Mechanism of interferon action Species specificity of interferon and of the interferon-mediated inhibitor of translation from mouse, monkey, and human cells

Abstract

The species specificity of interferon and of the interferon-mediated ribosome-associated inhibitor of translation from mouse fibroblast, African green monkey kidney, and human amnion cells was investigated. The following results were obtained: (1) The antiviral activity of mouse fibroblast, monkey kidney, and human leukocyte interferons was maximal on the homologous species of cells. Mouse interferon was not active on heterologous monkey cells, and monkey interferon was not active on mouse cells. Monkey and human interferons were almost equally active on heterologous human and monkey cells, respectively; mouse and human interferons were about 10 and 125 times more active, respectively, on their homologous cell species than on heterologous human and mouse cells. (2) Ribosomal salt-wash fractions prepared from interferon-treated mouse fibroblast, monkey kidney, and human amnion cells inhibited the translation of reovirus mRNA catalyzed by the mouse ascites cell-free protein-synthesizing system prepared from untreated ascites cells. The corresponding fractions prepared from untreated mouse and human cells either did not affect or stimulated the translation of reovirus mRNA. Ribosomal washes from untreated monkey kidney cells were inhibitory, but not as inhibitory as washes from interferon-treated cells. (3) The concentration of KCl required to release the interferon-mediated ribosome-associated inhibitor from ribosomes of mouse fibroblast cells was higher than that required for ribosomes from human amnion and monkey kidney cells. (4) The translation of both methylated and unmethylated reovirus mRNA catalyzed by the mouse ascites cell-free system was inhibited by the mouse fibroblast ribosome-associated interferon-mediated factor. These results suggest that the interferon-mediated ribosome-associated antiviral factor(s) is not species specific, even though certain interferons are relatively species specific.