Reversible suppression of mouse mammary tumor virus replication by prolonged glucocorticoid exposure

Expression of mouse mammary tumor virus (MuMTV) in MJY-alpha mammary tumor cells was only transiently stimulated by exposure to 14 microM hydrocortisone (HC). Short-term HC treatment for 24-48 hours resulted in twofold-to-fivefold increases in levels of MuMTV polypeptide synthesis, MuMTV surface antigen expression, and MuMTV production. HC treatment also induced quantitative alterations in glycosylation of MuMTV precursors Pr79env and Pr76env. In contrast, prolonged exposure to 14 microM HC for 14-21 days decreased MuMTV polypeptide synthesis, surface antigen expression, and virion production to levels similar to untreated MJY-alpha cells. The pattern of MuMTV precursor glycosylation following prolonged HC treatment was identical to that detected in unexposed control cultures. Attenuation of glucocorticoid-mediated MuMTV stimulation was reversed either by exposure of treated cells to elevated (28 or 60 microM) concentrations of HC or by intermediate passage of treated cells in HC-free medium, suggesting additional levels of control of MuMTV replication.