public health implications. Science 2000; 287:607–14.PubMedCrossRefGoogle Scholar
  78. 78.
    Plantier JC, Leoz M, Dickerson JE et al. A new human immunodeficiency virus derived from gorillas. Nat Med 2009; 15:871–2.PubMedCrossRefGoogle Scholar
  79. 79.
    de Silva TI, Cotten M, Rowland-Jones SL. HIV-2: the forgotten AIDS virus. Trends Microbiol 2008; 16:588–95.PubMedCrossRefGoogle Scholar
  80. 80.
    Gao F, Yue L, White AT et al. Human infection by genetically diverse SIVSM-related HIV-2 in west Africa. Nature 1992; 358:495–9.PubMedCrossRefGoogle Scholar
  81. 81.
    Hirsch VM, Olmsted RA, Murphey-Corb M et al. An African primate lentivirus (SIVsm) closely related to HIV-2. Nature 1989; 339:389–92.PubMedCrossRefGoogle Scholar
  82. 82.
    Levy JA. HIV pathogenesis: 25 years of progress and persistent challenges. AIDS 2009; 23:147–60.PubMedCrossRefGoogle Scholar
  83. 83.
    Douek DC, Roederer M, Koup RA. Emerging concepts in the immunopathogenesis of AIDS. Annu Rev Med 2009; 60:471–84.PubMedCrossRefGoogle Scholar
  84. 84.
    Schindler M, Munch J, Kutsch O et al. Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1. Cell 2006; 125:1055–67.PubMedCrossRefGoogle Scholar
  85. 85.
    Richman DD, Margolis DM, Delaney M et al. The challenge of finding a cure for HIV infection. Science 2009; 323:1304–7.PubMedCrossRefGoogle Scholar
  86. 86.
    Trono D, Van Lint C, Rouzioux C et al. HIV persistence and the prospect of long-term drug-free remissions for HIV-infected individuals. Science 2010; 329:174–80.PubMedCrossRefGoogle Scholar
  87. 87.
    Otteken A, Moss B. Calreticulin interacts with newly synthesized human immunodeficiency virus type 1 envelope glycoprotein, suggesting a chaperone function similar to that of calnexin. J Biol Chem 1996; 271:97–103.PubMedCrossRefGoogle Scholar
  88. 88.
    Otteken A, Earl PL, Moss B. Folding, assembly, and intracellular trafficking of the human immunodeficiency virus type 1 envelope glycoprotein analyzed with monoclonal antibodies recognizing maturational intermediates. J Virol 1996; 70:3407–15.PubMedGoogle Scholar
  89. 89.
    Li Y, Bergeron JJ, Luo L, Ou WJ et al. Effects of inefficient cleavage of the signal sequence of HIV-1 gp120 on its association with calnexin, folding, and intracellular transport. Proc Natl Acad Sci USA 1996; 93:9606–11.PubMedCrossRefGoogle Scholar
  90. 90.
    Li Y, Luo L, Thomas DY, Kang CY. The HIV-1 Env protein signal sequence retards its cleavage and down-regulates the glycoprotein folding. Virology 2000; 272:417–28.PubMedCrossRefGoogle Scholar
  91. 91.
    Scanlan CN, Offer J, Zitzmann N, Dwek RA. Exploiting the defensive sugars of HIV-1 for drug and vaccine design. Nature 2007; 446:1038–45.PubMedCrossRefGoogle Scholar
  92. 92.
    Li Y, Luo L, Rasool N, Kang CY. Glycosylation is necessary for the correctfolding of human immunodeficiency virus gp120 in CD4 binding. J Virol 1993; 67:584–8.PubMedGoogle Scholar
  93. 93.
    Bernstein HB, Tucker SP, Hunter E et al. Human immunodeficiency virus type 1 envelope glycoprotein is modified by O-linked oligosaccharides. J Virol 1994; 68:463–8.PubMedGoogle Scholar
  94. 94.
    Lu M, Blacklow SC, Kim PS. A trimeric structural domain of the HIV-1 transmembrane glycoprotein. Nat Struct Biol 1995; 2:1075–82.PubMedCrossRefGoogle Scholar
  95. 95.
    Thomas DJ, Wall JS, Hainfeld JF et al. gp160, the envelope glycoprotein of human immunodeficiency virus type 1, is a dimer of 125-kilodalton subunits stabilized through interactions between their gp41 domains. J Virol 1991; 65:3797–803.PubMedGoogle Scholar
  96. 96.
