Inhibition of HIV-1 transcription by cyclopentenone prostaglandin A(1) in Jurkat T lymphocytes

Cyclopentenone prostaglandins inhibit virus replication in several DNA and RNA Virus models. In this report we investigated the effect of prostaglandi n A(1) (PGA(1)) on HIV-1 transcription in human CD4+ Jurkat T lymphocyte ce lls. A dramatic reduction of HIV-1 RNA levels was detected up to seven days post infection in both unstimulated and phorbol 12-mystrate 13-acetate (PM A)-stimulated cells treated with PGA(1). PGA(1) treatment of cells was also effective in inhibiting the transcription of a chloramphenicol acetyltrans ferase (CAT) reporter gene, under the control of HIV-1 LTR, in Jurkat-Tat c ells. We also show that PGA(1) induced the synthesis of 70-kDa heat-shock p rotein (HSP70) in this cell system and the induction correlated with the dr ug-antiviral activity. PGA(1) was also found to induce the loss of the tumo r suppressor p53 protein, in the "proliferative" conformation, in a time co rrelation with the induction of the HSP70 As the "proliferative" p53 has be en involved in the positive trans-activation of the HIV-1 LTR its depletion could contribute to the inhibitory mechanisms of PGA(1) on virus transcrip tion.