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Mechanism of HIV-1 Entry into CD4+ T Cells

  • Barry S. Stein
  • Edgar G. Engleman
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 300)

Abstract

One hallmark of enveloped RNA viruses is that they are inherently fusogenic with membranes of their respective target cells. This property plays an obligate role in viral entry and is triggered and catalyzed by specific virally encoded envelope glycoproteins (1). After receptor binding by such envelope components, entry of viral genomic information into the cytosol of susceptible target cells is known to occur by two distinct mechanisms: either by direct fusion of the virus envelope with the plasma membrane in a pH-independent fashion (2), or by rapid internalization of virus via receptor-mediated endocytosis into acidic vesicles where viral envelope glycoproteins undergo requisite low pH-dependent conformational changes that facilitate virus envelope fusion with endosomal membranes (3,4). Viral entry, per se, can be strictly defined as the delivery of genomic viral RNA into the cytoplasmic compartment of host cells consequent to membrane fusion. Therefore, the simple incorporation of a virion into an endocytic vesicle, in and by itself, does not constitute viral entry in the true sense, unless the virus envelope subsequently fuses with the endosomal membrane. Endocytosed virus particles which fail to undergo intravesicular membrane fusion are likely destined for lysosomal degradation.

Keywords

Human Immunodeficiency Virus Human Immunodeficiency Virus Type Membrane Fusion Envelope Glycoprotein Sendai Virus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    J. White, M. Kielian, and A. Helenius, Membrane fusion proteins of enveloped animal viruses, Quart. Rev. Biophys. 16:151 (1983).CrossRefGoogle Scholar
  2. 2.
    K. Apostolov and J. D. Almeida, Interaction of Sendai virus (HV) with human erythrocytes: a morphological study of hemolysis and cell fusion, J. Gen. Virol. 15:227 (1972).PubMedCrossRefGoogle Scholar
  3. 3.
    A. Helenius, J. Kartenbeck, K. Simons, and E. Fries, On entry of Semliki forest virus into BHK-21 cells, J. Cell Biol. 84:404 (1980).PubMedCrossRefGoogle Scholar
  4. 4.
    K. S. Matlin, H. Reggio, A. Helenius, and K. Simons, Infectious entry pathway of influenza virus in a canine kidney cell line, J. Cell Biol. 91:601 (1981).PubMedCrossRefGoogle Scholar
  5. 5.
    A. G. Da Gleish, P. C. L. Beverley, P. R. Clapham, D. H. Crawford, M. F. Greaves, and R. A. Weiss, The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus, Nature 312:763 (1984).CrossRefGoogle Scholar
  6. 6.
    D. Klatzmann, E. Champagne, S. Chamaret, J. Gruest, D. Guetard, T. Hercend, J.-C. Gluckman, and L. Montagnier, T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV, Nature 312:767 (1984).PubMedCrossRefGoogle Scholar
  7. 7.
    D. Klatzmann, F. Barre-Sinoussi, M. T. Nugeyre, C. Dauget, E. Vilmer, C. Griscelli, F. Brun-Vezinet, C. Rouzioux, J.-C. Chermann, and L. Montagnier, Selective tropism of lymphadenopathy associated virus (LAV) for helper-inducer T lymphocytes, Science 225:59 (1984).PubMedCrossRefGoogle Scholar
  8. 8.
    S. Gartner, P. Markovits, D. M. Markovitz, M. H. Kaplan, R. C. Gallo, and M. Popovic, The role of mononuclear phagocytes in HTLV-III/LAV infection, Science 233:215 (1986).PubMedCrossRefGoogle Scholar
  9. 9.
    D. D. Ho, T. R. Rota, and M. S. Hirsch, Infection of monocyte/macrophages by human T lymphotropic virus type III, J. Clin. Invest. 77:1712 (1986).PubMedCrossRefGoogle Scholar
  10. 10.
