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Virology Journal
Published in: Virology Journal 1/2011

Open Access 01-12-2011 | Research

HPV16 E2 could act as down-regulator in cellular genes implicated in apoptosis, proliferation and cell differentiation

Authors: Eric Ramírez-Salazar, Federico Centeno, Karen Nieto, Armando Valencia-Hernández, Mauricio Salcedo, Efraín Garrido

Published in: Virology Journal | Issue 1/2011

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Abstract

Background

Human Papillomavirus (HPV) E2 plays several important roles in the viral cycle, including the transcriptional regulation of the oncogenes E6 and E7, the regulation of the viral genome replication by its association with E1 helicase and participates in the viral genome segregation during mitosis by its association with the cellular protein Brd4. It has been shown that E2 protein can regulate negative or positively the activity of several cellular promoters, although the precise mechanism of this regulation is uncertain. In this work we constructed a recombinant adenoviral vector to overexpress HPV16 E2 and evaluated the global pattern of biological processes regulated by E2 using microarrays expression analysis.

Results

The gene expression profile was strongly modified in cells expressing HPV16 E2, finding 1048 down-regulated genes, and 581 up-regulated. The main cellular pathway modified was WNT since we found 28 genes down-regulated and 15 up-regulated. Interestingly, this pathway is a convergence point for regulating the expression of genes involved in several cellular processes, including apoptosis, proliferation and cell differentiation; MYCN, JAG1 and MAPK13 genes were selected to validate by RT-qPCR the microarray data as these genes in an altered level of expression, modify very important cellular processes. Additionally, we found that a large number of genes from pathways such as PDGF, angiogenesis and cytokines and chemokines mediated inflammation, were also modified in their expression.

Conclusions

Our results demonstrate that HPV16 E2 has regulatory effects on cellular gene expression in HPV negative cells, independent of the other HPV proteins, and the gene profile observed indicates that these effects could be mediated by interactions with cellular proteins. The cellular processes affected suggest that E2 expression leads to the cells in to a convenient environment for a replicative cycle of the virus.
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Metadata
Title
HPV16 E2 could act as down-regulator in cellular genes implicated in apoptosis, proliferation and cell differentiation
Authors
Eric Ramírez-Salazar
Federico Centeno
Karen Nieto
Armando Valencia-Hernández
Mauricio Salcedo
Efraín Garrido
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2011
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/1743-422X-8-247

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