Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1997 Dec;71(12):9753–9763. doi: 10.1128/jvi.71.12.9753-9763.1997

A major human immunodeficiency virus type 1-initiated killing pathway distinct from apoptosis.

V Kolesnitchenko 1, L King 1, A Riva 1, Y Tani 1, S J Korsmeyer 1, D I Cohen 1
PMCID: PMC230285  PMID: 9371641

Abstract

We have investigated the relative contribution of apoptosis or programmed cell death (PCD) to cell killing during acute infection with T-cell-tropic, cytopathic human immunodeficiency virus type 1 (HIV-1), by employing diverse strategies to inhibit PCD or to detect its common end-stage sequelae. When Bcl-2-transfected cell lines were infected with HIV-1, their viability was only slightly higher than that of control infections. Although the adenovirus E1B 19-kDa protein has been reported to be a stronger competitor of apoptosis than Bcl-2, it did not inhibit HIV-mediated cell death better than Bcl-2 protein. Competition for Fas ligand or inactivation of the Fas pathway secondary to intracellular mutation (MOLT-4 T cells) also had modest effects on overall cell death during acute HIV infection. In contrast to these observations with HIV infection or with HIV envelope-initiated cell death, Tat-expressing cell lines were much more susceptible (200% enhancement) to Fas-induced apoptosis than controls and Bcl-2 overexpression strongly (75%) inhibited this apoptotic T-cell death. PCD associated with FasR ligation resulted in the cleavage of common interleukin-1beta-converting enzyme (ICE)-protease targets, poly(ADP-ribose) polymerase (PARP) and pro-ICE, whereas cleaved products were not readily detected during HIV infection of peripheral blood mononuclear cells or T-cell lines even during periods of extensive cell death. These results indicate that one important form of HIV-mediated cell killing proceeds by a pathway that lacks the characteristics of T-cell apoptosis. Our observations support the conclusion that at least two HIV genes (env and tat) can kill T cells by distinct pathways and that an envelope-initiated process of T-cell death can be discriminated from apoptosis by many of the properties most closely associated with apoptotic cell death.

Full Text

The Full Text of this article is available as a PDF (873.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alderson M. R., Tough T. W., Davis-Smith T., Braddy S., Falk B., Schooley K. A., Goodwin R. G., Smith C. A., Ramsdell F., Lynch D. H. Fas ligand mediates activation-induced cell death in human T lymphocytes. J Exp Med. 1995 Jan 1;181(1):71–77. doi: 10.1084/jem.181.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ameisen J. C., Capron A. Cell dysfunction and depletion in AIDS: the programmed cell death hypothesis. Immunol Today. 1991 Apr;12(4):102–105. doi: 10.1016/0167-5699(91)90092-8. [DOI] [PubMed] [Google Scholar]
  3. Antoni B. A., Sabbatini P., Rabson A. B., White E. Inhibition of apoptosis in human immunodeficiency virus-infected cells enhances virus production and facilitates persistent infection. J Virol. 1995 Apr;69(4):2384–2392. doi: 10.1128/jvi.69.4.2384-2392.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Badley A. D., McElhinny J. A., Leibson P. J., Lynch D. H., Alderson M. R., Paya C. V. Upregulation of Fas ligand expression by human immunodeficiency virus in human macrophages mediates apoptosis of uninfected T lymphocytes. J Virol. 1996 Jan;70(1):199–206. doi: 10.1128/jvi.70.1.199-206.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bakhshi A., Jensen J. P., Goldman P., Wright J. J., McBride O. W., Epstein A. L., Korsmeyer S. J. Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around JH on chromosome 14 and near a transcriptional unit on 18. Cell. 1985 Jul;41(3):899–906. doi: 10.1016/s0092-8674(85)80070-2. [DOI] [PubMed] [Google Scholar]
