MEMBRANE-EXPRESSED HIV ENVELOPE GLYCOPROTEIN HETERODIMER IS A POWERFUL INDUCER OF CELL-DEATH IN UNINFECTED CD4(+) TARGET-CELLS

被引:44
作者
LAURENTCRAWFORD, AG [1 ]
COCCIA, E [1 ]
KRUST, B [1 ]
HOVANESSIAN, AG [1 ]
机构
[1] INST PASTEUR,CNRS,UA 1157,UNITE VIROL & IMMUNOL CELLULAIRE,F-75724 PARIS 15,FRANCE
来源
RESEARCH IN VIROLOGY | 1995年 / 146卷 / 01期
关键词
AIDS; HIV; T LYMPHOCYTE; CD4; APOPTOSIS; MEMBRANE EXPRESSION; CELL KILLING; HIV-1 ENV GENE PRODUCTS; V3; LOOP; SYNCYTIA; GLYCOPROTEINS GP120-GP41 COMPLEX;
D O I
10.1016/0923-2516(96)80585-1
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
HIV infection of CD4(+) T cells in culture results in the production of virus and induction of cell killing by apoptosis. Such a cytopathic effect is observed during infection with syncytium-inducing or non-syncytium-inducing HIV isolates. Apoptosis is triggered by the interaction of the cell membrane-expressed HIV envelope glycoprotein heterodimer gp120-gp41 complex (external and transmembrane glycoprotein complex) with the CD4 receptor. Here we demonstrate an experimental model for the induction of apoptosis independent of HIV infection, using transiently transfected HeLa cells with the HIV1 env gene as effector cells and the CD4(+) MOLT4-T4 T cells as target cells. Results obtained confirm that the induction of apoptosis requires the membrane expression of the two HIV env gene products, gp120 and gp41. Single amino acid point mutations of the envelope products that affect binding to the CD4 receptor or the fusion process abrogate the capacity of the gp120-gp41 complex to induce apoptosis. Interestingly, a point mutation in the V3 loop which inhibits fusion without affecting CD4 binding also results in the abrogation of apoptosis. These observations indicate that the induction of apoptosis is an intrinsic property of the cell membrane-expressed gp120-gp41 complex, and thus should be considered as one of the functions of HIV env gene products.
引用
收藏
页码:5 / 17
页数:13
相关论文
共 53 条
[1]   PROGRAMMED CELL-DEATH AND AIDS - FROM HYPOTHESIS TO EXPERIMENT [J].
AMEISEN, JC .
IMMUNOLOGY TODAY, 1992, 13 (10) :388-391
[2]   DISSOCIATION OF UNINTEGRATED VIRAL-DNA ACCUMULATION FROM SINGLE-CELL LYSIS INDUCED BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 [J].
BERGERON, L ;
SODROSKI, J .
JOURNAL OF VIROLOGY, 1992, 66 (10) :5777-5787
[3]   HIV-INDUCED SYNCYTIUM FORMATION REQUIRES THE FORMATION OF CONJUGATES BETWEEN VIRUS-INFECTED AND UNINFECTED T-CELLS INVITRO [J].
BUSSO, M ;
THORNTHWAITE, J ;
RESNICK, L .
AIDS, 1991, 5 (12) :1425-1432
[4]   APOPTOSIS AND DISEASE [J].
CARSON, DA ;
RIBEIRO, JM .
LANCET, 1993, 341 (8855) :1251-1254
[5]   PARTICIPATION OF TYROSINE PHOSPHORYLATION IN THE CYTOPATHIC EFFECT OF HUMAN-IMMUNODEFICIENCY-VIRUS .1. [J].
COHEN, DI ;
TANI, Y ;
TIAN, H ;
BOONE, E ;
SAMELSON, LE ;
LANE, HC .
SCIENCE, 1992, 256 (5056) :542-545
[6]  
COHEN JJ, 1993, IMMUNOL TODAY, V14, P126, DOI 10.1016/0167-5699(93)90214-6
[7]   SINGLE AMINO-ACID CHANGES IN HIV ENVELOPE AFFECT VIRAL TROPISM AND RECEPTOR-BINDING [J].
CORDONNIER, A ;
MONTAGNIER, L ;
EMERMAN, M .
NATURE, 1989, 340 (6234) :571-574
[8]   HIV INTERACTIONS WITH CD4 - A CONTINUUM OF CONFORMATIONS AND CONSEQUENCES [J].
EIDEN, LE ;
LIFSON, JD .
IMMUNOLOGY TODAY, 1992, 13 (06) :201-206
[9]   MASSIVE COVERT INFECTION OF HELPER T-LYMPHOCYTES AND MACROPHAGES BY HIV DURING THE INCUBATION PERIOD OF AIDS [J].
EMBRETSON, J ;
ZUPANCIC, M ;
RIBAS, JL ;
BURKE, A ;
RACZ, P ;
TENNERRACZ, K ;
HAASE, AT .
NATURE, 1993, 362 (6418) :359-362
[10]   THE REV GENE-PRODUCT OF THE HUMAN IMMUNODEFICIENCY VIRUS AFFECTS ENVELOPE-SPECIFIC RNA LOCALIZATION [J].
EMERMAN, M ;
VAZEUX, R ;
PEDEN, K .
CELL, 1989, 57 (07) :1155-1165