Home LiteratureArticle Details
PMID: 10655504 Published · ppublish English Comparative Study Journal Article

HIV-1 envelope induces activation of caspase-3 and cleavage of focal adhesion kinase in primary human CD4(+) T cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 3 ·2000-02-01 ·Pages 1178-83

Cicala C, Arthos J, Rubbert A, Selig S, Wildt K, Cohen OJ, Fauci AS

Abstract

Binding of HIV type 1 (HIV-1) envelope glycoproteins to the surface of a CD4(+) T cell transduces intracellular signals through the primary envelope receptor, CD4, and a coreceptor, either CCR5 or CXCR4. Furthermore, envelope-CD4(+) cell interactions increase rates of apoptosis in peripheral blood mononuclear cells (PBMCs). We demonstrate that in primary T lymphocytes, recombinant HIV-1 envelope proteins induce the activation of caspase-3 and caspase-6, which belong to a family of cysteine proteases that, upon activation, promote programmed cell death. Envelope-mediated activation of caspase-3 and caspase-6 depended on envelope-CD4 receptor interactions; CCR5-utilizing as well as CXCR4-utilizing envelopes elicited this response. Focal adhesion kinase (FAK) is a substrate of both caspase-3 and caspase-6, and inactivation of FAK by these caspases promotes apoptosis. En-velope treatment of lymphocytes led to the cleavage of FAK in a manner consistent with caspase-mediated cleavage.

MeSH Terms
Apoptosis CD4-Positive T-Lymphocytes/enzymology,virology CD8-Positive T-Lymphocytes/enzymology,virology Caspase 3 Caspase 6 Caspases/metabolism Cell Adhesion Molecules/metabolism Enzyme Activation Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Gene Products, env/physiology HIV-1/physiology Humans Phosphorylation Protein Processing, Post-Translational Protein-Tyrosine Kinases/metabolism
Chemicals
Cell Adhesion Molecules Gene Products, env Protein-Tyrosine Kinases Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases PTK2 protein, human CASP3 protein, human CASP6 protein, human Caspase 3 Caspase 6 Caspases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Cicala C
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. CCicala@nih.gov
Arthos J
Rubbert A
Selig S
Wildt K
Cohen O J
Fauci A S
References (67)
67 references, click to expand
  1. Human immunodeficiency virus type 1 Vpr induces apoptosis following cell cycle arrest.
    J Virol. 1997 Jul;71(7):5579-92 PMID: 9188632
  2. Cytotoxic monocytes in the blood of HIV type 1-infected subjects destroy targeted T cells in a CD95-dependent fashion.
    AIDS Res Hum Retroviruses. 1997 Jul 20;13(11):953-60 PMID: 9223411
  3. CD4 cross-linking (CD4XL) induces RAS activation and tumor necrosis factor-alpha secretion in CD4+ T cells.
    Blood. 1997 Aug 15;90(4):1588-93 PMID: 9269777
  4. Cleavage of focal adhesion kinase by caspases during apoptosis.
    J Biol Chem. 1997 Oct 10;272(41):26056-61 PMID: 9325343
  5. Induction of apoptosis after expression of PYK2, a tyrosine kinase structurally related to focal adhesion kinase.
    J Cell Biol. 1997 Oct 20;139(2):529-39 PMID: 9334354
  6. Interleukin-1 beta converting enzyme-like protease involvement in Fas-induced and activation-induced peripheral blood T cell apoptosis in HIV infection. TNF-related apoptosis-inducing ligand can mediate activation-induced T cell death in HIV infection.
    J Exp Med. 1997 Oct 20;186(8):1365-72 PMID: 9334376
  7. Macrophage-tropic HIV and SIV envelope proteins induce a signal through the CCR5 chemokine receptor.
    Nature. 1997 Oct 30;389(6654):981-5 PMID: 9353123
  8. Signal transduction due to HIV-1 envelope interactions with chemokine receptors CXCR4 or CCR5.
    J Exp Med. 1997 Nov 17;186(10):1793-8 PMID: 9362541
  9. Distinct mechanisms trigger apoptosis in human immunodeficiency virus type 1-infected and in uninfected bystander T lymphocytes.