  6. Banda N. K., Bernier J., Kurahara D. K., Kurrle R., Haigwood N., Sekaly R. P., Finkel T. H. Crosslinking CD4 by human immunodeficiency virus gp120 primes T cells for activation-induced apoptosis. J Exp Med. 1992 Oct 1;176(4):1099–1106. doi: 10.1084/jem.176.4.1099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Boldin M. P., Goncharov T. M., Goltsev Y. V., Wallach D. Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death. Cell. 1996 Jun 14;85(6):803–815. doi: 10.1016/s0092-8674(00)81265-9. [DOI] [PubMed] [Google Scholar]
  8. Cao J., Park I. W., Cooper A., Sodroski J. Molecular determinants of acute single-cell lysis by human immunodeficiency virus type 1. J Virol. 1996 Mar;70(3):1340–1354. doi: 10.1128/jvi.70.3.1340-1354.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Clarke P. G. Developmental cell death: morphological diversity and multiple mechanisms. Anat Embryol (Berl) 1990;181(3):195–213. doi: 10.1007/BF00174615. [DOI] [PubMed] [Google Scholar]
  10. Clerici M., Shearer G. M. A TH1-->TH2 switch is a critical step in the etiology of HIV infection. Immunol Today. 1993 Mar;14(3):107–111. doi: 10.1016/0167-5699(93)90208-3. [DOI] [PubMed] [Google Scholar]
  11. Cohen J. J. Programmed cell death in the immune system. Adv Immunol. 1991;50:55–85. doi: 10.1016/s0065-2776(08)60822-6. [DOI] [PubMed] [Google Scholar]
  12. Connor R. I., Ho D. D. Human immunodeficiency virus type 1 variants with increased replicative capacity develop during the asymptomatic stage before disease progression. J Virol. 1994 Jul;68(7):4400–4408. doi: 10.1128/jvi.68.7.4400-4408.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Connor R. I., Mohri H., Cao Y., Ho D. D. 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. 1993 Apr;67(4):1772–1777. doi: 10.1128/jvi.67.4.1772-1777.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Craig R. W. The bcl-2 gene family. Semin Cancer Biol. 1995 Feb;6(1):35–43. doi: 10.1006/scbi.1995.0005. [DOI] [PubMed] [Google Scholar]
  15. Dhein J., Walczak H., Bäumler C., Debatin K. M., Krammer P. H. Autocrine T-cell suicide mediated by APO-1/(Fas/CD95) Nature. 1995 Feb 2;373(6513):438–441. doi: 10.1038/373438a0. [DOI] [PubMed] [Google Scholar]
  16. Diamond D. C., Sleckman B. P., Gregory T., Lasky L. A., Greenstein J. L., Burakoff S. J. Inhibition of CD4+ T cell function by the HIV envelope protein, gp120. J Immunol. 1988 Dec 1;141(11):3715–3717. [PubMed] [Google Scholar]
  17. Draetta G., Beach D. Activation of cdc2 protein kinase during mitosis in human cells: cell cycle-dependent phosphorylation and subunit rearrangement. Cell. 1988 Jul 1;54(1):17–26. doi: 10.1016/0092-8674(88)90175-4. [DOI] [PubMed] [Google Scholar]
  18. Estaquier J., Idziorek T., Zou W., Emilie D., Farber C. M., Bourez J. M., Ameisen J. C. T helper type 1/T helper type 2 cytokines and T cell death: preventive effect of interleukin 12 on activation-induced and CD95 (FAS/APO-1)-mediated apoptosis of CD4+ T cells from human immunodeficiency virus-infected persons. J Exp Med. 1995 Dec 1;182(6):1759–1767. doi: 10.1084/jem.182.6.1759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Estaquier J., Tanaka M., Suda T., Nagata S., Golstein P., Ameisen J. C. Fas-mediated apoptosis of CD4+ and CD8+ T cells from human immunodeficiency virus-infected persons: differential in vitro preventive effect of cytokines and protease antagonists. Blood. 1996 Jun 15;87(12):4959–4966. [PubMed] [Google Scholar]
  20. Fauci A. S. Multifactorial nature of human immunodeficiency virus disease: implications for therapy. Science. 1993 Nov 12;262(5136):1011–1018. doi: 10.1126/science.8235617. [DOI] [PubMed] [Google Scholar]
  21. Fauci A. S. The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science. 1988 Feb 5;239(4840):617–622. doi: 10.1126/science.3277274. [DOI] [PubMed] [Google Scholar]
  22. Goldman F., Jensen W. A., Johnson G. L., Heasley L., Cambier J. C. gp120 ligation of CD4 induces p56lck activation and TCR desensitization independent of TCR tyrosine phosphorylation. J Immunol. 1994 Oct 1;153(7):2905–2917. [PubMed] [Google Scholar]
