A highly conserved nucleotide string shared by all genomes of human papillomaviruses

Abstract

The nucleotide string TAAAACGAAAGT is the longest perfect homology shared by all sequenced human papillomavirus genomes. This nucleotide string, which was also found to be highly specific for human papillomavirus genomes, shares the same genomic position in all viral types (5' end of the E1 open reading frame) and putatively codes in every case for the same amino acids. One possible evolutionary model was used to estimate the probability of random occurrence of the nucleotide string in 10 human papillomavirus genomes. It assumed that the universal string had been subjected to the same mutation rate as the entire E1 open reading frame. The estimated probability was found to be very low, suggesting that the conservation of the string could not have resulted from random divergence and that its conservation among human papillomaviruses is likely to reflect the occurrence of biological constraints. It is speculated that this nucleotide string may be required to code for amino acids indispensable for the nuclear localization of E1-coded peptides or to bind cellular factors affecting viral replicative functions. Definitive evidence is expected to come from oligonucleotide-protein binding experiments and from site-directed mutagenesis of cloned HPV genomes. This motif, universal among human papillomaviruses, is being successfully used in the design of consensus primers from the early region.

Human papillomavirus in head and neck cancer: Molecular biology and clinicopathological correlations

“…High-risk oncogenic viruses include HPV 16,18,30, Intragenomic variability has also been studied in different HPV types. Approximately 2% of sequence variability occurs in the coding and 5% in the noncoding regions [53]. In general, the papillomavirus DNA genome has been estimated to evolve at rates approaching 1% variability per 100,000 years.…”

Human Papillomavirus and head and neck cancer: Epidemiology and molecular biology

“…These findings have led some investigators to suggest that all known HPV types are extremely stable and have existed in nearly identical form since the beginnings of the human species. 13,61 Only a handful of 70+ HPV types isolated to date have been consistently demonstrated in genital high-grade dysplasias and invasive carcinomas, leading to the concept of low-and highrisk HPV infections. 3,62 High-risk oncogenic viruses include HPV16, 18, 31, 33, and 35.…”

Detection of genital human papillomavirus by single-tube nested PCR and type-specific oligonucleotide hybridization

“…To allow for the detection of the different genital HPV types, we designed degenerate consensus primer pairs located in the most conserved regions of these parts of the HPV genome. In the E1 open reading frame, a highly conserved nucleotide sequence, shared by all papillomaviruses (5), was identified and chosen as one priming site. The different HPV types were distinguished by hybridization to oligonucleotides specific for 19 different genital HPV types.…”