    J Virol. 1998 Jan;72(1):660-70 PMID: 9420271
  10. Caspase-mediated cleavage of focal adhesion kinase pp125FAK and disassembly of focal adhesions in human endothelial cell apoptosis.
    J Exp Med. 1998 Feb 16;187(4):579-86 PMID: 9463408
  11. HIV-1 gp120 accelerates Fas-mediated activation-induced human lamina propria T cell apoptosis.
    J Clin Immunol. 1998 Jan;18(1):39-47 PMID: 9475352
  12. Differential susceptibility to activation-induced apoptosis among peripheral Th1 subsets: correlation with Bcl-2 expression and consequences for AIDS pathogenesis.
    J Immunol. 1998 Apr 1;160(7):3194-206 PMID: 9531275
  13. Apoptotic cell death upon contact of CD4+ T lymphocytes with HIV glycoprotein-expressing cells is mediated by caspases but bypasses CD95 (Fas/Apo-1) and TNF receptor 1.
    J Immunol. 1997 Dec 1;159(11):5246-52 PMID: 9548463
  14. Vpr stimulates viral expression and induces cell killing in human immunodeficiency virus type 1-infected dividing Jurkat T cells.
    J Virol. 1998 Jun;72(6):4686-93 PMID: 9573232
  15. Induction of lymphomonocyte activation by HIV-1 glycoprotein gp120. Possible role in AIDS pathogenesis.
    J Biol Regul Homeost Agents. 1996 Oct-Dec;10(4):83-91 PMID: 9604776
  16. ICE/CED3-like proteases as therapeutic targets for the control of inappropriate apoptosis.
    Nat Biotechnol. 1996 Mar;14(3):297-301 PMID: 9630889
  17. Caspases cleave focal adhesion kinase during apoptosis to generate a FRNK-like polypeptide.
    J Biol Chem. 1998 Jul 3;273(27):17102-8 PMID: 9642276
  18. Mechanisms controlling cellular suicide: role of Bcl-2 and caspases.
    Cell Mol Life Sci. 1998 May;54(5):427-45 PMID: 9645223
  19. HIV-1 Tat induces neuronal death via tumor necrosis factor-alpha and activation of non-N-methyl-D-aspartate receptors by a NFkappaB-independent mechanism.
    J Biol Chem. 1998 Jul 10;273(28):17852-8 PMID: 9651389
  20. Cell cycle arrest by Vpr in HIV-1 virions and insensitivity to antiretroviral agents.
    Science. 1998 Jul 10;281(5374):266-9 PMID: 9657723
  21. Fas/FasL interaction is not involved in apoptosis of activated CD4+ T cells upon HIV-1 infection in vitro.
    J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Aug 1;18(4):307-15 PMID: 9704935
  22. Caspases: enemies within.
    Science. 1998 Aug 28;281(5381):1312-6 PMID: 9721091
  23. Diminished spontaneous apoptosis in lymphocytes from human immunodeficiency virus-infected long-term nonprogressors.
    J Infect Dis. 1998 Sep;178(3):669-79 PMID: 9728534
  24. Apoptosis of CD8+ T cells is mediated by macrophages through interaction of HIV gp120 with chemokine receptor CXCR4.
    Nature. 1998 Sep 10;395(6698):189-94 PMID: 9744279
  25. Nef harbors a major determinant of pathogenicity for an AIDS-like disease induced by HIV-1 in transgenic mice.
    Cell. 1998 Oct 16;95(2):163-75 PMID: 9790524
  26. Human immunodeficiency virus type 1 Nef protein sensitizes CD4(+) T lymphoid cells to apoptosis via functional upregulation of the CD95/CD95 ligand pathway.
    Blood. 1999 Feb 1;93(3):1000-10 PMID: 9920849
  27. T cell apoptosis in HIV infection: mechanisms and relevance for AIDS pathogenesis.
    Results Probl Cell Differ. 1998;24:233-48 PMID: 9949839
  28. Human immunodeficiency virus type 1 Tat induces apoptosis and increases sensitivity to apoptotic signals by up-regulating FLICE/caspase-8.
