Inhibition of HIV-1 transcription by cyclopentenone prostaglandin A1 in Jurkat T lymphocytes.

Abstract

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.

• Authors: A Carattoli, D Fortini, C Rozera, C Giorgi
• Journal: Journal of biological regulators and homeostatic agents (J Biol Regul Homeost Agents) 2000 Jul-Sep Vol. 14 Issue 3 Pg. 209-16 ISSN: 0393-974X [Print] Italy
• PMID: 11037055 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Gene Products, tat
• HSP70 Heat-Shock Proteins
• Prostaglandins A
• RNA, Viral
• Tumor Suppressor Protein p53
• tat Gene Products, Human Immunodeficiency Virus
• Chloramphenicol O-Acetyltransferase
• Tetradecanoylphorbol Acetate
• prostaglandin A1

Topics

• CD4-Positive T-Lymphocytes (drug effects)
• Chloramphenicol O-Acetyltransferase (drug effects, genetics, metabolism)
• Gene Products, tat (drug effects, genetics)
• HIV Long Terminal Repeat (drug effects)
• HIV-1 (drug effects, genetics)
• HSP70 Heat-Shock Proteins (biosynthesis, drug effects)
• Humans
• Jurkat Cells (drug effects, metabolism, virology)
• Prostaglandins A (pharmacology)
• RNA, Viral (drug effects)
• Tetradecanoylphorbol Acetate (pharmacology)
• Transcription, Genetic
• Tumor Suppressor Protein p53 (drug effects, metabolism)
• Virus Replication (drug effects)
• tat Gene Products, Human Immunodeficiency Virus