title: Effects of dimethyl prostaglandin A1 on herpes simplex virus and human immunodeficiency virus replication.
abstract: We have investigated the direct effect of dimethyl prostaglandin A1 (dmPGA1) on the replication of herpes simplex virus (HSV) and human immunodeficiency virus type 1 (HIV-1). dmPGA1 significantly inhibited viral replication in both HSV and HIV infection systems at concentrations of dmPGA1 that did not adversely alter cellular DNA synthesis. The 50% inhibitory concentration (ID50) for several HSV type 1 (HSV-1) strains ranged from 3.8 to 5.6 micrograms/ml for Vero cells and from 4.6 to 7.3 micrograms/ml for human foreskin fibroblasts. The ID50s for two HSV-2 strains varied from 3.8 to 4.5 micrograms/ml for Vero cells; the ID50 was 5.7 micrograms/ml for human foreskin fibroblasts. We found that closely related prostaglandins did not have the same effect on the replication of HSV; dmPGE2 and dmPGA2 caused up to a 60% increase in HSV replication compared with that in untreated virus-infected cells. HIV-1 replication in acutely infected T cells (VB line) and chronically infected macrophages was assessed by quantitative decreases in p24 concentration. The effective ID50s were 2.5 micrograms/ml for VB cells acutely infected with HIV-1 and 5.2 micrograms/m for chronically infected macrophages. dmPGA1 has an unusual broad-spectrum antiviral activity against both HSV and HIV-1 in vitro and offers a new class of potential therapeutic agents for in vivo use.
authors.affiliation: Research Service, Veterans Administration Medical Center, San Francisco, California 94121.
authors.forename: M
authors.initials: M
authors.lastname: Hughes-Fulford
authors.forename: M S
authors.initials: MS
authors.lastname: McGrath
authors.forename: D
authors.initials: D
authors.lastname: Hanks
authors.forename: S
authors.initials: S
authors.lastname: Erickson
authors.forename: L
authors.initials: L
authors.lastname: Pulliam
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D005347:Fibroblasts / Q000187:drug effects / Q000382:microbiology; D006678:HIV / Q000187:drug effects*; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology; D011455:Prostaglandins A, Synthetic / Q000494:pharmacology*; D018139:Simplexvirus / Q000187:drug effects*; D014709:Vero Cells / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D011455:Prostaglandins A, Synthetic; C078051:16,16-dimethylprostaglandin A1