1887

Abstract

The C-terminal tail of the gp41 transmembrane glycoprotein of the human immunodeficiency virus type 1 (HIV-1) virion is usually thought to be inside the virion, but it has been shown recently that part of the tail is exposed on the virion exterior. Here, using a panel of antibodies, it was demonstrated that the same part of the tail is exposed on the surface of HIV-1-infected C8166 lymphoblastoid cells and HeLa cells infected with a gp41-expressing vaccinia virus recombinant. Both types of infected cell failed to react with p17 matrix protein-specific IgGs until permeabilized with saponin, confirming the integrity of the plasma membrane. Cell-surface exposure of the gp41 tail was independently demonstrated by inhibition of HIV-1-mediated cell–cell fusion by one of the gp41 tail-specific antibodies. These data also implicate the exposed region of the gp41 C-terminal tail either directly or indirectly in the viral fusion process. Its surface exposure suggests that the gp41 C-terminal tail may be a candidate for immune intervention or chemotherapy of infection.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.80439-0
2005-01-01
2019-11-20
Loading full text...

Full text loading...

/deliver/fulltext/jgv/86/1/vir860131.html?itemId=/content/journal/jgv/10.1099/vir.0.80439-0&mimeType=html&fmt=ahah

References

  1. Abacioglu, Y. H., Fouts, T. R., Laman, J. D., Classen, E., Pincus, S. H., Moore, J. P., Roby, C. A., Kamin-Lewis, R. & Lewis, G. K. ( 1994; ). Epitope mapping and topology of baculovirus-expressed HIV-1 gp160 determined with a panel of murine monoclonal antibodies. AIDS Res Hum Retrovir 10, 371–381.[CrossRef]
    [Google Scholar]
  2. Armstrong, S. J., McInerney, T. L., McLain, L., Wahren, B., Hinkula, J., Levi, M. & Dimmock, N. J. ( 1996; ). Two neutralizing anti-V3 monoclonal antibodies act by affecting different functions of human immunodeficiency virus type 1. J Gen Virol 77, 2931–2941.[CrossRef]
    [Google Scholar]
  3. Berlioz-Torrent, C., Shacklett, B. L., Erdtmann, L., Delamarre, L., Bouchaert, I., Sonigo, P., Dokhelar, M. C. & Benarous, R. ( 1999; ). Interactions of the cytoplasmic domains of human and simian retroviral transmembrane proteins with components of the clathrin adapter complexes modulate intracellular and cell surface expression of envelope glycoprotein. J Virol 73, 1350–1361.
    [Google Scholar]
  4. Bukrinskaya, A. G. & Sharova, N. K. ( 1990; ). Unusual features of protein interaction in human immunodeficiency virus (HIV) virions. Arch Virol 110, 287–293.[CrossRef]
    [Google Scholar]
  5. Buratti, E., McLain, L., Tisminetzky, S. G., Cleveland, S. M., Dimmock, N. J. & Baralle, F. E. ( 1998; ). The neutralizing antibody response against a conserved region of HIV-1 gp41 (amino acid residues 731–752) is uniquely directed against a conformational epitope. J Gen Virol 79, 2709–2716.
    [Google Scholar]
  6. Burton, D. R., Pyati, J., Koduri, R. & 15 other authors ( 1994; ). Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody. Science 266, 1024–1027.[CrossRef]
    [Google Scholar]
  7. Caffrey, M., Cai, M., Kaufman, J., Stahl, S. J., Wingfield, P. T., Covell, D. G., Gronenborn, A. M. & Clore, G. M. ( 1998; ). Three-dimensional solution of the 44 kDa ectodomain of SIV gp41. EMBO J 17, 4572–4584.[CrossRef]
    [Google Scholar]
  8. Celma, C. C. P., Manrique, J. M., Affranchino, J. L., Hunter, E. & González, S. A. ( 2001; ). Domains in the simian immunodeficiency virus gp41 cytoplasmic tail required for envelope incorporation into particles. Virology 283, 253–261.[CrossRef]
    [Google Scholar]
  9. Chan, D. C., Fass, D., Berger, J. & Kim, P. S. ( 1997; ). Core structure of gp41 from the HIV envelope glycoprotein. Cell 89, 263–273.[CrossRef]
    [Google Scholar]
  10. Chanh, T. C., Dreesman, G., Kanda, P., Linette, G. P., Sparrow, J. T., Ho, D. D. & Kennedy, R. C. ( 1986; ). Induction of anti-HIV neutralizing antibodies by synthetic peptides. EMBO J 5, 3065–3071.
