PTH regulation of the human cytomegalovirus immediate-early gene promoter

Secondary hyperparathyroidism and human cytomegalovirus (hCMV) seropositivity are highly prevalent in patients undergoing renal transplantation, and both are linked to the development of chronic allograft nephropathy (CAN). We investigated the hypothesis that parathyroid hormone (PTH) 1–84 regulates hCMV immediate-early gene (IEG) promoter activation in proximal renal tubular cells. PTH 1–84 enhanced hCMV IEG promoter (−548 to +92) activity in opossum kidney cells. Deletion analysis from the 5′ end of the promoter localized the PTH 1–84 associated activity to the DNA sequence between −123 and −45. Mutation of an imperfect ATF/AP-1 DNA element within this region abrogated the PTH 1–84 effect and also strongly attenuated basal gene expression. Mobility shift analyses using this DNA element revealed that a member of the ATF-1 family was in the binding complex. In summary, we present evidence for a novel pathogenic role of PTH 1–84 in promoting hCMV immediate-early gene transcription.