Home LiteratureArticle Details
PMID: 10708425 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Human immunodeficiency virus type 1 vpr induces apoptosis through caspase activation.

Journal of virology ·Vol. 74 ·No. 7 ·2000-04-00 ·Pages 3105-11

Stewart SA, Poon B, Song JY, Chen IS

Abstract

Human immunodeficiency virus type 1 (HIV-1) Vpr is a 96-amino-acid protein that is found associated with the HIV-1 virion. Vpr induces cell cycle arrest at the G(2)/M phase of the cell cycle, and this arrest is followed by apoptosis. We examined the mechanism of Vpr-induced apoptosis and found that HIV-1 Vpr-induced apoptosis requires the activation of a number of cellular cysteinyl aspartate-specific proteases (caspases). We demonstrate that ectopic expression of anti-apoptotic viral proteins, which inhibit caspase activity, and addition of synthetic peptides, which represent caspase cleavage sites, can inhibit Vpr-induced apoptosis. Finally, inhibition of caspase activity and subsequent inhibition of apoptosis results in increased viral expression, suggesting that therapeutic strategies aimed at reducing Vpr-induced apoptosis in vivo require careful consideration.

MeSH Terms
Apoptosis/physiology Caspases/metabolism Cell Line Enzyme Activation Gene Products, vpr/physiology HIV-1/physiology Humans Virus Replication vpr Gene Products, Human Immunodeficiency Virus
Chemicals
Gene Products, vpr vpr Gene Products, Human Immunodeficiency Virus Caspases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Stewart S A
Departments of Microbiology and Immunology and Medicine, UCLA School of Medicine and Jonsson Comprehensive Cancer Center, Los Angeles, California 90095, USA.
Poon B
Song J Y
Chen I S
References (59)
59 references, click to expand
  1. Programmed cell death in AIDS-related HIV and SIV infections.
    AIDS Res Hum Retroviruses. 1993 Jun;9(6):553-63 PMID: 8102239
  2. An apoptosis-inhibiting baculovirus gene with a zinc finger-like motif.
    J Virol. 1993 Apr;67(4):2168-74 PMID: 8445726
  3. Dicing with death: dissecting the components of the apoptosis machinery.
    Trends Biochem Sci. 1994 Jan;19(1):26-30 PMID: 8140617
  4. Apoptosis: a mechanism of cell killing by influenza A and B viruses.
    J Virol. 1994 Jun;68(6):3667-73 PMID: 8189504
  5. Inhibition of interleukin-1 beta converting enzyme by the cowpox virus serpin CrmA. An example of cross-class inhibition.
    J Biol Chem. 1994 Jul 29;269(30):19331-7 PMID: 8034697
  6. The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in nondividing host cells.
    Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7311-5 PMID: 8041786
  7. A general method for the generation of high-titer, pantropic retroviral vectors: highly efficient infection of primary hepatocytes.
    Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9564-8 PMID: 7937806
  8. Suppression of apoptosis in insect cells stably transfected with baculovirus p35: dominant interference by N-terminal sequences p35(1-76).
    J Virol. 1994 Dec;68(12):7728-37 PMID: 7966562
  9. The human immunodeficiency virus type 1 vpr gene prevents cell proliferation during chronic infection.
    J Virol. 1995 Feb;69(2):882-8 PMID: 7815556
  10. Viral dynamics in human immunodeficiency virus type 1 infection.
    Nature. 1995 Jan 12;373(6510):117-22 PMID: 7529365
  11. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection.
    Nature. 1995 Jan 12;373(6510):123-6 PMID: 7816094
  12. Identification of residues in the N-terminal acidic domain of HIV-1 Vpr essential for virion incorporation.
    Virology. 1995 Feb 20;207(1):297-302 PMID: 7871742
  13. Progression to AIDS in the absence of a gene for vpr or vpx.