    [Google Scholar]
  11. Cheung, L. H. Y. ( 2002; ). Antibody specificities stimulated by cowpea mosaic virus–HIV chimeras. PhD thesis, University of Warwick, Coventry, UK.
  12. Cleveland, S. M. ( 1999; ). HIV-1 specific antibody responses to a plant virus–HIV chimera. PhD thesis, University of Warwick, Coventry, UK.
  13. Cleveland, S. M., Buratti, E., Jones, T. D., North, P., Baralle, F. E., McLain, L., McInerney, T. L., Durrani, Z. & Dimmock, N. J. ( 2000a; ). Immunogenic and antigenic dominance of a non-neutralizing epitope over a highly conserved neutralizing epitope in the gp41 transmembrane envelope glycoprotein of HIV-1: its deletion leads to a strong neutralizing antibody response. Virology 266, 66–78.[CrossRef]
    [Google Scholar]
  14. Cleveland, S. M., Jones, T. D. & Dimmock, N. J. ( 2000b; ). Properties of a neutralizing antibody that recognizes a conformational form of epitope ERDRD in the C-terminal tail of human immunodeficiency virus type 1. J Gen Virol 81, 1251–1260.
    [Google Scholar]
  15. Cleveland, S. M., McLain, L., Cheung, L., Jones, T., Hollier, M. & Dimmock, N. J. ( 2003; ). A region of the C-terminal tail of the gp41 envelope glycoprotein of human immunodeficiency virus type 1 contains a neutralizing epitope: evidence for its exposure on the surface of the virion. J Gen Virol 84, 591–602.[CrossRef]
    [Google Scholar]
  16. Cosson, P. ( 1996; ). Direct interaction between the envelope and matrix proteins of HIV-1. EMBO J 15, 5783–5788.
    [Google Scholar]
  17. Dalgleish, A. G., Chanh, T. C., Kennedy, R. C., Kanda, P., Clapham, P. R. & Weiss, R. A. ( 1988; ). Neutralization of diverse strains of HIV-1 by monoclonal antibodies raised against a gp41 synthetic peptide. Virology 165, 209–215.[CrossRef]
    [Google Scholar]
  18. Di Fiore, P. P. & Gill, G. N. ( 1999; ). Endocytosis and mitogenic signalling. Curr Opin Cell Biol 11, 483–488.[CrossRef]
    [Google Scholar]
  19. Dorfman, T., Mammano, F., Haseltine, W. A. & Göttlinger, H. G. ( 1994; ). Role of the matrix protein in the virion association of the human immunodeficiency virus type 1 envelope protein. J Virol 68, 1689–1696.
    [Google Scholar]
  20. Durrani, Z., McInerney, T. L., McLain, L., Jones, T., Bellaby, T., Brennan, F. R. & Dimmock, N. J. ( 1998; ). Intranasal immunization with a plant virus expressing a peptide from HIV-1 gp41 stimulates better mucosal and systemic HIV-1-specific IgA and IgG than oral immunization. J Immunol Methods 220, 93–103.[CrossRef]
    [Google Scholar]
  21. Edwards, T. G., Hoffman, T. L., Baribaud, F. & 7 other authors ( 2001; ). Relationships between CD4 independence, neutralization sensitivity, and exposure of a CD4-induced epitope in a human immunodeficiency virus type 1 envelope protein. J Virol 75, 5230–5239.[CrossRef]
    [Google Scholar]
  22. Edwards, T. G., Wyss, S., Reeves, J. D., Zolla-Pazner, S., Hoxie, J. A., Doms, R. W. & Baribaud, F. ( 2002; ). Truncation of the cytoplasmic domain induces exposure of conserved regions in the ectodomain of human immunodeficiency virus type 1 envelope protein. J Virol 76, 2683–2691.[CrossRef]
    [Google Scholar]
  23. Evans, D. J., McKeating, J. A., Meredith, J. M., Burke, K. L., Katrak, K., Ferguson, M., Minor, P. D., Weiss, R. A. & Almond, J. W. ( 1989; ). An engineered poliovirus chimaera elicits broadly reactive HIV-1 neutralizing antibodies. Nature 339, 385–388.[CrossRef]
    [Google Scholar]
  24. Ferns, R. B., Tedder, R. S. & Weiss, R. A. ( 1987; ). Characterization of monoclonal antibodies against the human immunodeficiency virus (HIV) gag products and their use in monitoring HIV isolate variation. J Gen Virol 68, 1543–1551.[CrossRef]
    [Google Scholar]
  25. Freed, E. O. & Martin, M. A. ( 1995a; ). The role of the human immunodeficiency virus type 1 envelope glycoproteins in virus infection. J Biol Chem 270, 23883–23886.[CrossRef]
    [Google Scholar]
  26. Freed, E. O. & Martin, M. A. ( 1995b; ). Virion incorporation of envelope glycoproteins with long but not short cytoplasmic tails is blocked by specific single amino acid substitutions in the human immunodeficiency virus type 1 matrix. J Virol 69, 1984–1989.
