1887

Abstract

The CD4 T-cell reduction characteristic of human immunodeficiency virus type 1 (HIV-1) infection is thought to result, in addition to infected T-cell death, mainly from uninfected bystander T-cell apoptosis. Nevertheless, the immunological and virological mechanisms leading to T-cell death during HIV-1 infection are not yet fully understood. In the present study, we analysed the individual implication of the p38 mitogen-activated protein kinase (MAPK) isoforms (p38, p38, p38 and p38) during apoptosis induced by HIV-1, taking into account that HIV-1 replication is known to be blocked by p38 inhibitors. For this purpose, we used the SupT1 cell line, where death induced by HIV-1 mainly occurs by uninfected bystander cell apoptosis. A variety of SupT1-based cell lines were constructed constitutively expressing, under the control of cytomegalovirus promoter (PCMV), each dominant-negative (dn) p38 isoform and each wild-type p38 isoform as a control. An enhanced green fluorescent protein marker gene, under the control of the HIV-1 promoter, was inserted in all of them. These cell lines were infected with HIV-1 and analysed by flow cytometry. We found that survival in SupT1-based cell lines infected by HIV-1 was increased by the p38dn, p38dn and p38dn isoforms, but not by the p38dn isoform. HIV-1 replication was delayed most by p38dn and to a lesser extent by p38dn and p38dn. Moreover, these three isoforms, p38dn, p38dn and p38dn, reduced apoptosis induced by HIV-1. These results suggest that, in SupT1-based cell lines, p38, p38 and p38, but not p38, are implicated in both HIV-1 induced replication and apoptosis in infected and uninfected bystander cells.

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2008-07-01
2019-11-21
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References

  1. Abad, M. L., Verdura, T., Vela, A., Iglesias, M. J., Gutiérrez, D., Veiga, M., Aguilera, A. & Regueiro, B. J. ( 2004; ). Construction and characterization of a minimized version of the HIV-1 pNL4.3 plasmid and its application for pseudotyping HIV-1 vectors. Mol Biotechnol 28, 87–95.[CrossRef]
    [Google Scholar]
  2. Alcami, J., Lain de Lera, T., Folgueira, L., Pedraza, M. A., Jacque, J. M., Bachelerie, F., Noriega, A. R., Hay, R. T., Harrich, D. & other authors ( 1995; ). Absolute dependence on B responsive elements for initiation and Tat-mediated amplification of HIV transcription in blood CD4 T lymphocytes. EMBO J 14, 1552–1560.
    [Google Scholar]
  3. Algeciras-Schimnich, A., Vlahakis, S. R., Villasis-Keever, A., Gomez, T., Heppelmann, C. J., Bou, G. & Paya, C. V. ( 2002; ). CCR5 mediates Fas- and caspase-8 dependent apoptosis of both uninfected and HIV infected primary human CD4 T cells. AIDS 16, 1467–1478.[CrossRef]
    [Google Scholar]
  4. Asin, S., Bren, G. D., Carmona, E. M., Solan, N. J. & Paya, C. V. ( 2001; ). NF-κB cis-acting motifs of the human immunodeficiency virus (HIV) long terminal repeat regulate HIV transcription in human macrophages. J Virol 75, 11408–11416.[CrossRef]
    [Google Scholar]
  5. Azad, A. A. ( 2000; ). Could Nef and Vpr proteins contribute to disease progression by promoting depletion of bystander cells and prolonged survival of HIV-infected cells? Biochem Biophys Res Commun 267, 677–685.[CrossRef]
    [Google Scholar]
  6. Bartz, S. R. & Emerman, M. ( 1999; ). Human immunodeficiency virus type 1 Tat induces apoptosis and increases sensitivity to apoptotic signals by up-regulating FLICE/caspase-8. J Virol 73, 1956–1963.
    [Google Scholar]
  7. Brenner, C. & Kroemer, G. ( 2003; ). The mitochondriotoxic domain of Vpr determines HIV-1 virulence. J Clin Invest 111, 1455–1457.[CrossRef]
    [Google Scholar]
  8. Cao, J., Park, I., 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]
  9. Carbonari, M., Pesce, A. M., Cibati, M., Modica, A., Dell'Anna, L., D'Offici, G., Angelici, A., Uccini, A., Modesti, A. & other authors ( 1997; ). Death of bystander cells by a novel pathway involving early mitochondrial damage in human immunodeficiency virus-related lymphadenopathy. Blood 90, 209–216.
    [Google Scholar]
  10. Casella, C. R., Rapaport, E. L. & Finkel, T. H. ( 1999; ). Vpu increases susceptibility of human immunodeficiency virus type 1-infected cells to fas killing. J Virol 73, 92–100.