    Sanders RW, Venturi M, Schiffner L et al. The mannose-dependent epitope for neutralizing antibody 2G12 on human immunodeficiency virus type 1 glycoprotein gp120. J Virol 2002; 76:7293–305.PubMedCrossRefGoogle Scholar
  97. 97.
    Trkola A, Purtscher M, Muster T et al. Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1. J Virol 1996; 70:1100–8.PubMedGoogle Scholar
  98. 98.
    Hallenberger S, Bosch V, Angliker H, Shaw E, Klenk HD, Garten W. Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160. Nature 1992; 360:358–61.PubMedCrossRefGoogle Scholar
  99. 99.
    Miranda L, Wolf J, Pichuantes S, Duke R et al. Isolation of the human PC6 gene encoding the putative host protease for HIV-1 gp160 processing in CD4+ Tlymphocytes. Proc Natl Acad Sci USA 1996; 93:7695–700.PubMedCrossRefGoogle Scholar
  100. 100.
    McCune JM, Rabin LB, Feinberg MB et al. Endoproteolytic cleavage of gp160 is required forthe activation of human immunodeficiency virus. Cell 1988; 53:55–67.PubMedCrossRefGoogle Scholar
  101. 101.
    Liu J, Bartesaghi A, Borgnia MJ et al. Molecular architecture of native HIV-1 gp120 trimers. Nature 2008; 455:109–13.PubMedCrossRefGoogle Scholar
  102. 102.
    Zanetti G, Briggs JA, Grunewald K et al. Cryo-electron tomographic structure of an immunodeficiency virus envelope complex in situ. PLoS Pathog 2006; 2:e83.PubMedCrossRefGoogle Scholar
  103. 103.
    Zhu P, Liu J, Bess J Jr. et al. Distribution and three-dimensional structure of AIDS virus envelope spikes. Nature 2006; 441:847–52.PubMedCrossRefGoogle Scholar
  104. 104.
    Ganser-Pornillos BK, Yeager M, Sundquist WI. The structural biology of HIV assembly. Curr Opin Struct Biol 2008; 18:203–17.PubMedCrossRefGoogle Scholar
  105. 105.
    Sundquist WI, Hill CP. How to assemble a capsid. Cell 2007; 131:17–9.PubMedCrossRefGoogle Scholar
  106. 106.
    Bauby H, Lopez-Verges S, Hoeffel G et al. TIP47 is required for the production of infectious HIV-1 particles from primary macrophages. Traffic 2010; 11:455–67.PubMedCrossRefGoogle Scholar
  107. 107.
    Lopez-Verges S, Camus G, Blot G et al. Tail-interacting protein TIP47 is a connector between Gag and Env and is required for Env incorporation into HIV-1 virions. Proc Natl Acad Sci USA 2006; 103:14947–52.PubMedCrossRefGoogle Scholar
  108. 108.
    Cantin R, Methot S, Tremblay MJ. Plunder and stowaways: incorporation of cellular proteins by enveloped viruses. J Virol 2005; 79:6577–87.PubMedCrossRefGoogle Scholar
  109. 109.
    Ott DE. Cellular proteins in HIV virions. Rev Med Virol 1997; 7:167–80.PubMedCrossRefGoogle Scholar
  110. 110.
    Steffen I, Pöhlmann S. Peptide-based inhibitors of the HIV envelope protein and other class I viral fusion proteins. Curr Pharm Des 2010; 16:1143–58.PubMedCrossRefGoogle Scholar
  111. 111.
    Tilton JC, Doms RW. Entry inhibitors in the treatment of HIV-1 infection. Antiviral Res 2010; 85:91–100.PubMedCrossRefGoogle Scholar
  112. 112.
    Kwong PD, Wyatt R, Robinson J et al. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 1998; 393:648–59.PubMedCrossRefGoogle Scholar
  113. 113.
    Wyatt R, Kwong PD, Desjardins E et al. The antigenic structure of the HIV gp120 envelope glycoprotein. Nature 1998; 393:705–11.PubMedCrossRefGoogle Scholar
  114. 114.
    Rizzuto CD, Wyatt R, Hernandez-Ramos N et al. A conserved HIV gp120 glycoprotein structure involved in chemokine receptor binding. Science 1998; 280:1949–53.PubMedCrossRefGoogle Scholar
  115. 115.