    [Google Scholar]
  27. Freed, E. O. & Martin, M. A. ( 1996; ). Domains on the human immunodeficiency virus type 1 matrix and gp41 cytoplasmic tail required for envelope incorporation into virions. J Virol 70, 341–351.
    [Google Scholar]
  28. Fultz, P. N., Vance, P. J., Endres, M. J. & 8 other authors ( 2001; ). In vivo attenuation of simian immunodeficiency virus by disruption of a tyrosine-dependent sorting signal in the envelope glycoprotein cytoplasmic tail. J Virol 75, 278–291.[CrossRef]
    [Google Scholar]
  29. Gallaher, W. R., Ball, J. M., Garry, R. F., Griffin, M. C. & Montelaro, R. C. ( 1989; ). A general model for the transmembrane proteins of HIV and other retroviruses. AIDS Res Hum Retrovir 5, 431–440.[CrossRef]
    [Google Scholar]
  30. Heilker, R., Spiess, M. & Crottet, P. ( 1999; ). Recognition of sorting signals by clathrin adapters. Bioessays 7, 558–567.
    [Google Scholar]
  31. Ho, D. D., Sarngadharan, M. G., Hirsch, M. S., Schooley, R. T., Rota, T. R., Kennedy, R. C., Chanh, T. C. & Sato, V. L. ( 1987; ). Human immunodeficiency virus neutralizing antibodies recognise several conserved domains on the envelope glycoprotein. J Virol 61, 2024–2028.
    [Google Scholar]
  32. Iwatani, Y., Ueno, T., Nishimura, A., Zhang, X., Hattori, T., Ishimoto, A., Ito, M. & Sakai, H. ( 2001; ). Modification of virus infectivity by cytoplasmic tail of HIV-1 TM protein. Virus Res 74, 75–87.[CrossRef]
    [Google Scholar]
  33. Jackson, N. A. C., Levi, M., Wahren, B. & Dimmock, N. J. ( 1999; ). Mechanism of action of a 17 amino acid microantibody specific for the V3 loop that neutralizes free HIV-1 virions. J Gen Virol 80, 225–236.
    [Google Scholar]
  34. Kennedy, R. C., Henkel, R. D., Pauletti, D., Allan, J. S., Lee, T. H., Essex, M. & Dreesman, G. R. ( 1986; ). Antiserum to a synthetic peptide recognizes the HTLV-III envelope glycoprotein. Science 231, 1556–1559.[CrossRef]
    [Google Scholar]
  35. Levy, J. A. ( 1998; ). HIV and the Pathogenesis of AIDS, 2nd edn. Herndon, VA: ASM Press.
  36. Malashkevitch, V. N., Chan, D. C., Chutowski, C. T. & Kim, P. S. ( 1998; ). Crystal structure of the simian immunodeficiency virus (SIV) gp41 core: conserved helical interactions underlie the broad inhibitory activity of gp41 peptides. Proc Natl Acad Sci U S A 95, 9134–9139.[CrossRef]
    [Google Scholar]
  37. Mammano, F., Kondo, E., Sodroski, J., Bukovsky, A. & Göttlinger, H. G. ( 1995; ). Rescue of human immunodeficiency virus type 1 matrix protein mutants by envelope glycoproteins with short cytoplasmic tails. J Virol 69, 3824–3830.
