The Subcellular Localisation of the Human Papillomavirus (HPV) 16 E7 Protein in Cervical Cancer Cells and Its Perturbation by RNA Aptamers.

Özlem Cesur,Jamel Mankouri,Nicola Stonehouse,George Blair,Helen Groves,Clare Nicol

doi:10.3390/v7072780

Özlem Cesur, Jamel Mankouri + Show 4 more

Open Access

https://doi.org/10.3390/v7072780

Copy DOI

Abstract

Human papillomavirus (HPV) is the most common viral infection of the reproductive tract, affecting both men and women. High-risk oncogenic types are responsible for almost 90% of anogenital and oropharyngeal cancers including cervical cancer. Some of the HPV “early” genes, particularly E6 and E7, are known to act as oncogenes that promote tumour growth and malignant transformation. Most notably, HPV-16 E7 interacts with the tumour suppressor protein pRb, promoting its degradation, leading to cell cycle dysregulation in infected cells. We have previously shown that an RNA aptamer (termed A2) selectively binds to HPV16 E7 and is able to induce apoptosis in HPV16-transformed cervical carcinoma cell lines (SiHa) through reduction of E7 levels. In this study, we investigated the effects of the A2 aptamer on E7 localisation in order to define its effects on E7 activity. We demonstrate for the first time that E7 localised to the plasma membrane. In addition, we show that A2 enhanced E7 localisation in the ER and that the A2-mediated reduction of E7 was not associated with proteasomal degradation. These data suggest that A2 perturbs normal E7 trafficking through promoting E7 ER retention.

Highlights

Papillomaviruses have been discovered in many vertebrates including humans, cattle, dogs, birds and reptiles
The Alpha genus contains high-risk mucosal Human papillomavirus (HPV) that are the main cause of cervical cancer [3]
We previously described an HPV16 E7 aptamer that resulted in a loss of E7 expression after transfection into HPV16+ cells [24]

Summary

Introduction

Papillomaviruses have been discovered in many vertebrates including humans, cattle, dogs, birds and reptiles. Human papillomaviruses (HPVs) are classified into five genera (Alpha, Beta, Gamma, Mu and Nu) [2]. The Alpha genus contains high-risk mucosal HPVs that are the main cause of cervical cancer [3]. Amongst high-risk genotypes, HPV16 and 18 are most frequently found in cervical biopsies [4]. The majority (70%–90%) of HPV infections with both high- and low-risk genotypes are asymptomatic and can be cleared spontaneously within one to two years. A small percentage of persistent infections (around ∼5%–10%) with high-risk types result in precancerous lesions. If untreated, these lesions may lead to squamous cell carcinoma (SCC) [5]

Objectives

Methods

Results

Conclusion