A common function for polyoma virus large-T and papillomavirus E1 proteins?

Abstract

Nucleotide sequencing has revealed a common genetic organization for three papillomaviruses: BPV-1 (bovine papillomavirus type 1), HPV-1 (human papillomavirus type 1a) and HPV-6 (human papillomavirus type 6b)^1–4. Several open reading frames, corresponding to as yet uncharacterized proteins, were observed in these genomes in the region that is required for oncogenic transformation by BPV-1 and for plasmidial maintenance of its genome⁵. The longest of these frames, E1, is also the most conserved between the three viruses^3,4 ; we have compared the amino acid sequence of its putative product (‘E1 protein’) with those of the large-T proteins of three polyoma viruses^6–11 and report here significant homologies in their carboxy-terminal halves, extending for over 200 amino acids. Moreover, similar secondary structures were predicted^12,13 in this region, especially in two blocks of homologous residues, which correspond in the large-T proteins of polyoma and simian virus 40 (SV40) viruses to sites involved in the ATPase^14,15 and nucleotide-binding activities¹⁶. These observations suggest that the papillomavirus E1 proteins might have a function in common with the polyoma virus large-T proteins (which are required for the initiation of viral DNA replication¹⁷). As it was suggested recently that the E1 gene product is involved in maintaining the BPV-1 genome as a plasmid in transformed cells^18,19, we speculate that the structural features conserved in these otherwise very different viruses are general characteristics of eukaryotic proteins involved in the control of DNA replication.