HIV-1 Tat protein mimicry of chemokines

被引:244
作者
Albini, A
Ferrini, S
Benelli, R
Sforzini, S
Giunciuglio, D
Aluigi, MG
Proudfoot, AEI
Alouani, S
Wells, TNC
Mariani, G
Rabin, RL
Farber, JM
Noonan, DM
机构
[1] Ist Nazl Ric Canc, Ctr Biotecnol Avanzate, I-16132 Genoa, Italy
[2] Glaxo Wellcome Res & Dev Ltd, Geneva Biomed Res Inst, CH-1228 Geneva, Switzerland
[3] Univ Genoa, Dipartimento Med Interna, I-16132 Genoa, Italy
[4] NIAID, NIH, Bethesda, MD 20892 USA
基金
英国惠康基金;
关键词
D O I
10.1073/pnas.95.22.13153
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The HIV-1 Tat protein is a potent chemoattractant for monocytes, We observed that Tat shows conserved amino acids corresponding to critical sequences of the chemokines, a family of molecules known for their potent ability to attract monocytes, Synthetic Tat and a peptide (CysL(24-51)) encompassing the "chemokine-like" region of Tat induced a rapid and transient Ca2+ influx in monocytes and macrophages, analogous to beta-chemokines, Both monocyte migration and Ca2+ mobilization were pertussis toxin sensitive and cholera toxin insensitive. Cross-desensitization studies indicated that Tat shares receptors with MCP-1, MCP-3, and eotaxin, Tat was able to displace binding of beta-chemokines from the beta-chemokine receptors CCR2 and CCR3, but not CCR1, CCR4, and CCR5, Direct receptor binding experiments with the CysL(24-51) peptide confirmed binding to cells transfected with CCR2 and CCR3. HIV-1 Tat appears to mimic beta-chemokine features, which may serve to locally recruit chemokine receptor-expressing monocytes/macrophages toward HIV producing cells and facilitate activation and infection.
引用
收藏
页码:13153 / 13158
页数:6
相关论文
共 37 条
[1]  
Albini A, 1996, ONCOGENE, V12, P289
[2]   The angiogenesis induced by HIV-1 Tat protein is mediated by the Flk-1/KDR receptor on vascular endothelial cells [J].
Albini, A ;
Soldi, R ;
Giunciuglio, D ;
Giraudo, E ;
Benelli, R ;
Primo, L ;
Noonan, D ;
Salio, M ;
Camussi, G ;
Rockl, W ;
Bussolino, F .
NATURE MEDICINE, 1996, 2 (12) :1371-1375
[3]   Identification of a novel domain of HIV Tat involved in monocyte chemotaxis [J].
Albini, A ;
Benelli, R ;
Giunciuglio, D ;
Cai, T ;
Mariani, G ;
Ferrini, S ;
Noonan, DM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (26) :15895-15900
[4]   STRUCTURAL STUDIES OF HIV-1 TAT PROTEIN [J].
BAYER, P ;
KRAFT, M ;
EJCHART, A ;
WESTENDORP, M ;
FRANK, R ;
ROSCH, P .
JOURNAL OF MOLECULAR BIOLOGY, 1995, 247 (04) :529-535
[5]   Monocyte-derived dendritic cells and monocytes migrate to HIV-Tat RGD and basic peptides [J].
Benelli, R ;
Mortarini, R ;
Anichini, A ;
Giunciuglio, D ;
Noonan, DM ;
Montalti, S ;
Tacchetti, C ;
Albini, A .
AIDS, 1998, 12 (03) :261-268
[6]  
Berger EA, 1997, AIDS, V11, pS3
[7]   Impaired monocyte migration and reduced type 1 (Th1) cytokine responses in C-C chemokine receptor 2 knockout mice [J].
Boring, L ;
Gosling, J ;
Chensue, SW ;
Kunkel, SL ;
Farese, RV ;
Broxmeyer, HE ;
Charo, IF .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (10) :2552-2561
[8]   IDENTIFICATION OF AN ARG-GLY-ASP (RGD) CELL-ADHESION SITE IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TRANSACTIVATION PROTEIN, TAT [J].
BRAKE, DA ;
DEBOUCK, C ;
BIESECKER, G .
JOURNAL OF CELL BIOLOGY, 1990, 111 (03) :1275-1281
[9]   Chemokines and HIV-1 second receptors: The therapeutic connection [J].
Cairns, JS ;
D'Souza, MP .
NATURE MEDICINE, 1998, 4 (05) :563-568
[10]   MOLECULAR-CLONING AND FUNCTIONAL EXPRESSION OF 2 MONOCYTE CHEMOATTRACTANT PROTEIN-1 RECEPTORS REVEALS ALTERNATIVE SPLICING OF THE CARBOXYL-TERMINAL TAILS [J].
CHARO, IF ;
MYERS, SJ ;
HERMAN, A ;
FRANCI, C ;
CONNOLLY, AJ ;
COUGHLIN, SR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (07) :2752-2756