    J Virol. 1995 Apr;69(4):2378-83 PMID: 7884883
  14. 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):6304-13 PMID: 7666531
  15. 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):6705-11 PMID: 7474080
  16. 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):6859-64 PMID: 7474100
  17. A leucine triplet repeat sequence (LXX)4 in p6gag is important for Vpr incorporation into human immunodeficiency virus type 1 particles.
    J Virol. 1995 Nov;69(11):6873-9 PMID: 7474102
  18. Mutagenic analysis of human immunodeficiency virus type 1 Vpr: role of a predicted N-terminal alpha-helical structure in Vpr nuclear localization and virion incorporation.
    J Virol. 1995 Nov;69(11):7032-44 PMID: 7474123
  19. Mutational analysis of cell cycle arrest, nuclear localization and virion packaging of human immunodeficiency virus type 1 Vpr.
    J Virol. 1995 Dec;69(12):7909-16 PMID: 7494303
  20. Human cytomegalovirus IE1 and IE2 proteins block apoptosis.
    J Virol. 1995 Dec;69(12):7960-70 PMID: 7494309
  21. Bcl-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis.
    EMBO J. 1995 Dec 15;14(24):6136-47 PMID: 8557033
  22. Role of the karyopherin pathway in human immunodeficiency virus type 1 nuclear import.
    J Virol. 1996 Feb;70(2):1027-32 PMID: 8551560
  23. HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time.
    Science. 1996 Mar 15;271(5255):1582-6 PMID: 8599114
  24. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector.
    Science. 1996 Apr 12;272(5259):263-7 PMID: 8602510
  25. Human immunodeficiency virus type 1 cell cycle control: Vpr is cytostatic and mediates G2 accumulation by a mechanism which differs from DNA damage checkpoint control.
    J Virol. 1996 Apr;70(4):2324-31 PMID: 8642659
  26. Vpr-induced cell cycle arrest is conserved among primate lentiviruses.
    J Virol. 1996 Apr;70(4):2516-24 PMID: 8642681
  27. Human isolates of dengue type 1 virus induce apoptosis in mouse neuroblastoma cells.
    J Virol. 1996 Jun;70(6):4090-6 PMID: 8648748
  28. Effect of human immunodeficiency virus type 1 protein R (vpr) gene expression on basic cellular function of fission yeast Schizosaccharomyces pombe.
    J Virol. 1996 Sep;70(9):5821-6 PMID: 8709199
  29. Regulation of apoptosis by viral gene products.
    J Virol. 1997 Mar;71(3):1739-46 PMID: 9032302
  30. In vitro and in vivo tumor growth suppression by HIV-1 Vpr.
    DNA Cell Biol. 1997 Feb;16(2):137-43 PMID: 9052734
  31. The inhibition of pro-apoptotic ICE-like proteases enhances HIV replication.
    Nat Med. 1997 Mar;3(3):333-7 PMID: 9055863
  32. Target protease specificity of the viral serpin CrmA. Analysis of five caspases.
    J Biol Chem. 1997 Mar 21;272(12):7797-800 PMID: 9065443
  33. The role of the Caspase family of cysteine proteases in apoptosis.
    Semin Immunol. 1997 Feb;9(1):35-49 PMID: 9106306
  34. Baculovirus inhibitor of apoptosis functions at or upstream of the apoptotic suppressor P35 to prevent programmed cell death.
    J Virol. 1997 Jun;71(6):4509-16 PMID: 9151843
  35. Human immunodeficiency virus type 1 Vpr induces apoptosis following cell cycle arrest.
    J Virol. 1997 Jul;71(7):5579-92 PMID: 9188632
  36. HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway.
    Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9825-30 PMID: 9275210
  37. HIV-1 Vpr suppresses immune activation and apoptosis through regulation of nuclear factor kappa B.
    Nat Med. 1997 Oct;3(10):1117-23 PMID: 9334723
  38. Human immunodeficiency virus type 1 Vpr interacts with HHR23A, a cellular protein implicated in nucleotide excision DNA repair.
    J Virol. 1997 Dec;71(12):9732-42 PMID: 9371639