  23. Groux H., Torpier G., Monté D., Mouton Y., Capron A., Ameisen J. C. Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals. J Exp Med. 1992 Feb 1;175(2):331–340. doi: 10.1084/jem.175.2.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hashimoto S., Ishii A., Yonehara S. The E1b oncogene of adenovirus confers cellular resistance to cytotoxicity of tumor necrosis factor and monoclonal anti-Fas antibody. Int Immunol. 1991 Apr;3(4):343–351. doi: 10.1093/intimm/3.4.343. [DOI] [PubMed] [Google Scholar]
  25. He J., Choe S., Walker R., Di Marzio P., Morgan D. O., Landau N. R. Human immunodeficiency virus type 1 viral protein R (Vpr) arrests cells in the G2 phase of the cell cycle by inhibiting p34cdc2 activity. J Virol. 1995 Nov;69(11):6705–6711. doi: 10.1128/jvi.69.11.6705-6711.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hengartner M. O., Horvitz H. R. C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2. Cell. 1994 Feb 25;76(4):665–676. doi: 10.1016/0092-8674(94)90506-1. [DOI] [PubMed] [Google Scholar]
  27. Henkart P. A. ICE family proteases: mediators of all apoptotic cell death? Immunity. 1996 Mar;4(3):195–201. doi: 10.1016/s1074-7613(00)80428-8. [DOI] [PubMed] [Google Scholar]
  28. Hivroz C., Mazerolles F., Soula M., Fagard R., Graton S., Meloche S., Sekaly R. P., Fischer A. Human immunodeficiency virus gp120 and derived peptides activate protein tyrosine kinase p56lck in human CD4 T lymphocytes. Eur J Immunol. 1993 Mar;23(3):600–607. doi: 10.1002/eji.1830230303. [DOI] [PubMed] [Google Scholar]
  29. Ho D. D., Neumann A. U., Perelson A. S., Chen W., Leonard J. M., Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. 1995 Jan 12;373(6510):123–126. doi: 10.1038/373123a0. [DOI] [PubMed] [Google Scholar]
  30. Hockenbery D., Nuñez G., Milliman C., Schreiber R. D., Korsmeyer S. J. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature. 1990 Nov 22;348(6299):334–336. doi: 10.1038/348334a0. [DOI] [PubMed] [Google Scholar]
  31. Häcker G., Vaux D. L. Apoptosis. A sticky business. Curr Biol. 1995 Jun 1;5(6):622–624. doi: 10.1016/s0960-9822(95)00126-6. [DOI] [PubMed] [Google Scholar]
  32. Imberti L., Sottini A., Bettinardi A., Puoti M., Primi D. Selective depletion in HIV infection of T cells that bear specific T cell receptor V beta sequences. Science. 1991 Nov 8;254(5033):860–862. doi: 10.1126/science.1948066. [DOI] [PubMed] [Google Scholar]
  33. Jacobson M. D., Weil M., Raff M. C. Programmed cell death in animal development. Cell. 1997 Feb 7;88(3):347–354. doi: 10.1016/s0092-8674(00)81873-5. [DOI] [PubMed] [Google Scholar]
  34. Jowett J. B., Planelles V., Poon B., Shah N. P., Chen M. L., Chen I. S. The human immunodeficiency virus type 1 vpr gene arrests infected T cells in the G2 + M phase of the cell cycle. J Virol. 1995 Oct;69(10):6304–6313. doi: 10.1128/jvi.69.10.6304-6313.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Katsikis P. D., Wunderlich E. S., Smith C. A., Herzenberg L. A., Herzenberg L. A. Fas antigen stimulation induces marked apoptosis of T lymphocytes in human immunodeficiency virus-infected individuals. J Exp Med. 1995 Jun 1;181(6):2029–2036. doi: 10.1084/jem.181.6.2029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Kolesnitchenko V., Wahl L. M., Tian H., Sunila I., Tani Y., Hartmann D. P., Cossman J., Raffeld M., Orenstein J., Samelson L. E. Human immunodeficiency virus 1 envelope-initiated G2-phase programmed cell death. Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11889–11893. doi: 10.1073/pnas.92.25.11889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Laurent-Crawford A. G., Coccia E., Krust B., Hovanessian A. G. Membrane-expressed HIV envelope glycoprotein heterodimer is a powerful inducer of cell death in uninfected CD4+ target cells. Res Virol. 1995 Jan-Feb;146(1):5–17. doi: 10.1016/0923-2516(96)80585-1. [DOI] [PubMed] [Google Scholar]
