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

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2000年 / 97卷 / 26期

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

页码：14620 / 14625

页数：6