    J. K. A. Nicholson, G. D. Cross, C. S. Callaway, and J. S. McDougal, In vitro infection of human monocytes with human T lymphotropic virus type Ill/lymphadenopathy-associated virus (HTLV-III/LAV), J. Immunol. 137:323 (1986).PubMedGoogle Scholar
  11. 11.
    E. Tschachler, V. Groh, M. Popovic, D. L. Mann, K. Konrad, B. Safai, L. Eron, F. D. Veronese, K. Wolff, and G. Stingl, Epidermal Langerhans cells-a target for HTLV-III/LAV infection, J. Invest. Dermatol. 88:233 (1987).PubMedCrossRefGoogle Scholar
  12. 12.
    S. Patterson and S. C. Knight, Susceptibility of human peripheral blood dendritic cells to infection by human immunodeficiency virus, J. Gen. Virol. 68:1177 (1987).PubMedCrossRefGoogle Scholar
  13. 13.
    E. G. Engleman, C. Benike, C. Grumet, and R. L. Evans, Activation of human T lymphocyte subsets: helper and suppressor/cytotoxic T cells recognize and respond to distinct histocompatibility antigens, J. Immunol. 127:2124 (1981).PubMedGoogle Scholar
  14. 14.
    S. L. Swain, T cell subsets and the recognition of MHC class, Immunol. Rev. 74:129 (1983).PubMedCrossRefGoogle Scholar
  15. 15.
    D. Gay, P. Maddon, R. Sekaly, M. A. Talle, M. Godfrey, E. Long, G. Goldstein, L. Chess, R. Axel, J. Kappler, and P. Marrack, Functional interaction between human T-cell protein CD4 and the major histocompatibility complex HLA-DR antigen, Nature 328:626 (1987).PubMedCrossRefGoogle Scholar
  16. 16.
    D. Lamarre, A. Ashkenazi, S. Fleury, D. H. Smith, R.-P. Sekaly, and D. J. Capon, The MHC-binding and gpl20-binding functions of CD4 are separable, Science 245:743 (1989).PubMedCrossRefGoogle Scholar
  17. 17.
    R. B. Acres, P. J. Conlon, D. Y. Mochizuki, and B. Gallis, Rapid phosphorylation and modulation of the T4 antigen induced by phorbol myristate acetate or antigen, J. Biol. Chem. 261:16210 (1986).PubMedGoogle Scholar
  18. 18.
    J. A. Hoxie, D. M. Matthews, K. J. Callahan, D. L. Cassel, and R. A. Cooper, Transient modulation and internalization of T4 antigen induced by phorbol esters. J. Immunol. 137:1194 (1986).PubMedGoogle Scholar
  19. 19.
    A. P. Fields, D. P. Bednarik, A. Hess, and W. S. May, Human immunodeficiency virus induces phosphorylation of its cell surface receptor, Nature 333:278 (1988).PubMedCrossRefGoogle Scholar
  20. 20.
    P. J. Maddon, J. S. McDougal, P. R. Clapham, A. G. Dalgleish, S. Jamal, R. A. Weiss, and R. Axel, HIV infection does not require endocytosis of its receptor, CD4, Cell 54:865 (1988).PubMedCrossRefGoogle Scholar
  21. 21.
    B. S Stein, S. D. Gowda, J. D. Lifson, R. C. Penhallow, K. G. Bensch, and E. G. Engleman, pH-independent HIV entry into CD4-positive T cells via virus envelope fusion to the plasma membrane, Cell 49:659 (1987).PubMedCrossRefGoogle Scholar
  22. 22.
    M. 0. McClure, M. Marsh, and R. A. Weiss, Human immunodeficiency virus infection of CD4-bearing cells occurs by a pH-independent mechanism, EMBO J. 7:513 (1988).PubMedGoogle Scholar
  23. 23.
    C. D. Pauza and T. M. Price, Human immunodeficiency virus infection of T cells and monocytes proceeds via receptor-mediated endocytosis, J. Cell Biol. 107:959 (1988).PubMedCrossRefGoogle Scholar
  24. 24.