    [Google Scholar]
  11. Castedo, M. & Kroemer, G. ( 2002; ). The beauty of death. Trends Cell Biol 12, 446–447.[CrossRef]
    [Google Scholar]
  12. Castedo, M., Ferri, K. F., Blanco, J., Roumier, T., Larochette, N., Barretina, J., Amendola, A., Nardacci, R., Metivier, D. & other authors ( 2001; ). Human immunodeficiency virus 1 envelope glycoprotein complex-induced apoptosis involves mammalian target of rapamycin/FKBP12-rapamycin-associated protein-mediated p53 phosphorylation. J Exp Med 194, 1097–1110.[CrossRef]
    [Google Scholar]
  13. Castedo, M., Roumier, T., Blanco, J., Ferri, K. F., Barretina, L., Tintignac, L. A., Andreau, K., Perfettini, J. L., Amendola, A. & other authors ( 2002; ). Sequential involvement of Cdk1, mTOR, and p53 in apoptosis induced by the human immunodeficiency virus-1 envelope. EMBO J 21, 4070–4080.[CrossRef]
    [Google Scholar]
  14. Castedo, M., Perfettini, J. L., Andreau, K., Roumier, T., Piacentini, M. & Kroemer, G. ( 2003; ). Mitochondrial apoptosis induced by the HIV-1 envelope. Ann N Y Acad Sci 1010, 19–28.[CrossRef]
    [Google Scholar]
  15. Castedo, M., Perfettini, J. L., Piacentini, M. & Kroemer, G. ( 2005; ). p53–A pro apoptotic signal transducer involved in AIDS. Biochem Biophys Res Commun 331, 701–706.[CrossRef]
    [Google Scholar]
  16. Chowdhury, I. H., Wang, X. F., Landau, N. R., Robb, M. L., Polonis, V. R., Birx, D. L. & Kim, J. H. ( 2003; ). HIV-1 Vpr activates cell cycle inhibitor p21/Waf1/Cip1: a potential mechanism of G2/M cell cycle arrest. Virology 305, 371–377.[CrossRef]
    [Google Scholar]
  17. Cloyd, M. W., Chen, J. J. Y., Adeqboyega, P. & Wang, L. ( 2001; ). How does HIV cause depletion of CD4 lymphocytes? A mechanism involving virus signaling through its cellular receptors. Curr Mol Med 1, 545–550.[CrossRef]
    [Google Scholar]
  18. Cohen, P. S., Schmidtmayerova, H., Dennis, J., Dubrovsky, L., Sherry, B., Wang, H., Bukrinsky, M. & Tracey, K. J. ( 1997; ). The critical role of p38 MAP kinase in T cell HIV-1 replication. Mol Med 3, 339–346.
    [Google Scholar]
  19. Esser, M. T., Bess, J. W., Jr, Suryanarayana, K., Chertova, E., Marti, D., Carrington, M., Arthur, L. O. & Lifson, J. D. ( 2001; ). Partial activation and induction of apoptosis in CD4+ and CD8+ T lymphocytes by conformationally authentic noninfectious human immunodeficiency virus type 1. J Virol 75, 1152–1164.[CrossRef]
    [Google Scholar]
  20. Ferri, K. F., Jacotot, E., Blanco, J., Esté, J. A., Zamzami, A., Susin, S. A., Brothers, G., Reed, J. C., Penninger, J. M. & other authors ( 2000; ). Apoptosis control in syncytia induced by the HIV-1-envelope glycoprotein complex. Role of mitochondria and caspases. J Exp Med 192, 1081–1092.[CrossRef]
    [Google Scholar]
  21. Finkel, T. H., Tudor-Williams, G., Banda, N. K., Cotton, M. F., Curiel, T., Monks, C., Baba, T. W., Ruprecht, R. M. & Kupfer, A. ( 1995; ). Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes. Nat Med 1, 129–134.[CrossRef]
    [Google Scholar]
  22. Gandhi, R. T., Chen, B. K., Straus, S. E., Dale, J. K., Lenardo, M. J. & Baltimore, D. ( 1998; ). HIV-1 directly kills CD4+ T cells by a Fas-independent mechanism. J Exp Med 187, 1113–1122.[CrossRef]
    [Google Scholar]
  23. Genini, D., Sheeter, D., Rought, S., Zaunders, J. J., Susin, S. A., Kroemer, G., Richman, D. D., Carson, D. A., Corbeil, J. & other authors ( 2001; ). HIV induces lymphocyte apoptosis by a p53-initiated, mitochondrial-mediated mechanism. FASEB J 15, 5–6.
    [Google Scholar]
  24. Grivel, J. C., Malkevitch, N. & Margolis, L. ( 2000; ). Human immunodeficiency virus type 1 induces apoptosis in CD4+ but not in CD8+ T cells in ex vivo-infected human lymphoid tissue. J Virol 74, 8077–8084.[CrossRef]
    [Google Scholar]
  25. Herbein, G., Van Lint, C., Lovett, J. L. & Verdin, E. ( 1998a; ). Distinct mechanisms trigger apoptosis in human immunodeficiency virus type 1-infected and in uninfected bystander T lymphocytes. J Virol 72, 660–670.
