INTERFERON - CELLULAR INTERACTIONS: INDUCTION OF PROTEINS, ANTIPROLIFERATIVE AND OTHER PHENOTYPIC EFFECTS (PROTEIN KINASE)
Abstract
The antiviral, antiproliferative, and protein-inducing activities of rat fibroblast-derived interferon (RfIFN) were examined in four rat cell lines (RFA-1, JS, IEC6, and C6) and one mouse cell line (L929B). A pronounced reduction in virus yield, viral RNA synthesis, and viral protein synthesis were noted in both rat and mouse cells treated with RfIFN prior to vesicular stomatitis virus (VSV) infection. RfIFN also exhibited a strong antiproliferative effect on rat cells. Approximately a 50% reduction in cell number was seen in rat cell cultures exposed to 100 u/ml RfIFN. In contrast, only a mild antiproliferative action was observed in L929B cells treated with the same dose of RfIFN (<12% reduction). A 50% inhibition of proliferation was seen only at a dose of 2000 u/ml. Elevated levels of two double-stranded (ds) RNA-dependent enzyme activities were also evident in extracts of RfIFN-treated rat and mouse cells. Depending on the cell type, and length and dosage of RfIFN treatment, a 5-93 fold increase in 2,5A synthetase levels were noted. In interferon treated cells a dsRNA-dependent protein kinase (PK) enhanced the phosphorylation of two proteins that had M.W.s of 35 kD and 63 kD in rat cells. In mouse cells the larger protein had a M.W. of 67 kD. The 35 kD was indirectly shown to be the smallest subunit of the eukaryotic initiation factor. The interferon-enhanced synthesis of several other proteins with approximate M.W.s of 13.5, 15, 16, 50, and 78 kD were shown by one- and two-dimensional gel electrophoresis. These proteins were observed in both rat and mouse cells. The effects of long term culture of rat cells in the continuous presence of RfIFN in the growth medium were also examined. The results indicate that, in the three cell lines studied, prolonged treatment with RfIFN selects a population of cells whose growth rates are unaffected by interferon. A cell line that was cultured for over 150 passages with RfIFN was also resistant to the antiviral effect. The examination of interferon-induced proteins in the above cell lines suggests a lack of correlation between the antiproliferative state and the two dsRNA-dependent enzyme activities. However, a correlation between the other induced proteins and the antiviral effect was evident in the cell line that was resistant to the antiviral effect.
Subject Area
Biology
Recommended Citation
THAMPOE, IMMAC JUVENTINUS, "INTERFERON - CELLULAR INTERACTIONS: INDUCTION OF PROTEINS, ANTIPROLIFERATIVE AND OTHER PHENOTYPIC EFFECTS (PROTEIN KINASE)" (1986). ETD Collection for Fordham University. AAI8628544.
https://research.library.fordham.edu/dissertations/AAI8628544
