The human papillomavirus type 8 E2 protein suppresses beta4-integrin expression in primary human keratinocytes

Journal of Virology
Monika OldakSigrun Smola-Hess

Abstract

Human papillomaviruses (HPVs) infect keratinocytes of skin and mucosa. Homeostasis of these constantly renewing, stratified epithelia is maintained by balanced keratinocyte proliferation and terminal differentiation. Instructions from the extracellular matrix engaging integrins strongly regulate these keratinocyte functions. The papillomavirus life cycle parallels the differentiation program of stratified epithelia, and viral progeny is produced only in terminally differentiating keratinocytes. Whereas papillomavirus oncoproteins can inhibit keratinocyte differentiation, the viral transcription factor E2 seems to counterbalance the impact of oncoproteins. In this study we show that high expression of HPV type 8 (HPV8) E2 in cultured primary keratinocytes leads to strong down-regulation of beta4-integrin expression levels, partial reduction of beta1-integrin, and detachment of transfected keratinocytes from underlying structures. Unlike HPV18 E2-expressing keratinocytes, HPV8 E2 transfectants did not primarily undergo apoptosis. HPV8 E2 partially suppressed beta4-integrin promoter activity by binding to a specific E2 binding site leading to displacement of at least one cellular DNA binding factor. To our knowledge, we show for t...Continue Reading

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Citations

Jun 3, 2009·Microbiology and Molecular Biology Reviews : MMBR·Maciej LazarczykMichel Favre
Apr 11, 2008·The Journal of Investigative Dermatology·Regina PfefferleHerbert Pfister
Dec 20, 2005·The Journal of Pathology·Baki AkgülAlan Storey
Apr 9, 2019·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Assunta VenutiSigrun Smola
Mar 1, 2005·Cancer Research·Inke Diana SchaperHerbert Pfister
Jan 22, 2021·Journal of Virology·Frank StubenrauchRichard B S Roden
Jul 16, 2013·Virology·Alison A McBride

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