Complete genome sequence of a HPV31 isolate from laryngeal squamous cell carcinoma and biological consequences for p97 promoter activity.

Yuri Munsamy,Riaz Y Seedat,Phillip A Bester,Tumelo R Sekee,Felicity J Burt,Maria Lina Tornesello

doi:10.1371/journal.pone.0252524

Abstract

Human papillomavirus type 31, although detected less frequently than HPV types 16 and 18, is associated with head and neck squamous cell carcinomas. Previous studies suggest that polymorphisms in the long control region (LCR) may alter the oncogenic potential of the virus. This study reports the first complete genome of a South African HPV31 isolate from a laryngeal squamous cell carcinoma. Sequence variations relative to the HPV31 prototype sequence were identified. The pBlue-Topo® vector, a reporter gene system was used to investigate the possible influence of these variations on the LCR promoter activity in vitro. Using mutagenesis to create two different fragments, β-galactosidase assays were used to monitor the effect of nucleotide variations on the p97 promoter. Increased β-galactosidase expression was observed in mutants when compared to the South African HPV31 LCR isolate. Enhanced transcriptional activity was observed with the mutant that possessed a single nucleotide change within the YY1 transcription factor binding site. In conclusion, sequence variation within the LCR of HPV31 isolates may have a functional effect on viral p97 promoter activity.

Highlights

Human papillomaviruses (HPVs) include over 200 different types and infection by one of the 13 high-risk types increases the risk of developing cervical, anogenital, or head and neck carcinomas (HNSCCs) [1, 2]
To determine the genetic relationship of the South African isolate and all available complete HPV31 genomes from cervical cancer from other parts of the world submitted previously to GenBank, a phylogenetic tree was constructed using Geneious version 2019.0 and classified to lineages according to Chen et al [15]. (Accession numbers for 29 isolates from cervical carcinomas retrieved from GenBank are available in S2 Table)
Sublineage A2 included HPV31 isolates with sequences closely related to the sequence of an isolate from cervical carcinoma from Thailand

Summary

Introduction

Human papillomaviruses (HPVs) include over 200 different types and infection by one of the 13 high-risk types increases the risk of developing cervical, anogenital, or head and neck carcinomas (HNSCCs) [1, 2]. These small double-stranded circular DNA viruses of approximately 8 000 base pairs (bp) contain between eight to nine open reading frames (ORFs) [3]. The E6 and E7 genes encode the HPV oncoproteins that promote cell cycle progression and viral DNA replication [3]. HPV types are distinguished by a genetic difference of around 10% in the L1 gene sequence of the genome [2].

Methods

Results

Discussion

Conclusion