Analysis of the corrected DNA sequence for the bovine papillomavirus type 4 (BPV4) genome revealed that there is no open reading frame (ORF) that might encode an E6 protein. The other two B subgroup bovine papillomaviruses, BPV3 and BPV6, were found to have the same arrangement of ORFs in this region as BPV4. Thus, we conclude that E6 functions are either not required by these viruses or are performed by another viral (or host) protein. Furthermore, the position that might be expected to be occupied by E6, between the long control region and the E7 ORF, contains the E8 ORF, which has the potential to encode a 42-residue polypeptide with considerable similarity to the E5 transforming protein of BPV1. Therefore, it appears that during the evolution of the B subgroup of BPVs, genomic rearrangements may have occurred resulting in the present layout of the early ORFs.
SUMMARYThe nucleotide sequence of bovine papillomavirus type 4 (BPV-4) was determined. The viral genome is 7261 base pairs long. Several overlapping open reading frames (ORFs) have been identified both on the basis of amino acid comparison with other papiUomaviruses and on their transcriptional pattern. Eight early ORFs (E 1 to 8) were recognized, coding for DNA replication and cell transformation functions, and three late ORFs (L1 to 3), coding for structural proteins. Like the E50RF of human papillomavirus type 6 the E50RF of BPV-4 is discontinuous. Unlike other papillomaviruses, the non-coding region upstream of the early ORFs (ncr-1) is short (385 base pairs), but there is another non-coding region (ncr-2) of nearly 500 base pairs between the L2 and L10RFs. Most of the putative regulatory sites are located in the ncr-1, although potential controlling elements are also found in other parts of the genome. Polyadenylation sites are present at the 3' end of both the early and the late transcription units. Comparison between the polypeptides of BPV-4 and other papillomaviruses showed that BPV-4 is evolutionarily closer to the epitheliotropic human and rabbit viruses than to BPV-1.
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