    [Google Scholar]
  38. Manrique, J. M., Celma, C. C. P., Affranchino, J. L., Hunter, E. & González, S. A. ( 2001; ). Small variations in the length of the cytoplasmic domain of the simian immunodeficiency virus transmembrane protein drastically affect envelope incorporation and virus entry. AIDS Res Hum Retrovir 17, 1615–1624.[CrossRef]
    [Google Scholar]
  39. McInerney, T. L., McLain, L., Armstrong, S. J. & Dimmock, N. J. ( 1997; ). A human IgG1 (b12) specific for the CD4 binding site of HIV-1 neutralizes by inhibiting the virus fusion entry process, but b12 Fab neutralizes by inhibiting a post-fusion event. Virology 233, 313–326.[CrossRef]
    [Google Scholar]
  40. McLain, L. & Dimmock, N. J. ( 1994; ). Single- and multi-hit kinetics of immunoglobulin G neutralization of human immunodeficiency virus type 1 by monoclonal antibodies. J Gen Virol 75, 1457–1460.[CrossRef]
    [Google Scholar]
  41. McLain, L., Porta, C., Lomonossoff, G. P., Durrani, Z. & Dimmock, N. J. ( 1995; ). Human immunodeficiency virus type 1 neutralizing antibodies raised to a gp41 peptide expressed on the surface of a plant virus. AIDS Res Hum Retrovir 11, 327–334.[CrossRef]
    [Google Scholar]
  42. McLain, L., Durrani, Z., Wisniewski, L. A., Porta, C., Lomonossoff, G. P. & Dimmock, N. J. ( 1996a; ). A plant virus–HIV-1 chimera stimulates antibody that neutralizes HIV-1. In Vaccines 96, pp. 311–316. Edited by F. Brown, D. R. Burton, J. Collier, J. Mekalonos & E. Norrby. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  43. McLain, L., Durrani, Z., Wisniewski, L. A., Porta, C., Lomonossoff, G. P. & Dimmock, N. J. ( 1996b; ). Stimulation of neutralizing antibodies to human immunodeficiency virus type 1 in three strains of mice immunized with a 22-mer amino acid peptide expressed on the surface of a plant virus. Vaccine 14, 799–810.[CrossRef]
    [Google Scholar]
  44. McLain, L., Brown, J. L., Cheung, L., Reading, S. A., Parry, C., Jones, T. D., Cleveland, S. M. & Dimmock, N. J. ( 2001; ). Different effects of a single amino acid substitution on three epitopes in the gp41 C-terminal loop of a neutralizing antibody escape mutant of human immunodeficiency virus type 1. Arch Virol 146, 157–166.[CrossRef]
    [Google Scholar]
  45. Mulligan, M. J., Yamshchikov, G. V., Ritter, G. D., Gao, F., Jin, M. J., Nail, C. D., Spies, C. P., Hahn, B. H. & Compans, R. W. ( 1992; ). Cytoplasmic domain truncation enhances fusion activity by the exterior glycoprotein complex of human immunodeficiency virus type 2 in certain cell types. J Virol 66, 3971–3975.
    [Google Scholar]
  46. Murakami, T. & Freed, E. O. ( 2000a; ). Genetic evidence for an interaction between human immunodeficiency virus type 1 matrix protein and α-helix 2 of the gp41 cytoplasmic tail. J Virol 74, 3548–3554.[CrossRef]
    [Google Scholar]
  47. Murakami, T. & Freed, E. O. ( 2000b; ). The long cytoplasmic tail of gp41 is required in a cell type-dependent manner for HIV-1 envelope glycoprotein incorporation into virions. Proc Natl Acad Sci U S A 97, 343–348.[CrossRef]
    [Google Scholar]
  48. Muster, T., Steindl, F., Purtscher, M., Trkola, A., Klima, A., Himmler, G., Rüker, F. & Katinger, H. ( 1993; ). A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. J Virol 67, 6642–6647.