    Wyatt R, Sodroski J. The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. Science 1998; 280:1884–8.PubMedCrossRefGoogle Scholar
  116. 116.
    Karlsson Hedestam GB, Fouchier RA, Phogat S et al. The challenges of eliciting neutralizing antibodies to HIV-1 and to influenza virus. Nat Rev Microbiol 2008; 6:143–55.PubMedCrossRefGoogle Scholar
  117. 117.
    Ugolini S, Mondor I, Sattentau QJ. HIV-1 attachment: another look. Trends Microbiol 1999; 7:144–9.PubMedCrossRefGoogle Scholar
  118. 118.
    Fortin JF, Cantin R, Lamontagne G et al. Host-derived ICAM-1 glycoproteins incorporated on human immunodeficiency virus type 1 are biologically active and enhance viral infectivity. J Virol 1997; 71:3588–96.PubMedGoogle Scholar
  119. 119.
    Münch J, Rucker E, Standker L et al. Semen-derived amyloid fibrils drastically enhance HIV infection. Cell 2007; 131:1059–71.PubMedCrossRefGoogle Scholar
  120. 120.
    Kim KA, Yolamanova M, Zirafi O et al. Semen-mediated enhancement of HIV infection is donor-dependent and correlates with the levels of SEVI. Retrovirology 2010; 7:55.PubMedCrossRefGoogle Scholar
  121. 121.
    Cameron PU, Freudenthal PS, Barker JM et al. Dendritic cells exposed to human immunodeficiency virus type-1 transmit a vigorous cytopathic infection to CD4+ T cells. Science 1992; 257:383–7.PubMedCrossRefGoogle Scholar
  122. 122.
    Tsegaye TS, Pöhlmann S. The multiple facets of HIV attachment to dendritic cell lectins. Cell Microbiol 2010; 12:1553–61.PubMedCrossRefGoogle Scholar
  123. 123.
    Wu L, KewalRamani VN. Dendritic-cell interactions with HIV: infection and viral dissemination. Nat Rev Immunol 2006; 6:859–68.PubMedCrossRefGoogle Scholar
  124. 124.
    Curtis BM, Scharnowske S, Watson AJ. 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 1992; 89:8356–60.PubMedCrossRefGoogle Scholar
  125. 125.
    Feinberg H, Mitchell DA, Drickamer K et al. Structural basis for selective recognition of oligosaccharides by DC-SIGN and DC-SIGNR. Science 2001; 294:2163–6.PubMedCrossRefGoogle Scholar
  126. 126.
    Geijtenbeek TB, Kwon DS, Torensma R et al. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell 2000; 100:587–97.PubMedCrossRefGoogle Scholar
  127. 127.
    Geijtenbeek TB, Torensma R, van Vliet SJ et al. Identification of DC-SIGN, anovel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. Cell 2000; 100:575–85.PubMedCrossRefGoogle Scholar
  128. 128.
    Guo Y, Feinberg H, Conroy E et al. Structural basis for distinct ligand-binding and targeting properties of the receptors DC-SIGN and DC-SIGNR. Nat Struct Mol Biol 2004; 11:591–8.PubMedCrossRefGoogle Scholar
  129. 129.
    Lin G, Simmons G, Pöhlmann S et al. Differential N-linked glycosylation of human immunodeficiency virus and Ebola virus envelope glycoproteins modulates interactions with DC-SIGN and DC-SIGNR. J Virol 2003; 77:1337–46.PubMedCrossRefGoogle Scholar
  130. 130.
    Kwon DS, Gregorio G, Bitton N et al. DC-SIGN-mediated internalization of HIV is required for trans-enhancement of T cell infection. Immunity 2002; 16:135–44.PubMedCrossRefGoogle Scholar
  131. 131.
    McDonald D, Wu L, Bohks SM et al. Recruitment of HIV and its receptors to dendritic cell-T cell junctions. Science 2003; 300:1295–7.PubMedCrossRefGoogle Scholar
  132. 132.
    Boggiano C, Manel N, Littman DR. Dendritic cell-mediated trans-enhancement of human immunodeficiency virus type 1 infectivity is independent of DC-SIGN. J Virol 2007; 81:2519–23.PubMedCrossRefGoogle Scholar
  133. 133.
