Analysis of the early regulatory region of the human papovavirus BK

Abstract

BKV is a human papovavirus which latently infects a majority of the world population and whose DNA has been found in human tumor tissue. Along with simian virus 40 (SV40) and JCV, it is one of several highly homologous polyomaviruses which display distinct host ranges, tissue tropisms, and transformation potentials. Determination of these properties is thought to reside, in part, in the noncoding regulatory region of these viruses. We have studied the regulation of gene expression by the early promoter and enhancer of BKV. Our results show that the early promoter of BKV consists of elements found both to the early side of and within the proximal 18 bp of the first enhancer element itself. At least one BKV regulatory element appears to be downstream of the mRNA start sites. The BKV enhancer consists of two different types of elements, three direct repeats, and an element (denoted "c") found in the 30 bp to the late side of the distal repeat. When used with the BKV promoter the enhancer repeat elements were found to be redundant, optimal promoter activity requiring only two of the three repeats plus the c element. Using the heterologous SV40 promoter the optimal BKV enhancer consisted of either three repeats or two repeats plus the c element. Subfragments of the enhancer region were capable of partial activation of homologous and heterologous promoters. We conclude that the regulation of BKV early gene expression involves novel elements arranged in ways not previously described in other papovaviruses.