    J. A Hoxie, J. L. Rackowski, B. S. Haggerty, and G. N. Gaulton, T4 endocytosis and phosphorylation induced by phorbol esters but not by mitogen or HIV infection,J. Immunol. 140:786 (1988).PubMedGoogle Scholar
  25. 25.
    P. Bedinger, A. Moriarty, R. C. von Borstel II, N. J. Donovan, K. S. Steimer, and D. R. Littman, Internalization of the human immunodeficiency virus does not require the cytoplasmic domain of CD4, Nature 334:162 (1988).PubMedCrossRefGoogle Scholar
  26. 26.
    J. S Allan, J. E. Coligan, F. Barin, M. F. McLane, J. G. Sodroski, C. A. Rosen, W. A. Haseltine, T. H. Lee, and M. Essex, Major glycoprotein antigens that induce antibodies in AIDS patients are encoded by HTLV-III, Science 228:1091 (1985).PubMedCrossRefGoogle Scholar
  27. 27.
    F. D. V Ronese, A. L. DeVico, T. D. Copeland, S. Oroszlan, R. C. Gallo, and M. G. Sarngadharan, Characterization of gp41 as the transmembrane protein coded by the HTLV-III/IAV envelope gene, Science 229:1402 (1985).CrossRefGoogle Scholar
  28. 28.
    R. L. Willey, J. S. Bonifacino, B. J. Potts, M. A. Martin, and R. D. Klausner, Biosynthesis, cleavage, and degradation of the human immunodeficiency virus 1 envelope glycoprotein gpl60, Proc. Natl. Acad. Sci. USA 85:9580 (1988).PubMedCrossRefGoogle Scholar
  29. 29.
    S. Modrow, B. H. Hahn, G. M. Shaw, R. C. Gallo, F. Wong-Staal, and H. Wolf, Computer-assisted analysis of envelope protein sequences of seven human immunodeficiency virus isolates: prediction of antigenic epitopes in conserved and variable regions, J. Virol. 61:570 1987).PubMedGoogle Scholar
  30. 30.
    J. M. McCune L. B. Rabin M. B. Feinberg M. Lieberman J. C. Kosek G. R. Reyes and I. L. Weissman Endoproteolytic cleavage of gpl60 is required for the activation of human immudeficiency virus Cell 5355 1988PubMedCrossRefGoogle Scholar
  31. 31.
    A. Pinter, W. J. Honnen, S. A. Tilley, C. Bona, H. Zaghouani, M. K. Gorney, and S. Zolla-Pazner, Oligomeric structure of gp41, the transmembrane protein of human immunodeficiency virus type 1, J. Virol. 63:2674 (1989).PubMedGoogle Scholar
  32. 32.
    J. S. McDougal, M. S. Kennedy, J. M. Sligh, S. P. Cort, A. Mawle, and J. K. A. Nicholson, Binding of HTLV-III/LAV to T4+ T cells by a complex of the llOK viral protein and the T4 molecule, Science 231:382 (1986).PubMedCrossRefGoogle Scholar
  33. 33.
    P. W. Berman, W. M. Nunes, and 0. K. Haffar, Expression of membrane-associated and secreted variants of gpl60 of human immunodeficiency virus type 1 in vitro and in continuous cell lines, J. Virol. 62:3135 (1988).PubMedGoogle Scholar
  34. 34.
    J. D. Lifson, G. R. Reyes, M. S. McGrath, B. S. Stein, and E. G. Engleman, AIDS retrovirus induced cytopathology: giant cell formation and involvement of CD4 antigen, Science 232:1123 (1986).PubMedCrossRefGoogle Scholar
  35. 35.
