Cell growth regulatory and antiviral effects of the P69 isozyme of 2-5 (A)synthetase

Among the many interferon-induced proteins that carry out multiple cellular functions of interferons is the family of enzymes called 2'-5' oligoadenyl ate synthetases. We examined the anticellular and antiviral activities of a specific member of that family, the P69 isozyme. P69 was expressed in huma n cells by transfection and shown to be localized primarily in the endoplas mic reticulum. For further studies, permanent cell lines expressing differe nt levels of P69 or an enzymatically inactive mutant were isolated. Constit utive P69 expression caused inhibition of replication of encephalomyocardit is virus but not of vesicular stomatitis virus, Sendai virus, or reovirus. Increasing levels of P69 expression also caused increasing perturbations in cell growth properties. There was increasing accumulations of the P69-expr essing cells in the G1 phase of the cell cycle; cell-doubling time was incr eased by P69 expression; and there were many multinucleated cells in the P6 9-expressing line, indicating a defect in cytokinesis. (C) 2000 Academic Pr ess.