1887

Abstract

Fusion of CD4 cells by HIV-1 envelope proteins (Env) is a mechanism of virus spread and cell damage. Production of antibodies able to influence cell–cell fusion may affect the course of the infection. The effect of sera from 49 HIV-1-positive patients was tested on an fusion assay using Env-expressing and normal Jurkat T cells labelled with DiI and DiO dyes, and flow cytometry for quantification of cell–cell fusion. Sera varied in their activity on fusion: 69·4 % inhibited, 24·5 % had no effect and 6·1 % enhanced cell fusion. Fusion activity correlated positively with the CD4 T-cell count and inversely with the viral load. Removal of IgG or IgM from sera reduced or eliminated inhibition and enhancing activities, respectively. Antibodies with inhibitory activity predominate in early and intermediate stages of infection, whereas loss of inhibition or enhancement of fusion correlates with progression to AIDS.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.80635-0
2005-07-01
2019-10-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/86/7/vir861961.html?itemId=/content/journal/jgv/10.1099/vir.0.80635-0&mimeType=html&fmt=ahah

References

  1. Allaway, G. P., Ryder, A. M., Beaudry, G. A. & Maddon, P. J. ( 1993; ). Synergistic inhibition of HIV-1 envelope-mediated cell fusion by CD4-based molecules in combination with antibodies to gp120 or gp41. AIDS Res Hum Retroviruses 9, 581–587.[CrossRef]
    [Google Scholar]
  2. Amendola, A., Gougeon, M. L., Poccia, F., Bondurand, A., Fesus, L. & Piacentini, M. ( 1996; ). Induction of “tissue” transglutaminase in HIV patogenesis: evidence for high rate apoptosis of CD4+ T lymphocytes and accessory cells in lymphoid tissues. Proc Natl Acad Sci U S A 93, 11057–11062.[CrossRef]
    [Google Scholar]
  3. Asherson, R. A. & Shoenfeld, V. ( 2003; ). Human immunodeficiency virus infection, antiphospholipid antibodies, and the antiphospholipid syndrome. J Rheumatol 30, 214–219.
    [Google Scholar]
  4. Blaak, H., van't Wout, A. B., Brouwer, M., Hooibrink, B., Hovenkamp, E. & Schuitemaker, H. ( 2000; ). In vivo HIV-1 infection of CD45RA+CD4+ T cells is established primarily by syncytium-inducing variants and correlates with the rate of CD4+ T cell decline. Proc Natl Acad Sci U S A 97, 1269–1274.[CrossRef]
    [Google Scholar]
  5. Budka, H. ( 1986; ). Multinucleated giant cells in brain: a hallmark of the acquired immune deficiency syndrome (AIDS). Acta Neuropathol 69, 253–258.[CrossRef]
    [Google Scholar]
  6. Cao, J., Park, I. W., Cooper, A. & Sodroski, J. ( 1996; ). Molecular determinants of acute single-cell lysis by human immunodeficiency virus type 1. J Virol 70, 1340–1354.
    [Google Scholar]
  7. Castedo, M., Roumier, T., Blanco, J. & 18 other authors ( 2002; ). Sequential involvement of Cdk1, mTOR and p53 in apoptosis induced by the HIV-1 envelope. EMBO J 21, 4070–4080.[CrossRef]
    [Google Scholar]
  8. Castro, K. G., Ward, J. W., Slutsker, L., Buehler, J. W., Jaffe, H. W. & Berkelman, R. L. ( 1993; ). Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. Morbid Mortal Wkly Rep 41, 1–19.
    [Google Scholar]
  9. Cecilia, D., Kleeberger, C., Muñoz, A., Giorgi, J. V. & Zolla-Pazner, S. ( 1999; ). A longitudinal study of neutralizing antibodies and disease progression in HIV-1-infected subjects. J Infect Dis 179, 1365–1374.[CrossRef]
    [Google Scholar]
  10. Connor, R. I. & Ho, D. D. ( 1994; ). Human immunodeficiency virus type 1 variants with increased replicative capacity develop during the asymptomatic stage before disease progression. J Virol 68, 4400–4408.
    [Google Scholar]
  11. Connor, R. I., Mohri, H., Cao, Y. & Ho, D. D. ( 1993; ). Increased viral burden and cytopathicity correlate temporally with CD4+ T-lymphocyte decline and clinical progression in human immunodeficiency virus type 1-infected individuals. J Virol 67, 1772–1777.