    J. D. Lifson, M. B. Feinberg, G. R. Reyes, L. Rabin, B. Banapour, S. Chakrabarti, B. Moss, F. Wong-Staal, K. S. Steimer, and E. G. Engleman, Induction of CD4-dependent cell fusion by the HTLV-III/IAV envelope glycoprotein, Nature 323:725 (1986).PubMedCrossRefGoogle Scholar
  36. 36.
    L. A Lasky, G. Nakamura, D. H. Smith, C. Fennie, C. Shimasaki, E. Patzer, P. Berman, T. Gregory, and D. J. Capon, Delineation of a region of the human immunodeficiency virus type 1 gpl20 glycoprotein critical for interaction with the CD4 receptor, Cell 50:975 (1987).PubMedCrossRefGoogle Scholar
  37. 37.
    M. Kowalski, J. Potz, L. Basiripour, T. Dorfman, W. C. Goh, E. Terwilliger, A. Dayton, C. Rosen, W. Haseltine, and J. Sodroski, Functional regions of the envelope glycoprotein of human immunodeficiency virus type 1, Science 237:1351 (1987).PubMedCrossRefGoogle Scholar
  38. 38.
    N. R. Landau, M. Warton, and D. R. Littman, The envelope glycoprotein of the human immunodeficiency virus binds to the immunoglobulin-like domain of CD4, Nature 334:159 (1988).PubMedCrossRefGoogle Scholar
  39. 39.
    A. Peterson and B. Seed Genetic analysis of moclonal antibody and HIV binding sites on the human lymphocyte antigen CD4 Cell 5465 1988PubMedCrossRefGoogle Scholar
  40. 40.
    J. Skehel and M. Waterfield, Studies on the primary structure of the influenza virus hemagglutinin, Proc. Natl. Acad. Sci. USA 72:93 (1982).CrossRefGoogle Scholar
  41. 41.
    M. Homma and M. Ohuchi, Trypsin action on the growth of Sendai virus in tissue culture cells, J. Virol. 12:1257 (1973).Google Scholar
  42. 42.
    A. Scheid and P. W. Choppin, Identification of biological activities of paramyxovirus glycoproteins. Activation of cell fusion, hemolysis, and infectivity by proteolytic cleavage of an inactive precursor protein of Sendai virus, Virology 57:475 (1974).PubMedCrossRefGoogle Scholar
  43. 43.
    A. Scheid and P. W. Choppin, Protease activation mutants of Sendai virus. Activation of biological properties by specific proteases, Virology 69:265 (1976).PubMedCrossRefGoogle Scholar
  44. 44.
    S. Lazarowitz, R. W. Compans, and P. W. Choppin, Proteolytic cleavage of the hemagglutinin polypeptide of influenza virus: function of the uncleaved polypeptide HA, Virology 68:199 (1973).CrossRefGoogle Scholar
  45. 45.
    H.-D. Klenk, R. Rott, M. Orlich, and J. Blodorn, Activation of influenza A viruses by trypsin treatment, Virology 68:426 (1975).PubMedCrossRefGoogle Scholar
  46. 46.
    C. Blobel, Intracellular protein topogenesis, Proc. Natl. Acad. Sci. USA 77:1496 (1980).PubMedCrossRefGoogle Scholar
  47. 47.
    S.J. Singer, P. A. Maher, and M. P. Yaffe, On the translocation of proteins across membranes, Proc. Natl. Acad. Sci. USA 84:1015 (1987).PubMedCrossRefGoogle Scholar
  48. 48.
    J. J. Skehel, P. Bayley, E. Brown, S. Martin, M. Waterfield, J. White, I. Wilson, and D. Wiley, Changes in the conformation of influenza virus hemagglutinin at the pH optimum of virus-mediated membrane fusion, Proc. Natl. Acad. Sci. USA 79:968 (1982).PubMedCrossRefGoogle Scholar
  49. 49.
