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Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14620-5.

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

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1
Institute of Human Virology, University of Maryland Biotechnology Institute, 725 West Lombard Street, S307, Baltimore, MD 21201-1192, USA.

Abstract

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.

PMID:
11114167
PMCID:
PMC18968
DOI:
10.1073/pnas.011512398
[Indexed for MEDLINE]
Free PMC Article
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