    Moris A, Nobile C, Buseyne F et al. DC-SIGN promotes exogenous MHC-I-restricted HIV-1 antigen presentation. Blood 2004; 103:2648–54.PubMedCrossRefGoogle Scholar
  134. 134.
    Moris A, Pajot A, Blanchet F et al. Dendritic cells and HIV-specific CD4+ T cells: HIV antigen presentation, T-cell activation, and viral transfer. Blood 2006; 108:1643–51.PubMedCrossRefGoogle Scholar
  135. 135.
    Nobile C, Petit C, Moris A et al. Covert human immunodeficiency virus replication in dendritic cells and in DC-SIGN-expressing cells promotes long-term transmission to lymphocytes. J Virol 2005; 79:5386–99.PubMedCrossRefGoogle Scholar
  136. 136.
    Turville SG, Santos JJ, Frank I et al. Immunodeficiency virus uptake, turnover, and 2-phase transfer in human dendritic cells. Blood 2004; 103:2170–9.PubMedCrossRefGoogle Scholar
  137. 137.
    He B, Qiao X, Klasse PJ et al. HIV-1 envelope triggers polyclonal Ig class switch recombination through a CD40-independent mechanism involving BAFF and C-type lectin receptors. J Immunol 2006; 176:3931–41.PubMedGoogle Scholar
  138. 138.
    Rappocciolo G, Piazza P, Fuller CL et al. DC-SIGN on B lymphocytes is required for transmission of HIV-1 to T lymphocytes. PLoS Pathog 2006; 2:e70.PubMedCrossRefGoogle Scholar
  139. 139.
    Boukour S, Masse JM, Benit L et al. Lentivirus degradation and DC-SIGN expression by human platelets and megakaryocytes. J Thromb Haemost 2006; 4:426–35.PubMedCrossRefGoogle Scholar
  140. 140.
    Chaipan C, Soilleux EJ, Simpson P et al. DC-SIGN and CLEC-2 mediate human immunodeficiency virus type 1 capture by platelets. J Virol 2006; 80:8951–60.PubMedCrossRefGoogle Scholar
  141. 141.
    Martin MP, Lederman MM, Hutcheson HB et al. Association of DC-SIGN promoter polymorphism with increased risk for parenteral, but not mucosal, acquisition of human immunodeficiency virus type 1 infection. J Virol 2004; 78:14053–6.PubMedCrossRefGoogle Scholar
  142. 142.
    Gringhuis SI, den Dunnen J, Litjens M et al. Carbohydrate-specific signaling through the DC-SIGN signalosome tailors immunity to Mycobacterium tuberculosis, HIV-1 and Helicobacter pylori. Nat Immunol 2009; 10:1081–8.PubMedCrossRefGoogle Scholar
  143. 143.
    Gringhuis SI, den Dunnen J, Litjens M et al. C-type lectin DC-SIGN modulates Toll-like receptor signaling via Raf-1 kinase-dependent acetylation of transcription factor NF-kappaB. Immunity 2007; 26:605–16.PubMedCrossRefGoogle Scholar
  144. 144.
    Gringhuis SI, van der Vlist M, van den Berg LM et al. HIV-1 exploits innate signaling by TLR8 and DC-SIGN for productive infection of dendritic cells. Nat Immunol 2010; 11:419–26.PubMedCrossRefGoogle Scholar
  145. 145.
    de Witte L, Nabatov A, Pion M et al. Langerin is a natural barrier to HIV-1 transmission by Langerhans cells. Nat Med 2007; 13:367–71.PubMedCrossRefGoogle Scholar
  146. 146.
    Nguyen DG, Hildreth JE. Involvement of macrophage mannose receptor in the binding and transmission of HIV by macrophages. Eur J Immunol 2003; 33:483–93.PubMedCrossRefGoogle Scholar
  147. 147.
    Trujillo JR, Rogers R, Molina RM et al. Noninfectious entry of HIV-1 into peripheral and brain macrophages mediated by the mannose receptor. Proc Natl Acad Sci USA 2007; 104:5097–102.PubMedCrossRefGoogle Scholar
  148. 148.
    Turville SG, Cameron PU, Handley A et al. Diversity of receptors binding HIV on dendritic cell subsets. Nat Immunol 2002; 3:975–83.PubMedCrossRefGoogle Scholar
  149. 149.
    Saifuddin M, Hart ML, Gewurz H et al. Interaction of mannose-binding lectin with primary isolates of human immunodeficiency virus type 1. J Gen Virol 2000; 81:949–55.PubMedGoogle Scholar
  150. 150.
    Klatzmann D, Champagne E, Chamaret S et al. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature 1984; 312:767–8.PubMedCrossRefGoogle Scholar
  151. 151.
    Maddon PJ, Dalgleish AG, McDougal JS et al. The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell 1986; 47:333–48.PubMedCrossRefGoogle Scholar
  152. 152.
    Bour S, Geleziunas R, Wainberg MA. The human immunodeficiency virus type 1 (HIV-1) CD4 receptor and its central role in promotion of HIV-1 infection. Microbiol Rev 1995; 59:63–93.PubMedGoogle Scholar
  153. 153.
    Jameson BA, Rao PE, Kong LI et al. Location and chemical synthesis of a binding site for HIV-1 on the CD4 protein. Science 1988; 240:1335–9.PubMedCrossRefGoogle Scholar
  154. 154.
    Chen B, Vogan EM, Gong H et al. Determining the structure of an unliganded and fully glycosylated SIV gp120 envelope glycoprotein. Structure 2005; 13:197–211.PubMedCrossRefGoogle Scholar
  155. 155.
    Edinger AL, Mankowski JL, Doranz BJ et al. CD4-independent, CCR5-dependent infection of brain capillary endothelial cells by a neurovirulent simian immunodeficiency virus strain. Proc Natl Acad Sci USA 1997; 94:14742–7.PubMedCrossRefGoogle Scholar
  156. 156.
    Endres MJ, Clapham PR, Marsh M et al. CD4-independent infection by HIV-2 is mediated by fusin/CXCR4. Cell 1996; 87:745–56.PubMedCrossRefGoogle Scholar
  157. 157.
    Martin KA, Wyatt R, Farzan M et al. CD4-independent binding of SIV gp120 to rhesus CCR5. Science 1997; 278:1470–3.PubMedCrossRefGoogle Scholar
  158. 158.
    Reeves JD, Schulz TF. The CD4-independent tropism of human immunodeficiency virus type 2 involves several regions of the envelope protein and correlates with a reduced activation threshold for envelope-mediated fusion. J Virol 1997; 71:1453–65.PubMedGoogle Scholar
  159. 159.
    Dumonceaux J, Nisole S, Chanel C et al. 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 1998; 72:512–9.PubMedGoogle Scholar
  160. 160.
    Hoffman TL, LaBranche CC, Zhang W et al. Stable exposure of the coreceptor-binding site in a CD4-independent HIV-1 envelope protein. Proc Natl Acad Sci USA 1999; 96:6359–64.PubMedCrossRefGoogle Scholar
  161. 161.
    Kolchinsky P, Mirzabekov T, Farzan M et al. Adaptation of aCCR5-using, primary human immunodeficiency virus type 1 isolate for CD4-independent replication. J Virol 1999; 73:8120–6.PubMedGoogle Scholar
  162. 162.
    Taylor BM, Foulke JS, Flinko R et al. An alteration of human immunodeficiency virus gp41 leads to reduced CCR5 dependence and CD4 independence. J Virol 2008; 82:5460–71.PubMedCrossRefGoogle Scholar
  163. 163.
    Edwards TG, Hoffman TL, Baribaud F et al. Relationships between CD4 independence, neutralization sensitivity, and exposure of a CD4-induced epitope in a human immunodeficiency virus type 1 envelope protein. J Virol 2001; 75:5230–9.PubMedCrossRefGoogle Scholar
  164. 164.
    Kolchinsky P, Kiprilov E, Sodroski J. Increased neutralization sensitivity of CD4-independent human immunodeficiency virus variants. J Virol 2001; 75:2041–50.PubMedCrossRefGoogle Scholar
  165. 165.
    Lusso P. HIV and the chemokine system: 10 years later. EMBO J 2006; 25:447–56.PubMedCrossRefGoogle Scholar
  166. 166.
    Huang CC, Tang M, Zhang MY et al. Structure of a V3-containing HIV-1 gp120 core. Science 2005; 310:1025–8.PubMedCrossRefGoogle Scholar
  167. 167.