    T. Maeda, K. Kawasaki, and S.-I. Ohnishi, Interaction of influenza virus hemagglutinin with target lipids is a key step in virus-induced hemolysis and fusion at pH 5.2, Proc. Natl. Acad. Sci. USA 78:4133 (1981).PubMedCrossRefGoogle Scholar
  50. 50.
    G. VanMeer, J. Davoust, and K. Simons, Parameters affecting low pH-mediated fusion of liposomes with the plasma membrane of cells infected with influenza virus, Biochemistry 24:3593 (1985).CrossRefGoogle Scholar
  51. 51.
    A. M. Aywood, Fusion of Sendai viruses with model membranes, J. Mol. Biol. 87:625 (1974).CrossRefGoogle Scholar
  52. 52.
    J. White and A. Helenius, pH-dependent fusion between the Semliki Forest virus membrane and liposomes, Proc. Natl. Acad. Sci. USA 77:3273 (1980).PubMedCrossRefGoogle Scholar
  53. 53.
    J. J. Mooney, J. M. Dalrymple, C. R. Alving, and P. K. Russell, Interaction of Sindbis virus with liposomal model membranes, J. Virol. 15:225 (1975).PubMedGoogle Scholar
  54. 54.
    R. K. Cheule, Fusion of Sindbis virus with model membranes containing phosphatidylethanolamine: implications for protein induced membrane fusion, Biochim. Biophys. Acta 899:185 (1987).CrossRefGoogle Scholar
  55. 55.
    L. V. Chernmordik, G. B. Melikyan, and Y. A. Chizmadzhev, Biomembrane fusion: a new concept derived from model studies using two interacting planar lipid bilayers, Biochim. Biophvs. Acta 906:309 (1987).Google Scholar
  56. 56.
    R. P. Rand and V. A. Parsegian, Mimicry and mechanism in phospholipid models of membrane fusion, Ann. Rev. Physiol. 48:201 (1986).CrossRefGoogle Scholar
  57. 57.
    D. M. LeNeveu, R. P. Rand, V. A. Parsegian, and D. Gingell, Measurement of forces between lecithin bilayers, Nature 259:601 (1976).PubMedCrossRefGoogle Scholar
  58. 58.
    D. M. LeNeveu, R. P. Rand, V. A. Parsegian, and D. Gingell, Measurement and modification of forces between lecithin bilayers, Biophvs. J. 18:209 (1977).CrossRefGoogle Scholar
  59. 59.
    L. J. Lis, M. McAlister, N. Fuller, R. P. Rand, and V. A. Parsegian, Interactions between neutral phospholipid bilayer membranes, Biophvs. J. 37:657 (1982).Google Scholar
  60. 60.
    P. Claesson, A. M. Carmona-Ribeiro, and K. J. Kurihara, Dihexadecyl phosphate monolayers — intralayer and interlayer interactions, J. Phvs. Chem. 93:p917 (1989).CrossRefGoogle Scholar
  61. 61.
    J. N. Israelachvili and R. M. Pashley, The hydrophobic interaction is long range, decaying exponentially with distance, Nature 300:p341 (1982).CrossRefGoogle Scholar
  62. 62.
    R. M. Ashley, P. M. McGuiggan, B. W. Ninham, and D. F. Evans, Attractive forces between uncharged hydrophobic surfaces: direct measurements in aqueous solution, Science 229:1088 (1985).CrossRefGoogle Scholar
  63. 63.
    P. M. Caesson, C. E. Blom, P. C. Herder, and B. W. Ninham, Interactions between water-stable hydrophobic Langmuir-Blodgett monolayers on mica, J. Colloid Interface Sci. 114:234 (1986).CrossRefGoogle Scholar
  64. 64.
    R. Rand, Interacting phospholipid bilayers: measured forces and induced structural changes, Ann. Rev. Biophys. Bioeng. 10:277 (1981).CrossRefGoogle Scholar
  65. 65.
    C. A. Helm, J. N. Israelachvili, and P. M. McGuiggan, Molecular mechanisms and forces involved in the adhesion and fusion of amphiphilic bilayers, Science 246:919 (1989).PubMedCrossRefGoogle Scholar
  66. 66.
