INHIBITION OF HIV-1 REPLICATION BY CYCLOPENTENONE PROSTAGLANDINS IN ACUTELY INFECTED HUMAN-CELLS - EVIDENCE FOR A TRANSCRIPTIONAL BLOCK

Cyclopentenone prostaglandins (PGs) inhibit virus replication in sever al DNA and RNA virus models, in vitro and in vivo. In the present repo rt we demonstrate that the cyclopentenone prostaglandins PGA(1) and PG J(2) at nontoxic concentrations can dramatically suppress HIV-1 replic ation during acute infection in CEM-SS cells, PGs did not affect HIV-1 adsorption, penetration, reverse transcriptase activity nor viral DNA accumulation in HIV-1 infected cells. A dramatic reduction in HIV-1 m RNA levels was detected up to 48-72 h after infection (p.i.) in PG-tre ated cells, and HIV-1 protein synthesis was greatly reduced by a singl e PG-treatment up to 96 h p.i. Repeated PGA(1)-treatments were effecti ve in protecting CEM-SS cells by the cytopathic effect of the virus, a nd in dramatically reducing HIV-1 RNA levels up to 7 d after infection . The antiviral effect was not mediated by alterations in the expressi on of alpha-, beta-, or gamma-interferon, TNF alpha, TNF beta, IL6, an d IL10 in HIV-infected CEM-SS cells. The fact that prostaglandins are used clinically in the treatment of several diseases, suggests a poten tial use of cyclopentenone PGs in the treatment of HIV-infection.