Prevalence of HPV16 E1‐1374^63nt variants in Greek women

Abstract

Recent studies have focused on sequence variation of the HPV16 E1 gene. The present study investigates the prevalence of E1-1374^63nt duplication in the Greek population, and the sequence variation at the 5' end of the E1 and E6 genes from samples that harbored this genetic alteration. Fifty HPV16 positive cervical samples, derived from Greek patients were investigated. The 5' end of the E1 gene was amplified through PCR and the variant amplicons were cloned, sequenced, and bioinformatically analyzed for selective pressure. The E1-1374^63nt duplication was identified in 24% of the examined samples, with the same prevalence in both high and low-grade cervical malignancies. The E1-1374^63nt duplication was linked to the European variant lineage (x² = 5.076, P < 0.024) and it was significantly associated with the nucleotide variation A1053C (x² = 23.102, P < 0.0001). Molecular evolution analyses anticipate that the E1-1374^63nt duplication induces functional constraints on the 5' end of E1 gene, and it is proposed that this duplication might not affect negatively the function or structure of the E1 protein. The E1-1374^63nt duplication is prevalent in the Greek population, whereas the A1053C variation might constitute a significant marker for the characterization of the E1-1374^63nt variant in the Greek population, thus providing significant information about viral pathogenicity.

Genetic variability of the HPV16 early genes and LCR. Present and future perspectives

“…This duplication is significantly associated with the E1 sequence variation A1053C (E63D), as well (Ref. 93). The A1053C is located upstream of the E1-1374^63nt duplication resulting in the amino acid substitution E63D (Ref.…”

“…Interestingly, in the HPV16 E1 gene the region between nucleotides 1311-1374 (E1-1374^63nt duplication) is found to be duplicated in tandem, leading to a duplication of the region between amino acids 150 and 170 (21 amino acids) into the N-terminal domain of E1 protein. To date, this duplication has been observed in patients derived from China, Croatia, Slovenia and Greece and was strongly associated with the E6 T350G nucleotide variation (Refs [90][91][92][93]. This duplication is significantly associated with the E1 sequence variation A1053C (E63D), as well (Ref.…”

“…The A1053C is located upstream of the E1-1374^63nt duplication resulting in the amino acid substitution E63D (Ref. 93). It is important to highlight that the E1-1374^63nt duplication was preferentially identified in LSIL cases thus related to a reduced viral tumourigenicity (Refs 90-93).…”