    Farzan M, Mirzabekov T, Kolchinsky P et al. Tyrosine sulfation of the amino terminus of CCR5 facilitates HIV-1 entry. Cell 1999; 96:667–76.PubMedCrossRefGoogle Scholar
  168. 168.
    Huang CC, Lam SN, Acharya P et al. Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4. Science 2007; 317:1930–4.PubMedCrossRefGoogle Scholar
  169. 169.
    Sharon M, Kessler N, Levy R et al. Alternative conformations of HIV-1 V3 loops mimic beta hairpins in chemokines, suggesting a mechanism for coreceptor selectivity. Structure 2003; 11:225–36.PubMedCrossRefGoogle Scholar
  170. 170.
    Cormier EG, Dragic T. The crown and stem of the V3 loop play distinct roles in human immunodeficiency virus type 1 envelope glycoprotein interactions with the CCR5 coreceptor. J Virol 2002; 76:8953–7.PubMedCrossRefGoogle Scholar
  171. 171.
    Connor RI, Sheridan KE, Ceradini D et al. Change in coreceptor use correlates with disease progression in HIV-1-infected individuals. J Exp Med 1997; 185:621–8.PubMedCrossRefGoogle Scholar
  172. 172.
    Philpott S, Burger H, Charbonneau T et al. CCR5 genotype and resistance to vertical transmission of HIV-1. J Acquir Immune Defic Syndr 1999; 21:189–93.PubMedCrossRefGoogle Scholar
  173. 173.
    van’t Wout AB, Kootstra NA, Mulder-Kampinga GA et al. Macrophage-tropic variants initiate human immunodeficiency virus type 1 infection after sexual, parenteral, and vertical transmission. J Clin Invest 1994; 94:2060–7.CrossRefGoogle Scholar
  174. 174.
    Zhu T, Mo H, Wang N et al. Genotypic and phenotypic characterization of HIV-1 patients with primary infection. Science 1993; 261:1179–81.PubMedCrossRefGoogle Scholar
  175. 175.
    Margolis L, Shattock R. Selective transmission of CCR5-utilizing HIV-1: the ‘gatekeeper’ problem resolved? Nat Rev Microbiol 2006; 4:312–7.PubMedCrossRefGoogle Scholar
  176. 176.
    Dean M, Carrington M, Winkler C et al. 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 1996; 273:1856–62.PubMedCrossRefGoogle Scholar
  177. 177.
    Garred P, Eugen-Olsen J, Iversen AK et al. Dual effect of CCR5 delta 32 gene deletion in HIV-1-infected patients. Copenhagen AIDS Study Group. Lancet 1997; 349:1884.PubMedCrossRefGoogle Scholar
  178. 178.
    Huang Y, Paxton WA, Wolinsky SM et al. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med 1996; 2:1240–3.PubMedCrossRefGoogle Scholar
  179. 179.
    Michael NL, Chang G, Louie LG et al. The role of viral phenotype and CCR-5 gene defects in HIV-1 transmission and disease progression. Nat Med 1997; 3:338–40.PubMedCrossRefGoogle Scholar
  180. 180.
    Samson M, Libert F, Doranz BJ et al. Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 1996; 382:722–5.PubMedCrossRefGoogle Scholar
  181. 181.
    Hütter G, Nowak D, Mossner M et al. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med 2009; 360:692–8.PubMedCrossRefGoogle Scholar
  182. 182.
    Hütter G, Thiel E. Allogeneic transplantation of CCR5-deficient progenitor cells in a patient with HIV infection: an update after 3 years and the search for patient no. 2. AIDS 2011; 25:273–4.PubMedCrossRefGoogle Scholar
  183. 183.
    Huffnagle GB, McNeil LK, McDonald RA et al. Cutting edge: Role of C-C chemokine receptor 5 in organ-specific and innate immunity to Cryptococcus neoformans. J Immunol 1999; 163:4642–6.PubMedGoogle Scholar
  184. 184.
    Regoes RR, Bonhoeffer S. The HIV coreceptor switch: a population dynamical perspective. Trends Microbiol 2005; 13:269–77.PubMedCrossRefGoogle Scholar
  185. 185.
    Grivel JC, Margolis LB. CCR5-and CXCR4-tropic HIV-1 are equally cytopathic for their T-cell targets in human lymphoid tissue. Nat Med 1999; 5:344–6.PubMedCrossRefGoogle Scholar
  186. 186.
