Effect of interferon on replication of herpes simplex virus types 1 and 2 in human macrophages

Abstract

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. aor 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.