produced in cells inoculated with NDV at low moi. In the present study we compared levels of F and Le inter- feron mRNA in theGM-258 and FS-4 fibroblast cell ...
Proc. NatI. Acad. Sc. USA Vol. 77, No. 9, pp. 5341-5345, September 1980 Cell Biology
Le interferon mRNA from human fibroblasts IXenopus laevis oocytes/poly(I).poly(C)/Newcastle disease virus/interferon induction/regulation of transcription and translation] RoY H. L. PANG, TERESA G. HAYES, AND JAN VILtEK New York University School of Medicine, New York, New York 10016
Communicated by Saul Krugman, June 20,1980
ABSTRACT Human F and Le interferon can be clearly distinguished on the basis of different antigenic properties and host range. After inoculation with Newcastle disease virus (NDV), GM-258 fibroblasts produced Le as well as F interferon; in contrast, only F interferon was detectable after stimulation with poly(I)poly(C). Polyadenylylated mRNA isolated from fibroblasts induced with poly(I)poly(C) or NDV was injected into Xenopus Iaevis oocytes and the interferon activities thus produced were analyzed. Only F interferon production was demonstrable in oocytes injected with mRNA from cells induced with poly(I)poly(C), whereas both F and Le interferons were made in oocytes injected with mRNA from NDV-induced cultures. The time course of accumulation of F and Le interferon mRNAs in NDV-induced cells corresponded to the kinetics of F and Le interferon synthesis in intact cells. The ratio of F and Le interferons made in oocytes was similar to that observed in intact GM-258 cells. F and Le interferon mRNA activities isolated from GM-258 cells could not be separated by sucrose density gradient centrifugation. However, the profile of F mRNA activity was more heterogeneous and its peak sedimented somewhat more slowly than that of Le interferon mRNA. These results suggest that the varying ratios of F and Le interferon synthesis in different cells after different modes of stimulation are determined at the level of mRNA. The induction mechanisms of F and Le interferon mRNA synthesis appear to be closely related but not identical. Interferon induction is a suitable model system for the study of regulation of gene expression in eukaryotic cells. Three major types of interferon can be clearly distinguished on the basis of different physicochemical characteristics, antigenic properties, and host range (1-3). They have been provisionally termed Le, F, and "immune" interferons. Recent evidence indicates that the NH2-terminal amino acid sequences of human Le and F interferons are completely different (4, 5). Le interferon is the major species present in preparations of "leukocyte" interferon-i.e., interferon produced in lymphocytes stimulated with Sendai or Newcastle disease virus (NDV). F interferon is produced preferentially by many nonlymphoid cells, including human diploid cells stimulated with poly(I)poly(C) or with viruses. A single cell population may produce more than one interferon type. For example, primary cultures of human buffy coat cells stimulated with Sendai virus produce a small amount (
