Different effects of IFN gamma and IFN alpha/beta on "immediate early" gene expression of HSV-1.
The effects of interferon gamma (IFN gamma) on early steps of herpes simplex virus (Type 1; HSV-1) replication in primary cultures of splenic mouse macrophages were analyzed and compared to IFN alpha/beta. Pretreatment of macrophages with recombinant murine IFN gamma led to a dose-dependent reduction in the yield of progeny virus. Inhibition of protein synthesis was observed for HSV-1 alpha, beta and gamma-proteins. Expression of the "immediate early" (IE) gene IE3 (ICP4) was investigated in detail. Steady-state level of the RNA and transcriptional activity of the gene in IFN gamma-treated cells were comparable to control-infected cells except for a delay in their kinetics. This is in contrast to IFN alpha/beta, which leads to a stable decrease in IE3 transcripts. Since IFN gamma causes a stable decrease in the IE3 gene product ICP4, our data suggest a translational inhibition of HSV-1 IE gene expression in IFN gamma-treated macrophages. Thus, IFN gamma and IFN alpha/beta inhibit HSV-1 replication by different mechanisms which may lead to a synergistic enhancement of inhibition after combined treatment.
Klotzbücher
A
A
German Cancer Research Center, Institute for Virus Research, Deutsches Krebsforschungszentrum, Heidelberg.
Mittnacht
S
S
Kirchner
H
H
Jacobsen
H
H
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D005814:Genes, Viral / Q000235:genetics*; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages; D051379:Mice; D011994:Recombinant Proteins; D018139:Simplexvirus / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000096:biosynthesis
D007370:Interferon Type I; D011994:Recombinant Proteins; D014764:Viral Proteins; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma