Heterogeneity of the human papillomavirus group

Abstract

Almost 70 years have elapsed between the discovery of the infectious nature of human papillomas (9) to the establishment of papillomaviruses as a heterogeneic group (30, 31, 50). The acquisition of detailed information was hampered by the lack of an adequate in vitro system to propagate human papillomaviruses. To date, 60 different types of human papillomaviruses (HPVs) have been isolated and characterized with the help of cloning systems in bacteria. In the majority of isolates, characterization has been based solely on the description of the DNA genome and its comparison to other known HPV prototypes. At one of the first international workshops on papillomaviruses (10), it was decided that a new type of HPV will be defined as an-7.9-kilobase closed circular, double-stranded DNA molecule which, by using liquid hybridization under stringent conditions, shows less than 50% homology to any of the known HPVs. The molecular organization of the HPV DNA genomes was defined on a comparative basis with that of the well-characterized bovine papillomavirus type 1 (BPV-1) genome (8). Data on the latter were much more readily obtainable because of the easy accessibility of BPV particles from lesions of experimentally infected animals. After subsequent sequencing of the BPV-1 genome, different genes were determined according to the open reading frames available. By means of colinear DNA comparisons and subsequent DNA sequencing, a genome organization for HPV analogous to that of BPV DNA was established. Although minor variations do occur, the HPVs all contain at least seven so-called early genes (El to E7) and two late genes (Li and L2). In addition, an upstream regulatory region harbors the regulatory sequences which appear to control most tran-scriptional events of the HPV genome.