    [Google Scholar]
  26. Herbein, G., Mahlknecht, U., Batliwalla, F., Gregersen, P., Pappas, T., Butler, J., O'Brien, W. A. & Verdin, E. ( 1998b; ). Apoptosis of CD8+ T cells is mediated by macrophages through interaction of HIV gp120 with chemokine receptor CXCR4. Nature 395, 189–194.[CrossRef]
    [Google Scholar]
  27. Holm, G. H., Zhang, C., Gorry, P. R., Peden, K., Schols, D., De Clercq, E. & Gabuzda, D. ( 2004; ). Apoptosis of bystander T cells induced by human immunodeficiency virus type 1 with increased envelope/receptor affinity and coreceptor binding site exposure. J Virol 78, 4541–4551.[CrossRef]
    [Google Scholar]
  28. Jacotot, E., Ferri, K. F., El Hamel, C., Brenner, C., Druillennec, S., Hoebeke, J., Rustin, P., Metivier, D., Lenoir, C. & other authors ( 2001; ). Control of mitochondrial membrane permeabilization by adenine nucleotide translocator interacting with HIV-1 Vpr and Bcl-2. J Exp Med 193, 509–519.[CrossRef]
    [Google Scholar]
  29. Katsikis, P. D., Wunderlich, E. S., Smith, C. A., Herzenberg, L. A. & Herzenberg, L. A. ( 1995; ). Fas antigen stimulation induces marked apoptosis of T lymphocytes in human immunodeficiency virus-infected individuals. J Exp Med 181, 2029–2036.[CrossRef]
    [Google Scholar]
  30. Kumar, S., Orsini, M. J., Lee, J. C., McDonnell, P. C., Debouck, C. & Young, P. R. ( 1996; ). Activation of the HIV-1 long terminal repeat by cytokines and environmental stress requires an active CSBP/p38 MAP kinase. J Biol Chem 271, 30864–30869.[CrossRef]
    [Google Scholar]
  31. LaBonte, J. A., Madani, N. & Sodroski, J. ( 2003; ). Cytolysis by CCR5-using human immunodeficiency virus type 1 envelope glycoproteins is dependent on membrane fusion and can be inhibited by high levels of CD4 expression. J Virol 77, 6645–6659.[CrossRef]
    [Google Scholar]
  32. Lenardo, M. J., Angleman, S. B., Bounkeua, V., Dimas, J., Duvall, M. G., Graubard, M. S., Hornung, F., Selkirk, M. C., Speirs, C. K. & other authors ( 2002; ). Cytopathic killing of peripheral blood CD4+ T lymphocytes by human immunodeficiency virus type 1 appears necrotic rather than apoptotic and does not require env. J Virol 76, 5082–5093.[CrossRef]
    [Google Scholar]
  33. Lum, J. J., Cohen, O. J., Nie, Z., Weaver, J. G., Gomez, T. S., Yao, X. J., Lynch, D., Pilon, A. A., Hawley, N. & other authors ( 2003; ). Vpr R77Q is associated with long18 term nonprogressive HIV infection and impaired induction of apoptosis. J Clin Invest 111, 1547–1554.[CrossRef]
    [Google Scholar]
  34. McCune, J. M. ( 2001; ). The dynamics of CD4+ T-cell depletion in HIV disease. Nature 410, 974–979.[CrossRef]
    [Google Scholar]
  35. Mizumura, K., Takeda, K., Hashimoto, S., Oiré, T. & Ichijo, H. ( 2006; ). Identification of Op18/stathmin as a potential target of ASK1-p38 MAP kinase cascade. J Cell Physiol 206, 363–370.[CrossRef]
    [Google Scholar]
  36. Muthumani, K., Wadsworth, S. A., Dayes, N. S., Hwang, D. S., Choo, A. Y., Abeysinghe, H. R., Siekierka, J. J. & Weiner, D. B. ( 2004; ). Suppression of HIV-1 viral replication and cellular pathogenesis by a novel p38/JNK kinase inhibitor. AIDS 18, 739–748.[CrossRef]
    [Google Scholar]
  37. Muthumani, K., Choo, A. Y., Hwang, D. S., Premkumar, A., Dayes, N. S., Harris, C., Green, D. R., Wadsworth, S. A., Siekierka, J. J. & other authors ( 2005; ). HIV-1 Nef induced FasL induction and bystander killing requires p38 MAPK activation. Blood 106, 2059–2068.[CrossRef]
    [Google Scholar]
  38. Nie, Z., Phenix, B. N., Lum, J. J., Alam, A., Lynch, D. H., Beckett, B., Krammer, P. H., Sekaly, R. P. & Badley, A. D. ( 2002; ). HIV-1 protease processes procaspase 8 to cause mitochondrial release of cytochrome c, caspase cleavage and nuclear fragmentation. Cell Death Differ 9, 1172–1184.[CrossRef]