    Penn ML, Grivel JC, Schramm B et al. CXCR4 utilization is sufficient to trigger CD4+ T cell depletion in HIV-1-infected human lymphoid tissue. Proc Natl Acad Sci USA 1999; 96:663–8.PubMedCrossRefGoogle Scholar
  187. 187.
    Bleul CC, Wu L, Hoxie JA et al. The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes. Proc Natl Acad Sci USA 1997; 94:1925–30.CrossRefPubMedGoogle Scholar
  188. 188.
    Lee B, Sharron M, Montaner LJ et al. Quantification of CD4, CCR5, and CXCR4 levels on lymphocyte subsets, dendritic cells, and differentially conditioned monocyte-derived macrophages. Proc Natl Acad Sci USA 1999; 96:5215–20.PubMedCrossRefGoogle Scholar
  189. 189.
    Nagasawa T, Hirota S, Tachibana K et al. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 1996; 382:635–8.PubMedCrossRefGoogle Scholar
  190. 190.
    Zou YR, Kottmann AH, Kuroda M et al. Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature 1998; 393:595–9.PubMedCrossRefGoogle Scholar
  191. 191.
    Hendrix CW, Collier AC, Lederman MM et al. Safety, pharmacokinetics, and antiviral activity of AMD3100, aselective CXCR4 receptor inhibitor, in HIV-1 infection. J Acquir Immune Defic Syndr 2004; 37:1253–62.PubMedCrossRefGoogle Scholar
  192. 192.
    Calado M, Matoso P, Santos-Costa Q et al. Coreceptor usage by HIV-1 and HIV-2 primary isolates: the relevance of CCR8 chemokine receptor as an alternative coreceptor. Virology 2010; 408:174–82.PubMedCrossRefGoogle Scholar
  193. 193.
    Deng, HK, Unutmaz D, KewalRamani VN et al. Expression cloning of new receptors used by simian and human immunodeficiency viruses. Nature 1997; 388:296–300.PubMedCrossRefGoogle Scholar
  194. 194.
    Farzan M, Choe H, Martin K et al. Two orphan seven-transmembrane segment receptors which are expressed in CD4-positive cells support simian immunodeficiency virus infection. J Exp Med 1997; 186:405–11.PubMedCrossRefGoogle Scholar
  195. 195.
    Blaak H, Boers PH, Graters RA et al. CCR5, GPR15, and CXCR6 are major coreceptors of human immunodeficiency virus type 2 variants isolated from individuals with and without plasma viremia. J Virol 2005; 79:1686–700.PubMedCrossRefGoogle Scholar
  196. 196.
    Neil SJ, Aasa-Chapman MM, Clapham PR et al. The promiscuous CC chemokine receptor D6 is a functional coreceptor for primary isolates of human immunodeficiency virus type 1 (HIV-1) and HIV-2 on astrocytes. J Virol 2005; 79:9618–24.PubMedCrossRefGoogle Scholar
  197. 197.
    Pöhlmann S, Krambiegel M, Kirchhoff F. Coreceptor usage of BOB/GPR15 and Bonzo/STRL33 by primary isolates of human immunodeficiency virus type 1. J Gen Virol 1999; 80:1241–51.PubMedGoogle Scholar
  198. 198.
    Cilliers T, Willey S, Sullivan WM et al. Use of alternate coreceptors on primary cells by two HIV-1 isolates. Virology 2005; 339:136–44.PubMedCrossRefGoogle Scholar
  199. 199.
    Pöhlmann S, Stolte N, Munch J et al. Co-receptor usage of BOB/GPR15 in addition to CCR5 has no significant effect on replication of simian immunodeficiency virus in vivo. J Infect Dis 1999; 180:1494–502.PubMedCrossRefGoogle Scholar
  200. 200.
    Zhang Y, Lou B, Lal RB et al. Use of inhibitors to evaluate coreceptor usage by simian and simian/human immunodeficiency viruses and human immunodeficiency virus type 2 in primary cells. J Virol 2000; 74:6893–910.PubMedCrossRefGoogle Scholar
  201. 201.
    Zhang YJ, Dragic T, Cao Y et al. Use of coreceptors other than CCR5 by non-syncytium-inducing adult and pediatric isolates of human immunodeficiency virus type 1 is rare in vitro. J Virol 1998; 72:9337–44.PubMedGoogle Scholar
  202. 202.
