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01-07-2019 | Human Papillomavirus | Original Article

Intratype variants of the E2 protein from human papillomavirus type 18 induce different gene expression profiles associated with apoptosis and cell proliferation

Authors: Alma Mariana Fuentes-González, J. Omar Muñoz-Bello, Joaquín Manzo-Merino, Adriana Contreras-Paredes, Abraham Pedroza-Torres, Jorge Fernández-Retana, Carlos Pérez-Plasencia, Marcela Lizano

Published in: Archives of Virology | Issue 7/2019

Abstract

Persistent infections with high-risk human papillomaviruses (HR-HPVs) are linked to the development of cervical cancer due to a deregulation of the productive viral cycle in the host cell, leading to cell transformation. The E2 viral protein is expressed early during an HPV infection and regulates viral replication and transcription. Other functions have been attributed to E2, such as the promotion of apoptosis that are independent of its role in the regulation of the expression of E6 and E7 viral oncogenes. Moreover, it has been shown that the HPV16 E2 protein has regulatory effects on cellular gene expression, suggesting that it participates in the modulation of different cellular processes. Intratype genomic variations within high-risk HPV types have an impact on the prognosis of HPV-related lesions. Nevertheless, the biological significance of HPV18 E2 intratype variations has not been analysed previously. The aim of this study was to determine whether HPV18 E2 intratype variations differentially modulate gene expression and whether cell-death-related genes are affected by variations in E2. We demonstrate that HPV18 E2 intratype Asian Amerindian (AsAi) and African (Af) variants differentially affect gene expression profiles. Although the E2-AsAi variant was found to modulate a larger number of cellular genes, both E2 variants affected similar cellular processes. Nevertheless, E2-AsAi and E2-Af variants showed differences in their ability to induce apoptosis, where E2-Af had a stronger effect. The differences in gene expression profiles in cells harbouring E2 intratype variants suggest a possible effect on diverse cellular signalling pathways, and this might suggest an approach for identifying biological processes regulated by HPV18 E2 intratype variants.

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Title: Intratype variants of the E2 protein from human papillomavirus type 18 induce different gene expression profiles associated with apoptosis and cell proliferation
Authors: Alma Mariana Fuentes-González
J. Omar Muñoz-Bello
Joaquín Manzo-Merino
Adriana Contreras-Paredes
Abraham Pedroza-Torres
Jorge Fernández-Retana
Carlos Pérez-Plasencia
Marcela Lizano
Publication date: 01-07-2019
Publisher: Springer Vienna
Keyword: Human Papillomavirus
Published in: Archives of Virology / Issue 7/2019
Print ISSN: 0304-8608
Electronic ISSN: 1432-8798
DOI: https://doi.org/10.1007/s00705-018-04124-6

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