Interferon-induced proteins in human fibroblasts and development of the antiviral state

Abstract

Treatment of human fibroblasts with interferon induces the synthesis of several proteins, as detected by incorporation of [35S]methionine followed by analysis of cell extracts by polyacrylamide gel electrophoresis. The induction of these proteins had features in common with the development of the antiviral effect [tested using vesicular stomatitis virus] of interferon, such as sensitivity to actinomycin D and cycloheximide when these compounds were added together with interferon, insensitivity to actinomycin D if the actinomycin D was added 2 h after the addition of interferon, similar dependence on interferon concentration and species specificity for interferon. When interferon treatment was given in the presence of cycloheximide and actinomycin D was added before the removal of cycloheximide, all 4 proteins were induced; apparently their inductions are coordinated. Labeling for 2 h periods at varying time intervals after the addition of interferon revealed that the synthesis of these proteins was induced within a few hours, peaked at different time intervals and was soon followed by a marked decline, suggesting that the mRNA for these proteins have short half-lives. This decline occurred despite the fact that the cells were continuously exposed to interferon and there was no measurable loss of interferon activity in the medium. The induction of these proteins is thus transient and apparently subject to further control.