  39. HIV-1 Vpr increases viral expression by manipulation of the cell cycle: a mechanism for selection of Vpr in vivo.
    Nat Med. 1998 Jan;4(1):65-71 PMID: 9427608
  40. HIV-1 Vpr interacts with the nuclear transport pathway to promote macrophage infection.
    Genes Dev. 1998 Jan 15;12(2):175-85 PMID: 9436978
  41. The HIV-1 vpr protein acts as a negative regulator of apoptosis in a human lymphoblastoid T cell line: possible implications for the pathogenesis of AIDS.
    J Exp Med. 1998 Feb 2;187(3):403-13 PMID: 9449720
  42. The fight of viruses against apoptosis.
    Curr Opin Genet Dev. 1998 Feb;8(1):82-7 PMID: 9529610
  43. Human immunodeficiency virus type 1 Vpr is a positive regulator of viral transcription and infectivity in primary human macrophages.
    J Exp Med. 1998 Apr 6;187(7):1103-11 PMID: 9529326
  44. 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
  45. An inducible human immunodeficiency virus type 1 (HIV-1) vector which effectively suppresses HIV-1 replication.
    J Virol. 1999 Sep;73(9):7671-7 PMID: 10438857
  46. Lentiviral delivery of HIV-1 Vpr protein induces apoptosis in transformed cells.
    Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):12039-43 PMID: 10518572
  47. Mutational analysis of the human immunodeficiency virus vpr open reading frame.
    J Virol. 1989 Sep;63(9):4110-4 PMID: 2474678
  48. Identification of HIV-1 vpr product and function.
    J Acquir Immune Defic Syndr. 1990;3(1):11-8 PMID: 2136707
  49. Open reading frame vpr of simian immunodeficiency virus encodes a virion-associated protein.
    J Virol. 1990 Nov;64(11):5688-93 PMID: 2145446
  50. Pseudotype formation of murine leukemia virus with the G protein of vesicular stomatitis virus.
    J Virol. 1991 Mar;65(3):1202-7 PMID: 1847450
  51. Apoptosis as a mechanism of cell death in cultured T lymphoblasts acutely infected with HIV-1.
    J Clin Invest. 1991 May;87(5):1710-5 PMID: 2022741
  52. Prevention of apoptosis by a baculovirus gene during infection of insect cells.
    Science. 1991 Nov 29;254(5036):1388-90 PMID: 1962198
  53. The cytopathic effect of HIV is associated with apoptosis.
    Virology. 1991 Dec;185(2):829-39 PMID: 1683728
  54. Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages.
    J Immunol. 1992 Apr 1;148(7):2207-16 PMID: 1545126
  55. Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme.
    Cell. 1992 May 15;69(4):597-604 PMID: 1339309
  56. Induction of cell differentiation by human immunodeficiency virus 1 vpr.
    Cell. 1993 Feb 26;72(4):541-50 PMID: 8440020
  57. Conversion of lytic to persistent alphavirus infection by the bcl-2 cellular oncogene.
    Nature. 1993 Feb 25;361(6414):739-42 PMID: 8441470
  58. Ultrastructural features of fetal erythroid precursors infected with parvovirus B19 in vitro: evidence of cell death by apoptosis.
    J Pathol. 1993 Feb;169(2):213-20 PMID: 8445486
  59. Programmed death of T cells in human immunodeficiency virus infection. No correlation with progression to disease.
    J Clin Invest. 1994 Mar;93(3):982-8 PMID: 8132784
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/jvi.74.7.3105-3111.2000
Published
2000-04-00
Pages
3105-11
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC111809
Subset
IM
Grants
NCI NIH HHS · T32 CA09056 · United States
NCI NIH HHS · CA 70018 · United States
NCI NIH HHS · T32 CA009056 · United States
NCI NIH HHS · R01 CA070018 · United States
NIAID NIH HHS · R01 AI043190 · United States
NIAID NIH HHS · T32 AI007388 · United States
NIAID NIH HHS · AI 43190 · United States
External Links
PubMed source DOI: 10.1128/jvi.74.7.3105-3111.2000 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