Effects of dimethyl prostaglandin A1 on herpes simplex virus and human immunodeficiency virus replication.
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.
Hughes-Fulford
M
M
Research Service, Veterans Administration Medical Center, San Francisco, California 94121.
McGrath
M S
MS
Hanks
D
D
Erickson
S
S
Pulliam
L
L
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
D000998:Antiviral Agents; D011455:Prostaglandins A, Synthetic; C078051:16,16-dimethylprostaglandin A1