    [Google Scholar]
  12. Etemad-Moghadam, B., Rhone, D., Steenbeke, T. & 9 other authors ( 2001; ). Membrane-fusing capacity of the human immunodeficiency virus envelope proteins determines the efficiency of CD4+ T-cell depletion in macaques infected by a simian-human immunodeficiency virus. J Virol 75, 5646–5655.[CrossRef]
    [Google Scholar]
  13. Ferri, K. F., Jacotot, E., Blanco, J. & 8 other authors ( 2000; ). Apoptosis control in syncytia induced by the HIV type 1-envelope glycoprotein complex: role of mitochondria and caspases. J Exp Med 192, 1081–1092.[CrossRef]
    [Google Scholar]
  14. Frankel, S. S., Wenig, B. M., Burke, A. P., Manan, P., Thompson, L. D., Abbondazo, S. L., Nelson, A. M., Pope, M. & Steinman, R. M. ( 1996; ). Replication of HIV-1 in dendritic cell-derived syncytia at the mucosal surface of the adenoid. Science 272, 115–117.[CrossRef]
    [Google Scholar]
  15. Gudiño, J. C. & Soler, C. ( 2000; ). Detección de virus subtipo B del HIV-1 mediante el análisis de restricción de amplicones de gag con la enzima Bst Xi (REA-PCR). Abstracts from the I Congreso Nacional de la Rama de Bioquímica y Biología Molecular de Virus de la Sociedad Mexicana de Bioquímica. Rev Biomed 11, 135–154.
    [Google Scholar]
  16. Gummurulu, S., Kinsey, M. C. & Emerman, M. ( 2000; ). An in vitro rapid-turnover assay for human immunodeficiency virus type 1 replication selects for cell-to-cell spread of virus. J Virol 74, 10882–10891.[CrossRef]
    [Google Scholar]
  17. Gupta, P., Balachandran, R., Ho, M., Enrico, A. & Rinaldo, C. ( 1989; ). Cell-to-cell transmission of human immunodeficiency virus type 1 in the presence of azidothymidine and neutralizing antibody. J Virol 63, 2361–2365.
    [Google Scholar]
  18. Hioe, C. E., Bastiani, L., Hildreth, J. E. & Zolla-Pazner, S. ( 1998; ). Role of cellular adhesion molecules in HIV type 1 infection and their impact on virus neutralization. AIDS Res Hum Retroviruses 14, S247–S254.
    [Google Scholar]
  19. Huerta, L., Lamoyi, E., Báez-Saldaña, A. & Larralde, C. ( 2002; ). Human immunodeficiency virus envelope-dependent cell-cell fusion: a quantitative fluorescence cytometric assay. Cytometry 47, 100–106.[CrossRef]
    [Google Scholar]
  20. Kilby, J. M., Hopkins, S., Venetta, T. M. & 12 other authors ( 1998; ). Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nat Med 4, 1302–1307.[CrossRef]
    [Google Scholar]
  21. Koenig, S., Gendelman, H. E., Orenstein, J. M. & 7 other authors ( 1986; ). Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science 233, 1089–1093.[CrossRef]
    [Google Scholar]
  22. Laurent-Crawford, A. G., Krust, B., Muller, S., Riviere, Y., Rey-Cuille, M. A., Bechet, J. M., Montagnier, L. & Hovanessian, A. G. ( 1991; ). The cytopathic effect of HIV is associated with apoptosis. Virology 185, 829–839.[CrossRef]
    [Google Scholar]
  23. Lazzarin, A., Clotet, B., Cooper, D. & 14 other authors ( 2003; ). Efficacy of enfuvirtide in patients infected with drug-resistant HIV-1 in Europe and Australia. N Engl J Med 348, 2186–2219.[CrossRef]
    [Google Scholar]
  24. Lifson, J. D., Feinberg, M. B., Reyes, G. R. & 7 other authors ( 1986; ). Induction of CD4-dependent cell fusion by the HTLV-III/LAV envelope glycoprotein. Nature 323, 725–728.[CrossRef]
    [Google Scholar]
  25. McKeating, J. A., Zhang, Y. J., Arnold, C., Frederiksson, R., Fenyo, E.-M. & Balfe, P. ( 1996; ). Chimeric viruses expressing primary envelope glycoproteins of human immunodeficiency virus type 1 show increased sensitivity to neutralization by human sera. Virology 220, 450–460.[CrossRef]
    [Google Scholar]
  26. Miedema, F., Meyaard, L., Koot, M. & 11 other authors ( 1994; ). Changing virus-host interactions in the course of HIV-1 infection. Immunol Rev 140, 35–72.[CrossRef]
    [Google Scholar]
  27. Montefiori, D. C., Pantaleo, G., Fink, L. M., Zhou, J. T., Zhou, J. Y., Bilska, M., Miralles, G. D. & Fauci, A. S. ( 1996; ). Neutralizing and infection-enhancing antibody responses to human immunodeficiency virus type 1 in long term nonprogressors. J Infect Dis 173, 60–67.[CrossRef]
    [Google Scholar]
  28. Muller, C., Kukel, S., Schneweis, K. E. & Bauer, R. ( 1994; ). Anti-lymphocyte antibodies in plasma of HIV-1-infected patients preferentially react with MHC class II-negative T cells and are linked to antibodies against gp41. Clin Exp Immunol 97, 367–372.