    [Google Scholar]
  49. Newton, S. M. C., Joys, T. M., Anderson, S. A., Kennedy, R. C., Hovi, M. E. & Stocker, B. A. D. ( 1995; ). Expression and immunogenicity of an 18-residue epitope of HIV-1 gp41 inserted in the flagellar protein of a Salmonella live vaccine. Res Microbiol 146, 203–216.[CrossRef]
    [Google Scholar]
  50. Nixon, D. F., Townsend, A. R. M., Elvin, J. G., Rizza, C. R., Gallwey, J. & McMichael, A. J. ( 1988; ). HIV-1 gag-specific cytotoxic T lymphocytes defined with recombinant vaccinia virus and synthetic peptides. Nature 336, 484–489.[CrossRef]
    [Google Scholar]
  51. Piller, S. C., Dubay, J. W., Derdeyn, C. A. & Hunter, E. ( 2000; ). Mutational analysis of conserved domains within the cytoplasmic tail of gp41 from human immunodeficiency virus type 1: effects on glycoprotein incorporation and infectivity. J Virol 74, 11717–11723.[CrossRef]
    [Google Scholar]
  52. Porta, C. & Lomonossoff, G. P. ( 1998; ). Scope for plant viruses to present epitopes from animal pathogens. Rev Med Virol 8, 25–41.[CrossRef]
    [Google Scholar]
  53. Ratner, L., Haseltine, W., Patarca, R. & 16 other authors ( 1985; ). Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature 313, 277–284.[CrossRef]
    [Google Scholar]
  54. Reading, S. A., Heap, C. J. & Dimmock, N. J. ( 2003; ). A novel monoclonal antibody specific for the C-terminal tail of the gp41 envelope transmembrane protein of human immunodeficiency virus type 1 that preferentially neutralizes virus after it has attached to the target cell and inhibits the production of infectious progeny. Virology 315, 362–372.[CrossRef]
    [Google Scholar]
  55. Sattentau, Q. J., Zolla-Pazner, S. & Poignard, P. ( 1995; ). Epitope exposure on functional, oligomeric HIV-1 gp41 molecules. Virology 206, 713–717.[CrossRef]
    [Google Scholar]
  56. Sauter, M. M., Pelchen-Matthews, A., Bron, R. & 8 other authors ( 1996; ). An internalization signal in the simian immunodeficiency virus transmembrane protein cytoplasmic domain modulates expression of envelope glycoproteins on the cell surface. J Cell Biol 132, 795–811.[CrossRef]
    [Google Scholar]
  57. Sodroski, J., Goh, W. C., Rosen, C., Campbell, K. & Haseltine, W. A. ( 1986; ). Role of the HTLV-III/LAV envelope in syncytium formation and cytopathicity. Nature 322, 470–474.[CrossRef]
    [Google Scholar]
  58. Spies, C. P., Ritter, G. D., Mulligan, M. J. & Compans, R. W. ( 1994; ). Truncation of the cytoplasmic domain of the simian immunodeficiency virus envelope glycoprotein alters the conformation of the external domain. J Virol 68, 585–591.
    [Google Scholar]
  59. Tan, K., Liu, J.-H., Wang, J.-H., Shen, S. & Liu, M. ( 1997; ). Atomic structure of a thermostable subdomain of HIV-1 gp41. Proc Natl Acad Sci U S A 94, 12303–12308.[CrossRef]
    [Google Scholar]
  60. Vella, C., Ferguson, M., Dunn, G., Meloen, R., Langedijk, H., Evans, D. & Minor, P. D. ( 1993; ). Characterization and primary structure of a human immunodeficiency virus type 1 (HIV-1) neutralization domain as presented by a poliovirus type 1/HIV-1 chimera. J Gen Virol 74, 2603–2607.[CrossRef]
    [Google Scholar]
  61. Vzorov, A. N. & Compans, R. W. ( 2000; ). Effect of the cytoplasmic domain of the simian immunodeficiency virus envelope protein on incorporation of heterologous envelope proteins and sensitivity to neutralization. J Virol 74, 8219–8225.[CrossRef]
    [Google Scholar]
  62. Weissenhorn, W., Dessen, A., Harrison, S. C., Skehel, J. J. & Wiley, D. C. ( 1997; ). Atomic structure of the ectodomain from HIV-1 gp41. Nature 387, 426–430.[CrossRef]
    [Google Scholar]
  63. Wilk, T., Pfeiffer, T. & Bosch, V. ( 1992; ). Retained in vitro infectivity and cytopathogenicity of HIV-1 despite truncation of the C-terminal tail of the env gene product. Virology 189, 167–177.[CrossRef]
    [Google Scholar]
  64. Wyma, D. J., Kotov, A. & Aiken, C. ( 2000; ). Evidence for a stable interaction of gp41 with Pr55Gag in immature human immunodeficiency virus type 1 particles. J Virol 74, 9381–9387.[CrossRef]
    [Google Scholar]
  65. Yu, X., Yuan, X., McLane, M. F., Lee, T.-H. & Essex, M. ( 1993; ). Mutations in the cytoplasmic domain of human immunodeficiency virus type 1 transmembrane protein impair the incorporation of Env proteins into mature virions. J Virol 67, 213–221.
    [Google Scholar]
  66. Zingler, K. & Littman, D. R. ( 1993; ). Truncation of the cytoplasmic domain of the simian immunodeficiency virus envelope glycoprotein increases Env incorporation into particles and fusogenicity and infectivity. J Virol 67, 2824–2831.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.80439-0
Loading
/content/journal/jgv/10.1099/vir.0.80439-0
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error