Effect of interferon on replication of herpes simplex virus types 1 and 2 in human macrophages.
Macrophages derived from human peripheral blood and cultured for 1 week were permissive for the replication of herpes simplex virus (HSV) types 1 and 2. Low titers of interferon (IFN) were produced after virus infection. The yield of infectious virions was reduced by pretreatment of cells with natural and recombinant IFN-alpha and natural IFN-beta. Recombinant and natural IFN-gamma exhibited very low antiviral activity. Treatment of cells with IFN-gamma mixed with IFN-alpha or with IFN-beta did not result in a synergistic inhibition of virus yield. We studied the synthesis of HSV type 1- and HSV type 2-coded proteins in macrophages treated with IFN-beta. Induction of the HSV beta-protein DNA polymerase was strongly inhibited in IFN-treated cells in a dose-dependent manner. As shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, other beta- and gamma-proteins of HSV were inhibited as well. Immunofluorescence studies revealed a strong inhibition of the expression of immediate early alpha-protein ICP4. The results indicate that IFN acts early during the viral replication cycle to inhibit the synthesis of HSV alpha- and beta-proteins.
D002478:Cells, Cultured; D004259:DNA-Directed DNA Polymerase / Q000096:biosynthesis; D004347:Drug Interactions; D005090:Exodeoxyribonucleases / Q000096:biosynthesis; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000382:microbiology; D011994:Recombinant Proteins / Q000494:pharmacology; D018139:Simplexvirus / Q000187:drug effects / Q000502:physiology*; D014764:Viral Proteins; D014779:Virus Replication / Q000187:drug effects*
D007370:Interferon Type I; D011994:Recombinant Proteins; D014764:Viral Proteins; D004259:DNA-Directed DNA Polymerase; D005090:Exodeoxyribonucleases; C043417:DNA polymerase, Simplexvirus