  38. Laurent-Crawford A. G., Krust B., Rivière Y., Desgranges C., Muller S., Kieny M. P., Dauguet C., Hovanessian A. G. Membrane expression of HIV envelope glycoproteins triggers apoptosis in CD4 cells. AIDS Res Hum Retroviruses. 1993 Aug;9(8):761–773. doi: 10.1089/aid.1993.9.761. [DOI] [PubMed] [Google Scholar]
  39. Li C. J., Friedman D. J., Wang C., Metelev V., Pardee A. B. Induction of apoptosis in uninfected lymphocytes by HIV-1 Tat protein. Science. 1995 Apr 21;268(5209):429–431. doi: 10.1126/science.7716549. [DOI] [PubMed] [Google Scholar]
  40. McCloskey T. W., Ott M., Tribble E., Khan S. A., Teichberg S., Paul M. O., Pahwa S., Verdin E., Chirmule N. Dual role of HIV Tat in regulation of apoptosis in T cells. J Immunol. 1997 Jan 15;158(2):1014–1019. [PubMed] [Google Scholar]
  41. McGowan C. H., Russell P. Human Wee1 kinase inhibits cell division by phosphorylating p34cdc2 exclusively on Tyr15. EMBO J. 1993 Jan;12(1):75–85. doi: 10.1002/j.1460-2075.1993.tb05633.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Merćep M., Noguchi P. D., Ashwell J. D. The cell cycle block and lysis of an activated T cell hybridoma are distinct processes with different Ca2+ requirements and sensitivity to cyclosporine A. J Immunol. 1989 Jun 1;142(11):4085–4092. [PubMed] [Google Scholar]
  43. Meyaard L., Otto S. A., Jonker R. R., Mijnster M. J., Keet R. P., Miedema F. Programmed death of T cells in HIV-1 infection. Science. 1992 Jul 10;257(5067):217–219. doi: 10.1126/science.1352911. [DOI] [PubMed] [Google Scholar]
  44. Meyaard L., Otto S. A., Keet I. P., Roos M. T., Miedema F. Programmed death of T cells in human immunodeficiency virus infection. No correlation with progression to disease. J Clin Invest. 1994 Mar;93(3):982–988. doi: 10.1172/JCI117105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Mittler R. S., Hoffmann M. K. Synergism between HIV gp120 and gp120-specific antibody in blocking human T cell activation. Science. 1989 Sep 22;245(4924):1380–1382. doi: 10.1126/science.2571187. [DOI] [PubMed] [Google Scholar]
  46. Muzio M., Chinnaiyan A. M., Kischkel F. C., O'Rourke K., Shevchenko A., Ni J., Scaffidi C., Bretz J. D., Zhang M., Gentz R. FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death--inducing signaling complex. Cell. 1996 Jun 14;85(6):817–827. doi: 10.1016/s0092-8674(00)81266-0. [DOI] [PubMed] [Google Scholar]
  47. Müller W. E., Schröder H. C., Ushijima H., Dapper J., Bormann J. gp120 of HIV-1 induces apoptosis in rat cortical cell cultures: prevention by memantine. Eur J Pharmacol. 1992 Jul 1;226(3):209–214. doi: 10.1016/0922-4106(92)90063-2. [DOI] [PubMed] [Google Scholar]
  48. Na S., Chuang T. H., Cunningham A., Turi T. G., Hanke J. H., Bokoch G. M., Danley D. E. D4-GDI, a substrate of CPP32, is proteolyzed during Fas-induced apoptosis. J Biol Chem. 1996 May 10;271(19):11209–11213. doi: 10.1074/jbc.271.19.11209. [DOI] [PubMed] [Google Scholar]
  49. Nagata S., Golstein P. The Fas death factor. Science. 1995 Mar 10;267(5203):1449–1456. doi: 10.1126/science.7533326. [DOI] [PubMed] [Google Scholar]
  50. Park I. W., Kondo E., Bergeron L., Park J., Sodroski J. Effects of human immunodeficiency virus type 1 infection on programmed cell death in the presence or absence of Bcl-2. J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Aug 1;12(4):321–328. doi: 10.1097/00042560-199608010-00001. [DOI] [PubMed] [Google Scholar]
  51. Purvis S. F., Jacobberger J. W., Sramkoski R. M., Patki A. H., Lederman M. M. HIV type 1 Tat protein induces apoptosis and death in Jurkat cells. AIDS Res Hum Retroviruses. 1995 Apr;11(4):443–450. doi: 10.1089/aid.1995.11.443. [DOI] [PubMed] [Google Scholar]
  52. Raff M. C. Social controls on cell survival and cell death. Nature. 1992 Apr 2;356(6368):397–400. doi: 10.1038/356397a0. [DOI] [PubMed] [Google Scholar]
  53. Re F., Braaten D., Franke E. K., Luban J. Human immunodeficiency virus type 1 Vpr arrests the cell cycle in G2 by inhibiting the activation of p34cdc2-cyclin B. J Virol. 1995 Nov;69(11):6859–6864. doi: 10.1128/jvi.69.11.6859-6864.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Rosenberg Z. F., Fauci A. S. The immunopathogenesis of HIV infection. Adv Immunol. 1989;47:377–431. doi: 10.1016/s0065-2776(08)60665-3. [DOI] [PubMed] [Google Scholar]
