Relationship between the antiviral effects of interferons and their abilities to depress cytochrome P-450.
Several hybrid human interferons have now been constructed by recombinant DNA techniques. Two of these hybrid interferons, IFN-alpha AD(Bgl) and IFN-alpha AD(Pvu) differ by only three amino acids, but IFN-alpha AD(Bgl) was fifteen times more potent than IFN-alpha AD(Pvu) in antiviral activity towards infection of mouse L-929 cells by vesicular stomatitis virus. Only the hybrid with the greater antiviral activity in the mouse depressed cytochrome P-450, aminopyrine N-demethylase and benzo[a]pyrene hydroxylase in the liver. These experiments demonstrate that minor changes in amino acid structure not only have a major effect on the antiviral properties of interferon but also influence the ability of interferon to depress cytochrome P-450 in the liver.
D000633:Aminopyrine N-Demethylase / Q000096:biosynthesis; D000818:Animals; D001579:Benzopyrene Hydroxylase / Q000096:biosynthesis; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004274:DNA, Recombinant / Q000378:metabolism; D005796:Genes; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology
D004274:DNA, Recombinant; D007370:Interferon Type I; D003577:Cytochrome P-450 Enzyme System; D001579:Benzopyrene Hydroxylase; D000633:Aminopyrine N-Demethylase; D011070:Poly I-C