Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4+ T cell hyperactivation and HIV type 1 replication

被引:24
作者
Secchiero, P
Zella, D
Curreli, S
Mirandola, P
Capitani, S
Gallo, RC
Zauli, G
机构
[1] Univ Maryland, Inst Biotechnol, Inst Human Virol, Baltimore, MD 21201 USA
[2] Univ Ferrara, Dept Morphol & Embryol, Human Anat Sect, I-44100 Ferrara, Italy
[3] Univ G DAnnunzio, Inst Normal Human Morphol, I-66013 Chieti, Italy
关键词
D O I
10.1073/pnas.011512398
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
We show here that HIV type 1 (HIV-1)Tat protein, in combination with anti-CD3/CD28 mAbs, promotes IL-2 production and proliferation of primary CD4(+) T lymphocytes, obtained from HIV-1-seronegative donors. This effect was observed when Tat was immobilized on a solid support, but it was not observed with soluble Tat Such hyperactivation was accomplished by recruiting the rolipram-sensitive cyclic nucleoside phosphodiesterase 4 and resulted in increased susceptibility to HIV-1 infection. Accordingly, rolipram potently inhibited HIV-1 replication in cultures stimulated by anti-CD3/CD28 +/- Tat These results add to the concept that decreasing Tat activity is an important addition to anti-HIV-1 therapy, and they suggest a target for anti-HIV-1 chemotherapy, phosphodiesterase 4.
引用
收藏
页码:14620 / 14625
页数:6
相关论文
共 41 条
[1]   HIV-1 Tat protein mimicry of chemokines [J].
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 .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (22) :13153-13158
[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]  
ANASTASSIOU ED, 1992, J IMMUNOL, V148, P2845
[4]   ROLIPRAM, A SPECIFIC TYPE-IV PHOSPHODIESTERASE INHIBITOR, IS A POTENT INHIBITOR OF HIV-1 REPLICATION [J].
ANGEL, JB ;
SAGET, BM ;
WALSH, SP ;
GRETEN, TF ;
DINARELLO, CA ;
SKOLNIK, PR ;
ENDRES, S .
AIDS, 1995, 9 (10) :1137-1144
[5]   THE TAT PROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1, A GROWTH-FACTOR FOR AIDS KAPOSI-SARCOMA AND CYTOKINE-ACTIVATED VASCULAR CELLS, INDUCES ADHESION OF THE SAME CELL-TYPES BY USING INTEGRIN RECEPTORS RECOGNIZING THE RGD AMINO-ACID-SEQUENCE [J].
BARILLARI, G ;
GENDELMAN, R ;
GALLO, RC ;
ENSOLI, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (17) :7941-7945
[6]   CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES - FUNCTIONAL IMPLICATIONS OF MULTIPLE ISOFORMS [J].
BEAVO, JA .
PHYSIOLOGICAL REVIEWS, 1995, 75 (04) :725-748
[7]   Extracellular HIV-1 Tat protein activates phosphatidylinositol 3- and Akt/PKB kinases in CD4(+) T lymphoblastoid Jurkat cells [J].
Borgatti, P ;
Zauli, G ;
Colamussi, ML ;
Gibellini, D ;
Previati, M ;
Cantley, LL ;
Capitani, S .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1997, 27 (11) :2805-2811
[8]  
Boykins RA, 1999, J IMMUNOL, V163, P15
[9]   Control of SHIV-89.6P-infection of cynomolgus monkeys by HIV-1 Tat protein vaccine [J].
Cafaro, A ;
Caputo, A ;
Fracasso, C ;
Maggiorella, MT ;
Goletti, D ;
Baroncelli, S ;
Pace, M ;
Sernicola, L ;
Koanga-Mogtomo, ML ;
Betti, M ;
Borsetti, A ;
Belli, R ;
Åkerblom, L ;
Corrias, F ;
Buttò, S ;
Heeney, J ;
Verani, P ;
Titti, F ;
Ensoli, B .
NATURE MEDICINE, 1999, 5 (06) :643-650
[10]  
COFFEY RG, 1983, CANCER RES, V43, P150