  55. Sadaie M. R., Hager G. L. Induction of developmentally programmed cell death and activation of HIV by sodium butyrate. Virology. 1994 Jul;202(1):513–518. doi: 10.1006/viro.1994.1372. [DOI] [PubMed] [Google Scholar]
  56. Sandstrom P. A., Pardi D., Goldsmith C. S., Chengying D., Diamond A. M., Folks T. M. bc1-2 expression facilitates human immunodeficiency virus type-1 mediated cytopathic effects during acute spreading infections. J Virol. 1996 Jul;70(7):4617–4622. doi: 10.1128/jvi.70.7.4617-4622.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Sarin A., Clerici M., Blatt S. P., Hendrix C. W., Shearer G. M., Henkart P. A. Inhibition of activation-induced programmed cell death and restoration of defective immune responses of HIV+ donors by cysteine protease inhibitors. J Immunol. 1994 Jul 15;153(2):862–872. [PubMed] [Google Scholar]
  58. Schnittman S. M., Lane H. C., Greenhouse J., Justement J. S., Baseler M., Fauci A. S. Preferential infection of CD4+ memory T cells by human immunodeficiency virus type 1: evidence for a role in the selective T-cell functional defects observed in infected individuals. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6058–6062. doi: 10.1073/pnas.87.16.6058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Sentman C. L., Shutter J. R., Hockenbery D., Kanagawa O., Korsmeyer S. J. bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes. Cell. 1991 Nov 29;67(5):879–888. doi: 10.1016/0092-8674(91)90361-2. [DOI] [PubMed] [Google Scholar]
  60. Sodroski J., Goh W. C., Rosen C., Campbell K., Haseltine W. A. Role of the HTLV-III/LAV envelope in syncytium formation and cytopathicity. 1986 Jul 31-Aug 6Nature. 322(6078):470–474. doi: 10.1038/322470a0. [DOI] [PubMed] [Google Scholar]
  61. Stewart S. A., Poon B., Jowett J. B., Chen I. S. Human immunodeficiency virus type 1 Vpr induces apoptosis following cell cycle arrest. J Virol. 1997 Jul;71(7):5579–5592. doi: 10.1128/jvi.71.7.5579-5592.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Strack P. R., Frey M. W., Rizzo C. J., Cordova B., George H. J., Meade R., Ho S. P., Corman J., Tritch R., Korant B. D. Apoptosis mediated by HIV protease is preceded by cleavage of Bcl-2. Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9571–9576. doi: 10.1073/pnas.93.18.9571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Strasser A., Harris A. W., Huang D. C., Krammer P. H., Cory S. Bcl-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis. EMBO J. 1995 Dec 15;14(24):6136–6147. doi: 10.1002/j.1460-2075.1995.tb00304.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Su X., Zhou T., Wang Z., Yang P., Jope R. S., Mountz J. D. Defective expression of hematopoietic cell protein tyrosine phosphatase (HCP) in lymphoid cells blocks Fas-mediated apoptosis. Immunity. 1995 Apr;2(4):353–362. doi: 10.1016/1074-7613(95)90143-4. [DOI] [PubMed] [Google Scholar]
  65. Tani Y., Tian H., Lane H. C., Cohen D. I. Normal T cell receptor-mediated signaling in T cell lines stably expressing HIV-1 envelope glycoproteins. J Immunol. 1993 Dec 15;151(12):7337–7348. [PubMed] [Google Scholar]
  66. Terai C., Kornbluth R. S., Pauza C. D., Richman D. D., Carson D. A. Apoptosis as a mechanism of cell death in cultured T lymphoblasts acutely infected with HIV-1. J Clin Invest. 1991 May;87(5):1710–1715. doi: 10.1172/JCI115188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Tersmette M., Gruters R. A., de Wolf F., de Goede R. E., Lange J. M., Schellekens P. T., Goudsmit J., Huisman H. G., Miedema F. Evidence for a role of virulent human immunodeficiency virus (HIV) variants in the pathogenesis of acquired immunodeficiency syndrome: studies on sequential HIV isolates. J Virol. 1989 May;63(5):2118–2125. doi: 10.1128/jvi.63.5.2118-2125.