    J Virol. 1999 Mar;73(3):1956-63 PMID: 9971775
  29. Neuroprotection by a caspase inhibitor in acute bacterial meningitis.
    Nat Med. 1999 Mar;5(3):298-302 PMID: 10086385
  30. Emerging roles of caspase-3 in apoptosis.
    Cell Death Differ. 1999 Feb;6(2):99-104 PMID: 10200555
  31. Dephosphorylation of focal adhesion kinase (FAK) and loss of focal contacts precede caspase-mediated cleavage of FAK during apoptosis in renal epithelial cells.
    J Biol Chem. 1999 May 7;274(19):13328-37 PMID: 10224094
  32. Induction of phosphorylation and intracellular association of CC chemokine receptor 5 and focal adhesion kinase in primary human CD4+ T cells by macrophage-tropic HIV envelope.
    J Immunol. 1999 Jul 1;163(1):420-6 PMID: 10384144
  33. Qualitative analysis of immune function in patients with the acquired immunodeficiency syndrome. Evidence for a selective defect in soluble antigen recognition.
    N Engl J Med. 1985 Jul 11;313(2):79-84 PMID: 2582258
  34. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone.
    J Virol. 1986 Aug;59(2):284-91 PMID: 3016298
  35. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection.
    Cell. 1996 Aug 9;86(3):367-77 PMID: 8756719
  36. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene.
    Nature. 1996 Aug 22;382(6593):722-5 PMID: 8751444
  37. Human immunodeficiency virus type 1 gp120 induces anergy in human peripheral blood lymphocytes by inducing interleukin-10 production.
    J Virol. 1996 Aug;70(8):4953-60 PMID: 8764000
  38. Crosslinking CD4 by human immunodeficiency virus gp120 primes T cells for activation-induced apoptosis.
    J Exp Med. 1992 Oct 1;176(4):1099-106 PMID: 1402655
  39. A model for the selective loss of major histocompatibility complex self-restricted T cell immune responses during the development of acquired immune deficiency syndrome (AIDS).
    J Immunol. 1986 Oct 15;137(8):2514-21 PMID: 3489767
  40. HTLV-III expression in infected lymph nodes and relevance to pathogenesis of lymphadenopathy.
    Am J Pathol. 1986 Dec;125(3):436-42 PMID: 3642987
  41. HIV-1 GP120-mediated immune suppression and lymphocyte destruction in the absence of viral infection.
    J Immunol. 1989 May 1;142(9):3091-7 PMID: 2468713
  42. Human immunodeficiency virus type 1 envelope glycoprotein gp120 produces immune defects in CD4+ T lymphocytes by inhibiting interleukin 2 mRNA.
    Proc Natl Acad Sci U S A. 1990 Mar;87(6):2379-83 PMID: 2315327
  43. Sequence analysis and acute pathogenicity of molecularly cloned SIVSMM-PBj14.
    Nature. 1990 Jun 14;345(6276):636-40 PMID: 1971917
  44. HIV-1 tropism for mononuclear phagocytes can be determined by regions of gp120 outside the CD4-binding domain.
    Nature. 1990 Nov 1;348(6296):69-73 PMID: 2172833
  45. Relative resistance of primary HIV-1 isolates to neutralization by soluble CD4.
    Am J Med. 1991 Apr 10;90(4A):22S-26S PMID: 2018048
  46. Virions of primary human immunodeficiency virus type 1 isolates resistant to soluble CD4 (sCD4) neutralization differ in sCD4 binding and glycoprotein gp120 retention from sCD4-sensitive isolates.
    J Virol. 1992 Jan;66(1):235-43 PMID: 1727487
  47. Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals.
    J Exp Med. 1992 Feb 1;175(2):331-40 PMID: 1346269
  48. Human immunodeficiency virus gp120 and derived peptides activate protein tyrosine kinase p56lck in human CD4 T lymphocytes.
