Papil omavirus DNA Rep cation

The papillomaviruses constitute a large family of viruses that cause benign tumors (warts) in their hosts. In recent years, these viruses have been found to have substantial clinical importance (Syrjanen et al. 1987; zur Hausen 1991). The replication properties of papillomaviruses have been studied for a number of years; however, many results obtained in the early studies concerning both trans-acting factors and cis-acting elements required for replication have not been reproducible. Therefore, a clear picture of the viral replicon has emerged only during the last 5 years and the understanding of papillomavirus replication is relatively primitive compared to, for example, the well-studied SV40 system. For technical and historical reasons, the field has been dominated by studies of one particular member of the papillomavirus family, bovine papillomavirus (BPV), which has served as a prototype for the papillomaviruses. More recently, largely because of information obtained from the BPV system, it has become possible to develop systems to study the replication properties of several human papillomaviruses. In this chapter, I describe the BPV system in some detail and, from this point of reference, discuss the variations and differences that have been observed for replication of other papillomaviruses. The natural life cycle of papillomaviruses is complex and not understood in detail. However, in the basal cells of the papilloma, viral DNA is maintained in a latent form characterized by episomal replication at a relatively low copy number. At this stage, expression of viral capsid proteins cannot be detected. As the cells differentiate and migrate toward the outer layers’of the papilloma, substantially higher copy numbers and assembled virions can be detected (Stoler et al. 1990; Dollard et al. 1992; Meyers et al. 1992). The basis for all papillomavirus replication systems originates in the early observation that BPV can transform mouse cells in culture and that in the transformed cells, the viral DNA replicates as a plasmid with a modest copy number (Dvoretsky et al. 1980; Lancaster 1981; Law et al. 1981). Furthermore, the viral DNA is maintained over