A STEROID-HORMONE RESPONSE UNIT IN THE LATE LEADER OF THE NONCODING CONTROL REGION OF THE HUMAN POLYOMAVIRUS BK CONFERS ENHANCED HOST-CELL PERMISSIVITY

The effect of steroid hormones on multiplication of the human polyomav irus BK (BKV) was studied. Physiological concentrations of the synthet ic glucocorticoid dexamethasone, progesterone R5020, or estrogen 17 be ta-estradiol enhanced the permissivity of the host cell for BKV, resul ting in an up to 11-fold (dexamethasone), 5-fold (progesterone), or 3- fold (17 beta-estradiol) higher virus yield. The increase in virus yie ld in dexamethasone-stimulated cells correlated with enhanced steady-s tate levels of viral transcripts. The late leader sequence of the BKV control region contains a hormone response unit composed of a nonconse nsus glucocorticoid and/or progesterone response element (GRE/PRE) and a fully consensus estrogen response element (ERE). DNA-protein bindin g studies showed that the glucocorticoid receptor and the progesterone receptor bound to this BKV GRE/PRE-like sequence, while the estrogen receptor could bind to the BKV ERE motif. By transient transfection as says, we were able to show that these sequences can mediate steroid ho rmone-induced gene expression. However, no cooperative transactivation effect between the BKV GRE/PRE-like motif and BKV ERE motif was obser ved. This BKV hormone response unit may play an important role in vivo by enhancing a productive BKV infection, and perhaps also by reactiva ting a latent infection, during physiological or pathological conditio ns accompanied by increased steroid hormone levels.