Inhibition of HIV-1 transcription by cyclopentenone prostaglandin A1 in Jurkat T lymphocytes.
Cyclopentenone prostaglandins inhibit virus replication in several DNA and RNA virus models. In this report we investigated the effect of prostaglandin A1 (PGA1) on HIV-1 transcription in human CD4+ Jurkat T lymphocyte cells. 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 (PMA)-stimulated cells treated with PGA1- PGA1 treatment of cells was also effective in inhibiting the transcription of a chloramphenicol acetyltransferase (CAT) reporter gene, under the control of HIV-1 LTR, in Jurkat-Tat cells. We also show that PGA1 induced the synthesis of 70-kDa heat-shock protein (HSP70) in this cell system and the induction correlated with the drug-antiviral activity. PGA1 was also found to induce the loss of the tumor suppressor p53 protein, in the "proliferative" conformation, in a time correlation with the induction of the HSP70 As the "proliferative" p53 has been involved in the positive trans-activation of the HIV-1 LTR its depletion could contribute to the inhibitory mechanisms of PGA1 on virus transcription.
Carattoli
A
A
Laboratory of Bacteriology and Medical Mycology, Istituto Superiore di Sanità, Roma, Italy.
Fortini
D
D
Rozera
C
C
Giorgi
C
C
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D015500:Chloramphenicol O-Acetyltransferase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015696:Gene Products, tat / Q000187:drug effects / Q000235:genetics; D016325:HIV Long Terminal Repeat / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D011454:Prostaglandins A / Q000494:pharmacology*; D012367:RNA, Viral / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D018840:HSP70 Heat-Shock Proteins; D011454:Prostaglandins A; D012367:RNA, Viral; D016159:Tumor Suppressor Protein p53; D054322:tat Gene Products, Human Immunodeficiency Virus; D015500:Chloramphenicol O-Acetyltransferase; D013755:Tetradecanoylphorbol Acetate; C100573:prostaglandin A1