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 polyomavirus BK (BKV) was studied. Physiological concentrations of the synthetic glucocorticoid dexamethasone, progesterone R5020, or estrogen 17 beta-estradiol enhanced the permissivity of the host cell for BKV, resulting in an up to 11-fold (dexamethasone), 5-fold (progesterone), or 3-fold (17 beta-estradiol) higher virus yield. The increase in virus yield in dexamethasone-stimulated cells correlated with enhanced steady-state levels of viral transcripts. The late leader sequence of the BKV control region contains a hormone response unit composed of a nonconsensus glucocorticoid and/or progesterone response element (GRE/PRE) and a fully consensus estrogen response element (ERE). DNA-protein binding 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 assays, we were able to show that these sequences can mediate steroid hormone-induced gene expression. However, no cooperative transactivation effect between the BKV GRE/PRE-like motif and BKV ERE motif was observed. This BKV hormone response unit may play an important role in vivo by enhancing a productive BKV infection, and perhaps also by reactivating a latent infection, during physiological or pathological conditions accompanied by increased steroid hormone levels.
Moens
U
U
Department of Virology, University of Tromsøo, Norway.
Subramaniam
N
N
Johansen
B
B
Johansen
T
T
Traavik
T
T
D000818:Animals; D001739:BK Virus / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D001483:Base Sequence; D016384:Consensus Sequence; D003907:Dexamethasone / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D013256:Steroids / Q000494:pharmacology*; D013997:Time Factors; D015533:Transcriptional Activation; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
D004967:Estrogens; D012333:RNA, Messenger; D013256:Steroids; D011374:Progesterone; D003907:Dexamethasone