    [Google Scholar]
  29. Ngo-Giang-Huong, N., Candotti, D., Goubar, A. & 8 other authors ( 2001; ). HIV type 1-specific IgG2 antibodies: markers of helper T cell type 1 response and prognostic marker of long-term nonprogression. AIDS Res Hum Retroviruses 17, 1435–1446.[CrossRef]
    [Google Scholar]
  30. Pantaleo, G., Demarest, J. F., Vaccareza, M., Graziosi, C., Bansal, G. P., Koenig, S. & Fauci, A. S. ( 1995; ). Effect of anti-V3 antibodies on cell-free and cell-to-cell human immunodeficiency virus transmission. Eur J Immunol 25, 226–231.[CrossRef]
    [Google Scholar]
  31. Phillips, D. M. ( 1994; ). The role of cell-to-cell transmission in HIV infection. AIDS 8, 719–731.
    [Google Scholar]
  32. Pilgrim, A. K., Pantaleo, G., Cohen, O. J., Fink, L. M., Zhou, J. Y., Zhou, J. T., Bolognesi, D. P., Fauci, A. S. & Montefiori, D. C. ( 1997; ). Neutralizing antibody responses to human immunodeficiency virus type 1 in primary infection and long-term-nonprogressive infection. J Infect Dis 176, 924–932.[CrossRef]
    [Google Scholar]
  33. Poignard, P., Sabbe, R., Picchio, G. R., Wang, M., Gulizia, R. J., Katinger, H., Parren, P. W. H. I., Mosier, D. E. & Burton, D. R. ( 1999; ). Neutralizing antibodies have limited effects on the control of established HIV-1 infection in vivo. Immunity 10, 431–438.[CrossRef]
    [Google Scholar]
  34. Posner, M. R., Hideshima, T., Cannon, T., Mukherjee, M., Mayer, K. H. & Byrn, R. A. ( 1991; ). An IgG human monoclonal antibody that reacts with HIV-1/gp120, inhibits virus binding to cells, and neutralizes infection. J Immunol 146, 4325–4332.
    [Google Scholar]
  35. Robert-Guroff, M., Goedert, J. J., Naugle, C. J., Jenning, A. M., Blattner, W. A. & Gallo, R. C. ( 1988; ). Spectrum of HIV-1 neutralizing antibodies in a cohort of homosexual men: results of a 6 year prospective study. AIDS Res Hum Retroviruses 4, 343–350.[CrossRef]
    [Google Scholar]
  36. Sato, H., Orenstein, J., Dimitrov, D. & Martin, M. ( 1992; ). Cell-to-cell spread of HIV-1 occurs within minutes and may not involve the participation of virus particles. Virology 186, 712–724.[CrossRef]
    [Google Scholar]
  37. Sekigawa, I., Groopmen, J. E., Allan, J. D., Ikeuchi, K., Biberfield, G., Takatsuki, K. & Byrn, R. A. ( 1991; ). Characterization of autoantibodies to the CD4 molecule in human immunodeficiency virus infection. Clin Immunol Immunopathol 58, 145–153.[CrossRef]
    [Google Scholar]
  38. 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]
  39. Trkola, A., Ketas, T., Kewalramani, V. N., Endorf, F., Binley, J. M. & Katinger, H. ( 1998; ). Neutralization sensitivity of human immunodeficiency virus type 1 primary isolates to antibodies and CD4-based reagents is independent of coreceptor usage. J Virol 72, 1876–1885.
    [Google Scholar]
  40. WHO ( 2001; ). Monitoring the emergence of antiretroviral resistance. Report of a WHO consultation in collaboration with Instituto di Sanitá and the Internationl AIDS Society. WHO/CDS/CSR/DRS/2001.11. World Health Organization.
  41. Zwick, M. B., Wang, M., Poignard, P., Stiegler, G., Katinger, H., Burton, D. R. & Parren, P. W. ( 2001; ). Neutralization synergy of human immunodeficiency virus type 1 primary isolates by cocktails of broadly neutralizing antibodies. J Virol 75, 12198–12208.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.80635-0
Loading
/content/journal/jgv/10.1099/vir.0.80635-0
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