    P. R. Lapham, J. N. Weber, D. Whitby, K. Mcintosh, A. G. Dalgleish, P. J. Maddon, K. C. Deen, R. W. Sweet, and R. A. Weiss, Soluble CD4 blocks the infectivity of diverse strains of HIV and SIV for T cells and monocytes but not for brain and muscle cells, Nature 337:368 (1989).CrossRefGoogle Scholar
  67. 67.
    M. Tateno, F. Gonzalez-Scarano, and J. A. Levy, Human immunodeficiency virus can infect CD4-negative human fibroblastoid cells, Proc. Natl. Acad. Sci. USA 86:4287 (1989).PubMedCrossRefGoogle Scholar
  68. 68.
    J. Homsy, M. Meyer, M. Tateno, S. Clarkson, and J. A. Levy, The Fc and not CD4 receptor mediates antibody enhancement of HIV infection in human cells, Science 244:1357 (1989).PubMedCrossRefGoogle Scholar
  69. 69.
    I. Mellman and H. Plutner, Internalization and degradation of macrophage Fc receptors bound to polyvalent immune complexes, J. Cell Biol. 98:1170 (1984).PubMedCrossRefGoogle Scholar
  70. 70.
    D. Zagury, J. Bernard, R. Leonard, R. Cheynier, M. Feldman, P. S. Sarin, and R. C. Gallo, Long-term cultures of HTLV-III-infected T cells: a model of cytopathology of T-cell depletion in AIDS, Science 231:850 (1986).PubMedCrossRefGoogle Scholar
  71. 71.
    J. B. Ma Golick, D. J. Volkman, T. M. Folks, and A. S. Fauci, Amplification of HTLV-III/LAV infection by antigen-induced activation of T cells and direct suppression by virus of lymphocyte blastogenic responses, J. Immunol. 138:1719 (1987).Google Scholar
  72. 72.
    S. D Gowda, B. S. Stein, N. Mohagheghpour, C. J. Benike, and E. G. Engleman, Evidence that T cell activation is required for HIV-1 entry in CD4+ lymphocytes, J. Immunol. 142:773 (1989).PubMedGoogle Scholar
  73. 73.
    N. Mohagheghpour, R. Chakrabarti, B. S. Stein, S. D. Gowda, and E. G. Engleman, Uninfected resting CD4+ T cells require early activation events to fuse with HIV-1 infected T cells, FASEB J. 3:1280 (1989).Google Scholar
  74. 74.
    N. Isakov, M. I. Mally, W. Scholz, and A. Altman,T-lymphocyte activation: the role of protein kinase C and the bifurcating inositol phospholipid signal transduction pathway, Immunol. Rev. 95:89 (1987).PubMedCrossRefGoogle Scholar
  75. 75.
    S. M. Schittman, M. C. Psallidopoulos, H. C. Lane, L. Thompson, M. Baseler, F. Massari, C. H. Fox, N. P. Salzman, and A. S. Fauci, The reservoir for HIV-1 in human peripheral blood is a T cell that maintains expression of CD4, Science 245:305 (1989).CrossRefGoogle Scholar
  76. 76.
    D.D. Ho, T. Moudgil, and M. Alam, Quantitation of human immunodeficiency virus type 1 in the blood of infected persons, New Engl. J. Med. 321:1621 (1989).PubMedCrossRefGoogle Scholar
  77. 77.
    R. W. Coombs, A. C. Collier, J.-P. Allain, B. Nikora, M. Leuther, G. F. Gjerset, and L. Corey, Plasma viremia in human immunodeficiency virus infection, New Engl. J. Med. 321:1627 (1989).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Barry S. Stein
    • 1
  • Edgar G. Engleman
    • 1
  1. 1.Stanford Blood CenterStanford University School of MedicinePalo AltoUSA

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