    [Google Scholar]
  39. Parker, C. G., Hunt, J., Diener, K., McGinley, M., Soriano, B., Keesler, G. A., Bray, J., Yao, Z. & other authors ( 1998; ). Identification of stathmin as a novel substrate for p38 delta. Biochem Biophys Res Commun 249, 791–796.[CrossRef]
    [Google Scholar]
  40. Perfettini, J.-L. & Kroemer, G. ( 2005; ). p38 MAP kinase in HIV-1 infection: the enemy within. Blood 106, 1899–1900.[CrossRef]
    [Google Scholar]
  41. Perfettini, J. L., Roumier, T., Castedo, M., Larochette, N., Boya, P., Raynal, B., Lazar, V., Ciccosanti, F., Nardacci, R. & other authors ( 2004; ). NF-κB and p53 are the dominant apoptosis-inducing transcription factors elicited by the HIV-1 envelope. J Exp Med 199, 629–640.[CrossRef]
    [Google Scholar]
  42. Perfettini, J. L., Castedo, M., Nardacci, R., Ciccosanti, F., Boya, P., Roumier, T., Larochette, N., Piacentini, M. & Kroemer, G. ( 2005; ). Essential role of p53 phosphorylation by p38 MAPK in apoptosis induction by the HIV-1 envelope. J Exp Med 201, 279–289.[CrossRef]
    [Google Scholar]
  43. Pramanik, R., Qi, X., Borowicz, S., Choubey, D., Schultz, R. M., Han, J. & Chen, G. ( 2003; ). p38 isoforms have opposite effects on AP-1-dependent transcription through regulation of c-Jun. J Biol Chem 278, 4831–4839.[CrossRef]
    [Google Scholar]
  44. Roumier, T., Vieira, H. L., Castedo, M., Ferri, K. F., Boya, P., Andreau, K., Druillennec, S., Joza, N. & other authors ( 2002; ). The C-terminal moiety of HIV-1 Vpr induces cell death via a caspase-independent mitochondrial pathway. Cell Death Differ 9, 1212–1219.[CrossRef]
    [Google Scholar]
  45. Sambrook, J., Fritsch, E. F. & Maniatis, T. ( 1989; ). &SetFont Bold="0";Molecular Cloning: a Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.
  46. Shapiro, L., Heidenreich, K. A., Meintzer, M. K. & Dinarello, C. A. ( 1998; ). Role of p38 mitogen-activated protein kinase in HIV type 1 production in vitro. Proc Natl Acad Sci U S A 95, 7422–7426.[CrossRef]
    [Google Scholar]
  47. Seidman, C. E., Struhl, K., Sheen, J. & Jessen, T. ( 1994; ). Introduction of plasmid DNA into cells. In Current Protocols in Molecular Biology, vol. 1, pp. 1.8.1–1.8.6. Edited by F. M. Ausubel, R. Brent, R. E. Kingston, D. D. Moore, J. G. Seidman, J. A. Smith & K. Struhl. New York, NY: Greene Publishing Associates and J. Wiley & Sons.
  48. Silvestris, F., Camarda, G., Del Prete, A., Tucci, M. & Dammacco, F. ( 1999; ). Nef protein induces differential effects in CD8+ cells from HIV-1-infected patients. Eur J Clin Invest 29, 980–991.[CrossRef]
    [Google Scholar]
  49. Vlahakis, S. R., Algeciras-Schimnich, A., Bou, G., Heppelmann, C. J., Villasis-Keever, A., Collman, R. G. & Paya, C. V. ( 2001; ). Chemokine-receptor activation by env determines the mechanism of death in HIV-infected and uninfected T lymphocytes. J Clin Invest 107, 207–215.[CrossRef]
    [Google Scholar]
  50. Wu, B. Y., Woffendin, C., MacLachlan, I. & Nabel, G. J. ( 1997; ). Distinct domains of I B-inhibit human immunodeficiency virus type 1 replication through NF-κB and Rev. J Virol 71, 3161–3167.
    [Google Scholar]
  51. Yang, Y., Tikhonov, I., Ruckwardt, T. J., Djavani, M., Zapata, J. C., Pauza, C. D. & Salvato, M. S. ( 2003; ). Monocytes treated with human immunodeficiency virus Tat kill uninfected CD4+ cells by a tumor necrosis factor-related apoptosis-induced ligand mediated mechanism. J Virol 77, 6700–6708.[CrossRef]
    [Google Scholar]
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