    Zhang YJ, Moore JP. Will multiple coreceptors need to be targeted by inhibitors of human immunodeficiency virus type 1 entry? J Virol 1999; 73:3443–8.PubMedGoogle Scholar
  203. 203.
    Miyauchi K, Kim Y, Latinovic O et al. HIV enters cells via endocytosis and dynamin-dependent fusion with endosomes. Cell 2009; 137:433–44.PubMedCrossRefGoogle Scholar
  204. 204.
    Melikyan GB. Common principles and intermediates of viral protein-mediated fusion: the HIV-1 paradigm. Retrovirology 2008; 5:111.PubMedCrossRefGoogle Scholar
  205. 205.
    Conley AJ, Kessler JA 2nd, Boots LJ et al. Neutralization of divergent human immunodeficiency virus type 1 variants and primary isolates by IAM-41-2F5, an anti-gp41 human monoclonal antibody. Proc Natl Acad Sci USA 1994; 91:3348–52.PubMedCrossRefGoogle Scholar
  206. 206.
    Stiegler G, Kunert R, Purtscher M et al. A potent cross-clade neutralizing human monoclonal antibody against a novel epitope on gp41 of human immunodeficiency virus type 1. AIDS Res Hum Retroviruses 2001; 17:1757–65.PubMedCrossRefGoogle Scholar
  207. 207.
    Eckert DM, Kim PS. Mechanisms of viral membrane fusion and its inhibition. Annu Rev Biochem 2001; 70:777–810.PubMedCrossRefGoogle Scholar
  208. 208.
    Munch J, Standker L, Adermann K et al. Discovery and optimization of a natural HIV-1 entry inhibitor targeting the gp41 fusion peptide. Cell 2007; 129:263–75.PubMedCrossRefGoogle Scholar
  209. 209.
    Forssmann WG, The YH, Stoll M et al. Short-term monotherapy in HIV-infected patients with a virus entry inhibitor against the gp41 fusion peptide. Sci Transi Med 2010; 2:re63.Google Scholar
  210. 210.
    Furuta RA, Wild CT, Weng Y et al. Capture of an early fusion-active conformation of HIV-1 gp41. Nat Struct Biol 1998; 5:276–9.PubMedCrossRefGoogle Scholar
  211. 211.
    Gallo SA, Clore GM, Louis JM et al. Temperature-dependent intermediates in HIV-1 envelope glycoprotein-mediated fusion revealed by inhibitors that target N-and C-terminal helical regions of HIV-1 gp41. Biochemistry 2004; 43:8230–3.PubMedCrossRefGoogle Scholar
  212. 212.
    Kilgore NR, Salzwedel K, Reddick M et al. Direct evidence that C-peptide inhibitors of human immunodeficiency virus type 1 entry bind to the gp41 N-helical domain in receptor-activated viral envelope. J Virol 2003; 77:7669–72.PubMedCrossRefGoogle Scholar
  213. 213.
    Chan DC, Fass D, Berger JM et al. Core structure of gp41 from the HIV envelope glycoprotein. Cell 1997; 89:263–73.PubMedCrossRefGoogle Scholar
  214. 214.
    Melikyan GB, Markosyan RM, Hemmati H et al. Evidence that the transition of HIV-1 gp41 into a six-helix bundle, not the bundle configuration, induces membrane fusion. J Cell Biol 2000; 151:413–23.PubMedCrossRefGoogle Scholar
  215. 215.
    Weissenhorn W, Dessen A, Harrison SC et al. Atomic structure of the ectodomain from HIV-1 gp41. Nature 1997; 387:426–30.PubMedCrossRefGoogle Scholar
  216. 216.
    Markosyan RM, Cohen FS, Melikyan GB. HIV-1 envelope proteins complete their folding into six-helix bundles immediately after fusion pore formation. Mol Biol Cell 2003; 14:926–38.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2013

Authors and Affiliations

  • Dirk Lindemann
    • 1
  • Imke Steffen
    • 2
    • 3
  • Stefan Pöhlmann
    • 2
    • 4
  1. 1.Institute for Virology, Medical Faculty Carl Gustav CarusTechnische Universität DresdenDresdenGermany
  2. 2.Institute for VirologyHannover Medical SchoolHannoverGermany
  3. 3.Blood Systems Research InstituteSan FranciscoUSA
  4. 4.German Primate CenterGöttingenGermany

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