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' oligoadenylate synthetases. We examined the anticellular and antiviral activities of a specific member of that family, the P69 isozyme. P69 was expressed in human cells by transfection and shown to be localized primarily in the endoplasmic reticulum. For further studies, permanent cell lines expressing different levels of P69 or an enzymatically inactive mutant were isolated. Constitutive P69 expression caused inhibition of replication of encephalomyocarditis 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-expressing cells in the G1 phase of the cell cycle; cell-doubling time was increased by P69 expression; and there were many multinucleated cells in the P69-expressing line, indicating a defect in cytokinesis. Copyright 2000 Academic Press.