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Tersmette M., de Goede R. E., Al B. J., Winkel I. N., Gruters R. A., Cuypers H. T., Huisman H. G., Miedema F. Differential syncytium-inducing capacity of human immunodeficiency virus isolates: frequent detection of syncytium-inducing isolates in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. J Virol. 1988 Jun;62(6):2026–2032. doi: 10.1128/jvi.62.6.2026-2032.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Trauth B. C., Klas C., Peters A. M., Matzku S., Möller P., Falk W., Debatin K. M., Krammer P. H. Monoclonal antibody-mediated tumor regression by induction of apoptosis. Science. 1989 Jul 21;245(4915):301–305. doi: 10.1126/science.2787530. [DOI] [PubMed] [Google Scholar]
  70. Tsujimoto Y., Croce C. M. Analysis of the structure, transcripts, and protein products of bcl-2, the gene involved in human follicular lymphoma. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5214–5218. doi: 10.1073/pnas.83.14.5214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Tsujimoto Y. Stress-resistance conferred by high level of bcl-2 alpha protein in human B lymphoblastoid cell. Oncogene. 1989 Nov;4(11):1331–1336. [PubMed] [Google Scholar]
  72. Wei X., Ghosh S. K., Taylor M. E., Johnson V. A., Emini E. A., Deutsch P., Lifson J. D., Bonhoeffer S., Nowak M. A., Hahn B. H. Viral dynamics in human immunodeficiency virus type 1 infection. Nature. 1995 Jan 12;373(6510):117–122. doi: 10.1038/373117a0. [DOI] [PubMed] [Google Scholar]
  73. Westendorp M. O., Frank R., Ochsenbauer C., Stricker K., Dhein J., Walczak H., Debatin K. M., Krammer P. H. Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120. Nature. 1995 Jun 8;375(6531):497–500. doi: 10.1038/375497a0. [DOI] [PubMed] [Google Scholar]
  74. White E., Sabbatini P., Debbas M., Wold W. S., Kusher D. I., Gooding L. R. The 19-kilodalton adenovirus E1B transforming protein inhibits programmed cell death and prevents cytolysis by tumor necrosis factor alpha. Mol Cell Biol. 1992 Jun;12(6):2570–2580. doi: 10.1128/mcb.12.6.2570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Wyllie A. H., Arends M. J., Morris R. G., Walker S. W., Evan G. The apoptosis endonuclease and its regulation. Semin Immunol. 1992 Dec;4(6):389–397. [PubMed] [Google Scholar]
  76. Wyllie A. H., Morris R. G., Smith A. L., Dunlop D. Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macromolecular synthesis. J Pathol. 1984 Jan;142(1):67–77. doi: 10.1002/path.1711420112. [DOI] [PubMed] [Google Scholar]
  77. Xiang J., Chao D. T., Korsmeyer S. J. BAX-induced cell death may not require interleukin 1 beta-converting enzyme-like proteases. Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14559–14563. doi: 10.1073/pnas.93.25.14559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Yang E., Korsmeyer S. J. Molecular thanatopsis: a discourse on the BCL2 family and cell death. Blood. 1996 Jul 15;88(2):386–401. [PubMed] [Google Scholar]
  79. Yonehara S., Ishii A., Yonehara M. A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor. J Exp Med. 1989 May 1;169(5):1747–1756. doi: 10.1084/jem.169.5.1747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Yonehara S., Nishimura Y., Kishil S., Yonehara M., Takazawa K., Tamatani T., Ishii A. Involvement of apoptosis antigen Fas in clonal deletion of human thymocytes. Int Immunol. 1994 Dec;6(12):1849–1856. doi: 10.1093/intimm/6.12.1849. [DOI] [PubMed] [Google Scholar]
  81. Yuan J., Shaham S., Ledoux S., Ellis H. M., Horvitz H. R. The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell. 1993 Nov 19;75(4):641–652. doi: 10.1016/0092-8674(93)90485-9. [DOI] [PubMed] [Google Scholar]
  82. Zauli G., Gibellini D., Celeghini C., Mischiati C., Bassini A., La Placa M., Capitani S. Pleiotropic effects of immobilized versus soluble recombinant HIV-1 Tat protein on CD3-mediated activation, induction of apoptosis, and HIV-1 long terminal repeat transactivation in purified CD4+ T lymphocytes. J Immunol. 1996 Sep 1;157(5):2216–2224. [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES