CD26-processed RANTES(3-68), but not intact RANTES, has potent anti-HIV-1 activity

被引:64
作者
Schols, D
Proost, P
Struyf, S
Wuyts, A
De Meester, I
Scharpé, S
Van Damme, J
De Clercq, E
机构
[1] Rega Inst Med Res, Lab Expt Chemotherapy, B-3000 Louvain, Belgium
[2] Rega Inst Med Res, Lab Mol Immunol, B-3000 Louvain, Belgium
[3] Univ Antwerp, Dept Clin Biochem, B-2610 Wilrijk, Belgium
关键词
CD26; RANTES; anti-HIV-1; activity; CCR5;
D O I
10.1016/S0166-3542(98)00039-4
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The natural CC-chemokine RANTES(3-68), missing two NH2-terminal residues, has been isolated from leukocytes and tumor cells, The highly specific aminopeptidase dipeptidyl peptidase IV (DPP IV), also called CD26, was shown to be responsible for this NH2-terminal truncation of RANTES. Here it is reported that CD26/DPP IV treatment of RANTES enhances its anti-HIV-1 activity. RANTES(3-68) inhibited infection of PBMC by M-tropic HIV-1 strains ten-fold more efficiently than intact RANTES, This difference in antiviral potency between intact and truncated RANTES was even more pronounced (at least 25-fold) in CCR5-transfected cell lines. In HOS.CD4.CCR5 transfected cells, RANTES(1-68) had virtually no anti-HIV-1 activity (IC50 > 130 nM), whereas RANTES(3-68) was a potent inhibitor of HIV-1 replication (IC50: 5.5 nM). The anti-HIV-1 activity of RANTES(1-68) in the different cell types correlated with the expression of CD26, Moreover, the addition of soluble CD26 together with RANTES(1-68) significantly enhanced the antiviral activity of RANTES in HOS.CD4.CCR5 cells (IC50: 13 nM). These observations point to an important role of CD26-mediated processing of RANTES in inhibiting the replication of CCR5-binding HIV strains in HIV-infected persons and in preventing the development of AIDS. (C) 1998 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:175 / 187
页数:13
相关论文
共 53 条
  • [1] CC CKRS: A RANTES, MIP-1 alpha, MIP-1 beta receptor as a fusion cofactor for macrophage-tropic HIV-1
    Alkhatib, G
    Combadiere, C
    Broder, CC
    Feng, Y
    Kennedy, PE
    Murphy, PM
    Berger, EA
    [J]. SCIENCE, 1996, 272 (5270) : 1955 - 1958
  • [2] HIV blocked by chemokine antagonist
    ArenzanaSeisdedos, F
    Virelizier, JL
    Rousset, D
    ClarkLewis, I
    Loetscher, P
    Moser, B
    Baggiolini, M
    [J]. NATURE, 1996, 383 (6599) : 400 - 400
  • [3] Multiple extracellular elements of CCR5 and HIV-1 entry: Dissociation from response to chemokines
    Atchison, RE
    Gosling, J
    Monteclaro, FS
    Franci, C
    Digilio, L
    Charo, IF
    Goldsmith, MA
    [J]. SCIENCE, 1996, 274 (5294) : 1924 - 1926
  • [4] INTERLEUKIN-8 RECEPTOR-BETA - THE ROLE OF THE CARBOXYL-TERMINUS IN SIGNAL-TRANSDUCTION
    BENBARUCH, A
    BENGALI, KM
    BIRAGYN, A
    JOHNSTON, JJ
    WANG, JM
    KIM, J
    CHUNTHARAPAI, A
    MICHIEL, DF
    OPPENHEIM, JJ
    KELVIN, DJ
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (16) : 9121 - 9128
  • [5] A seven-transmembrane domain receptor involved in fusion and entry of T-cell-tropic human immunodeficiency virus type 1 strains
    Berson, JF
    Long, D
    Doranz, BJ
    Rucker, J
    Jirik, FR
    Doms, RW
    [J]. JOURNAL OF VIROLOGY, 1996, 70 (09) : 6288 - 6295
  • [6] HIV-1-induced cell fusion is mediated by multiple regions within both the viral envelope and the CCR-5 co-receptor
    Bieniasz, PD
    Fridell, RA
    Aramori, I
    Ferguson, SSG
    Caron, MG
    Cullen, BR
    [J]. EMBO JOURNAL, 1997, 16 (10) : 2599 - 2609
  • [7] The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry
    Bleul, CC
    Farzan, M
    Choe, H
    Parolin, C
    ClarkLewis, I
    Sodroski, J
    Springer, TA
    [J]. NATURE, 1996, 382 (6594) : 829 - 833
  • [8] The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes
    Bleul, CC
    Wu, LJ
    Hoxie, JA
    Springer, TA
    Mackay, CR
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (05) : 1925 - 1930
  • [9] T-CELL ACTIVATION ANTIGEN, CD26, AS A COFACTOR FOR ENTRY OF HIV IN CD4+ CELLS
    CALLEBAUT, C
    KRUST, B
    JACOTOT, E
    HOVANESSIAN, AG
    [J]. SCIENCE, 1993, 262 (5142) : 2045 - 2050
  • [10] The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates
    Choe, H
    Farzan, M
    Sun, Y
    Sullivan, N
    Rollins, B
    Ponath, PD
    Wu, LJ
    Mackay, CR
    LaRosa, G
    Newman, W
    Gerard, N
    Gerard, C
    Sodroski, J
    [J]. CELL, 1996, 85 (07) : 1135 - 1148