INTERFERON INDUCTION BY HIV GLYCOPROTEIN-120 - ROLE OF THE V3 LOOP

被引:39
作者
ANKEL, H [1 ]
CAPOBIANCHI, MR [1 ]
CASTILLETTI, C [1 ]
DIANZANI, F [1 ]
机构
[1] UNIV ROMA LA SAPIENZA,INST VIROL,ROME,ITALY
关键词
D O I
10.1006/viro.1994.1617
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
We have studied the mechanism of IFN induction by HIV-1 in peripheral blood mononuclear cells (PBMC), using recombinant viral membrane glycoproteins as potential inducers. Whereas 8 nM HIVIIIB-derived gp120 resulted in IFN levels between 80 and 2000 IU/ml with PBMC from different donors, gp120 from the MN strain was not an inducer. Preincubation of HIVIIIB-gp120 with a monoclonal antibody (mAB) to its CD4 binding domain or of PBMC with a mAB to the gp120 binding domain of CD4 abolished IFN induction. Antibodies against the third extracellular domain of CD4 which did not block binding of gp120, however, were also inhibitory. Furthermore, several mABs to the third variable loop (V3) of HIVIIIB-gp120 also blocked IFN induction, suggesting an important role of V3 in this process. This was further supported by the inhibitory action of peptides homologous to complete or partial sequences of V3. We conclude that after binding of gp120 to its CD4 receptor the vs loop can be positioned close to the membrane of the responder cells by bending of gp120-occupied CD4 at its hinge region between extracellular domains 2 and 3. As a result vs is able to interact with a vs-specific ''secondary receptor'' on the membranes of these cells. We suggest that it is the latter interaction which triggers IFN induction. (C) 1994 academic Press, Inc.
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页码:34 / 43
页数:10
相关论文
共 48 条
  • [1] AMEGLIO F, 1994, CLIN EXP IMMUNOL, V95, P455, DOI 10.1111/j.1365-2249.1994.tb07018.x
  • [2] CRYSTAL-STRUCTURE OF DOMAIN-3 AND DOMAIN-4 OF RAT CD4 - RELATION TO THE NH2-TERMINAL DOMAINS
    BRADY, RL
    DODSON, EJ
    DODSON, GG
    LANGE, G
    DAVIS, SJ
    WILLIAMS, AF
    BARCLAY, AN
    [J]. SCIENCE, 1993, 260 (5110) : 979 - 983
  • [3] COORDINATE INDUCTION OF INTERFERON-ALPHA AND INTERFERON-GAMMA BY RECOMBINANT HIV-1 GLYCOPROTEIN-120
    CAPOBIANCHI, MR
    AMEGLIO, F
    FEI, PC
    CASTILLETTI, C
    MERCURI, F
    FAIS, S
    DIANZANI, F
    [J]. AIDS RESEARCH AND HUMAN RETROVIRUSES, 1993, 9 (10) : 957 - 962
  • [4] ACID-LABILE HUMAN INTERFERON ALPHA-PRODUCTION BY PERIPHERAL-BLOOD MONONUCLEAR-CELLS STIMULATED BY HIV-INFECTED CELLS
    CAPOBIANCHI, MR
    DEMARCO, F
    DIMARCO, P
    DIANZANI, F
    [J]. ARCHIVES OF VIROLOGY, 1988, 99 (1-2) : 9 - 19
  • [5] RECOMBINANT GLYCOPROTEIN-120 OF HUMAN-IMMUNODEFICIENCY-VIRUS IS A POTENT INTERFERON INDUCER
    CAPOBIANCHI, MR
    ANKEL, H
    AMEGLIO, F
    PAGANELLI, R
    PIZZOLI, PM
    DIANZANI, F
    [J]. AIDS RESEARCH AND HUMAN RETROVIRUSES, 1992, 8 (05) : 575 - 579
  • [6] ACID LABILITY IS NOT AN INTRINSIC PROPERTY OF INTERFERON-ALPHA INDUCED BY HIV-INFECTED CELLS
    CAPOBIANCHI, MR
    MATTANA, P
    MERCURI, F
    CONCIATORI, G
    AMEGLIO, F
    ANKEL, H
    DIANZANI, F
    [J]. JOURNAL OF INTERFERON RESEARCH, 1992, 12 (06): : 431 - 438
  • [7] CAPON DJ, 1991, ANNU REV IMMUNOL, V9, P649, DOI 10.1146/annurev.iy.09.040191.003245
  • [8] CAVACINI LA, 1993, J ACQ IMMUN DEF SYND, V6, P353
  • [9] DEVELOPMENT OF A SENSITIVE QUANTITATIVE FOCAL ASSAY FOR HUMAN IMMUNODEFICIENCY VIRUS INFECTIVITY
    CHESEBRO, B
    WEHRLY, K
    [J]. JOURNAL OF VIROLOGY, 1988, 62 (10) : 3779 - 3788
  • [10] EVALUATION OF MONOCLONAL-ANTIBODIES TO HIV-1 BY NEUTRALIZATION AND SEROLOGICAL ASSAYS - AN INTERNATIONAL COLLABORATION
    DSOUZA, MP
    DURDA, P
    HANSON, CV
    MILMAN, G
    [J]. AIDS, 1991, 5 (09) : 1061 - 1070