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Transcriptional regulation of genes involved in keratinocyte differentiation by human papillomavirus 16 oncoproteins

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Abstract

The life cycle of human papillomaviruses (HPVs) is strictly linked to the differentiation of their natural host cells. The HPV E6 and E7 oncoproteins can delay the normal differentiation program of keratinocytes; however, the exact mechanisms responsible for this have not yet been identified. The goal of this study was to investigate the effects of HPV16 oncoproteins on the expression of genes involved in keratinocyte differentiation. Primary human keratinocytes transduced by LXSN (control) retroviruses or virus vectors expressing HPV16 E6, E7 or E6/E7 genes were subjected to gene expression profiling. The results of microarray analysis showed that HPV 16 E6 and E7 have the capacity to downregulate the expression of several genes involved in keratinocyte differentiation. Quantitative real-time polymerase chain reaction (qRT-PCR) assays were performed to confirm the microarray data. To investigate the effects of the HPV oncoproteins on the promoters of selected keratinocyte differentiation genes, luciferase reporter assays were performed. Our results suggest that the HPV 16 E6 and/or E7 oncogenes are able to downregulate the expression of several genes involved in keratinocyte differentiation (such as desmocollin 1, keratin 4, S100 calcium-binding protein A8 and small proline-rich protein 1A), at least partially by downregulating their promoter activity. This activity of the HPV oncoproteins may have a role in the productive virus life cycle, and also in virus-induced carcinogenesis.

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Acknowledgments

The research of EG was supported by the European Union and the State of Hungary, co-financed by the European Social Found in the framework of TÁMOP 4.2.4.A/2-11-1-2012-0001 ‘National Excellence Program’. This study was supported by a grant from the Hungarian Scientific Research Fund (OTKA K 81422).

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Authors and Affiliations

  1. Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

    Eszter Gyöngyösi, Anita Szalmás, Annamária Ferenczi, József Kónya & György Veress

  2. Department of Biochemistry and Molecular Biology, Genomic Medicine and Bioinformatics Core Facility, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

    Szilárd Póliska

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  1. Eszter Gyöngyösi
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  2. Anita Szalmás
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  3. Annamária Ferenczi
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  4. Szilárd Póliska
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  5. József Kónya
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  6. György Veress
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Correspondence to György Veress.

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Gyöngyösi, E., Szalmás, A., Ferenczi, A. et al. Transcriptional regulation of genes involved in keratinocyte differentiation by human papillomavirus 16 oncoproteins. Arch Virol 160, 389–398 (2015). https://doi.org/10.1007/s00705-014-2305-y

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  • DOI: https://doi.org/10.1007/s00705-014-2305-y

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