Sequence homologies between bovine papillomavirus genomes mapped by a novel low-stringency heteroduplex method

The bovine papillomaviruses (BPVs) types 1, 2, and 5 cause fibropapillomas whereas BPVs types 3, 4, and 6 cause true papillomas. A novel method of heteroduplex mapping at low stringency of hybridisation has identified the position and relative orientation of distantly related sequences in the genomes of these viruses. The genomes of BPV-1 and BPV-2 are closely related but both show a high degree of sequence divergence from the BPV-5 genome. A 1.25-kb sequence adjacent to the unique BamHI site of the BPV-5 genome hybridised to BPV-1 and to the equivalent region of BPV-2. The hybridising sequence in the BPV-1 genome mapped to the C-terminal region of the E1 open reading frame (ORF) and the N-terminal region of the E2 ORF. The BPV-3, BPV-4, and BPV-6 genomes show moderate homology to each other but minimal homology to the fibropapillomavirus genomes. Low-stringency heteroduplex mapping revealed that overlapping sequences in the BPV-1 E1 and L1 ORFs (or the equivalent regions in BPV-2) hybridised to sequences in BPV-3, BPV-4, and BPV-6. Hybrid regions were less than 1 kb long and were sometimes interrupted by short nonhybridising segments. The hybridising sequences in BPV-3 and BPV-4 are positioned in a way that parallels the spacing of the E1 and L1 ORFs in BPV-1. These data suggest that the bovine fibropapilloma viruses and true papilloma viruses share a similar genomic organization, but have undergone extensive sequence divergence.