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
2024-12-04
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;
    [Google Scholar]
  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 Brown F., Burton D. R., Collier J., Mekalonos J., Norrby E. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  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]
/content/journal/jgv/10.1099/vir.0.80439-0
Loading
/content/journal/jgv/10.1099/vir.0.80439-0
Loading

Data & Media loading...

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