    Eur J Immunol. 1993 Mar;23(3):600-7 PMID: 7680610
  49. Programmed cell death in AIDS-related HIV and SIV infections.
    AIDS Res Hum Retroviruses. 1993 Jun;9(6):553-63 PMID: 8102239
  50. Membrane expression of HIV envelope glycoproteins triggers apoptosis in CD4 cells.
    AIDS Res Hum Retroviruses. 1993 Aug;9(8):761-73 PMID: 8105835
  51. HIV-1 gp120 and anti-gp120 induce reversible unresponsiveness in peripheral CD4 T lymphocytes.
    J Acquir Immune Defic Syndr. 1994 Apr;7(4):340-8 PMID: 7907660
  52. Direct involvement of extracellular HIV-1 virions in the apoptosis of CD8+ lymphocytes: a two-step model.
    Med Hypotheses. 1994 Mar;42(3):159-68 PMID: 8057970
  53. Cross-linking of CD4 molecules upregulates Fas antigen expression in lymphocytes by inducing interferon-gamma and tumor necrosis factor-alpha secretion.
    Blood. 1994 Oct 15;84(8):2622-31 PMID: 7522637
  54. Genetic variation of HIV type 1 in four World Health Organization-sponsored vaccine evaluation sites: generation of functional envelope (glycoprotein 160) clones representative of sequence subtypes A, B, C, and E. WHO Network for HIV Isolation and Characterization.
    AIDS Res Hum Retroviruses. 1994 Nov;10(11):1359-68 PMID: 7888189
  55. Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120.
    Nature. 1995 Jun 8;375(6531):497-500 PMID: 7539892
  56. Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes.
    Nat Med. 1995 Feb;1(2):129-34 PMID: 7585008
  57. The role of CD4 in HIV envelope-mediated pathogenesis.
    Curr Top Microbiol Immunol. 1996;205:159-79 PMID: 8575195
  58. HIV-1 Tat protein and its inhibitor Ro 24-7429 inhibit lymphocyte proliferation and induce apoptosis in peripheral blood mononuclear cells from healthy donors.
    Cell Immunol. 1996 Apr 10;169(1):40-6 PMID: 8612292
  59. Protection against lethal simian immunodeficiency virus SIVsmmPBj14 disease by a recombinant Semliki Forest virus gp160 vaccine and by a gp120 subunit vaccine.
    J Virol. 1996 Mar;70(3):1953-60 PMID: 8627721
  60. Envelope glycoproteins of human immunodeficiency virus type 1: profound influences on immune functions.
    Microbiol Rev. 1996 Jun;60(2):386-406 PMID: 8801439
  61. Human immunodeficiency virus type 1 Nef protein on the cell surface is cytocidal for human CD4+ T cells.
    FEBS Lett. 1996 Sep 9;393(1):105-8 PMID: 8804435
  62. Clustered localization of oligomeric Nef protein of human immunodeficiency virus type 1 on the cell surface.
    FEBS Lett. 1996 Oct 21;395(2-3):257-61 PMID: 8898107
  63. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression.
    Nat Med. 1996 Nov;2(11):1240-3 PMID: 8898752
  64. CD4-dependent, antibody-sensitive interactions between HIV-1 and its co-receptor CCR-5.
    Nature. 1996 Nov 14;384(6605):184-7 PMID: 8906796
  65. Activation-induced peripheral blood T cell apoptosis is Fas independent in HIV-infected individuals.
    Int Immunol. 1996 Aug;8(8):1311-7 PMID: 8918700
  66. Differential susceptibility to HIV-GP120-sensitized apoptosis in CD4+ T-cell clones with different T-helper phenotypes: role of CD95/CD95L interactions.
    Blood. 1997 Jan 15;89(2):558-69 PMID: 9002959
  67. gp120 is present on the plasma membrane of apoptotic CD4 cells prepared from lymph nodes of HIV-1-infected individuals: an immunoelectron microscopic study.
    AIDS. 1997 Jan;11(1):27-32 PMID: 9110072
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.97.3.1178
Email
ccicala@nih.gov
Published
2000-02-01
Pages
1178-83
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC15560
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.97.3.1178 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2