ArticleJournal of virology2004
The human papillomavirus type 8 E2 protein suppresses beta4-integrin expression in primary human keratinocytes.
Article in Journal of virology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 40 citations in OpenAlex.
- RNA-seq analysis of host and viral gene expression highlights interaction between varicella zoster virus and keratinocyte differentiation.PLoS pathogens · 2014Trial
- Epidemiology, Molecular Pathogenesis, Immuno-Pathogenesis, Immune Escape Mechanisms and Vaccine Evaluation for HPV-Associated Carcinogenesis.Pathogens (Basel, Switzerland) · 2023Review
- EXPRESSION OF E8^E2 IS REQUIRED FOR WART FORMATION BY MOUSE PAPILLOMAVIRUS 1 IN VIVO.Journal of virology · 2021Article
- Human papillomavirus type 38 alters wild-type p53 activity to promote cell proliferation via the downregulation of integrin alpha 1 expression.PLoS pathogens · 2020Article
- Cross-talk of cutaneous beta human papillomaviruses and the immune system: determinants of disease penetrance.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019Review
- Chronic Inflammatory Microenvironment in Epidermodysplasia Verruciformis Skin Lesions: Role of the Synergism Between HPV8 E2 and C/EBPβ to Induce Pro-Inflammatory S100A8/A9 Proteins.Frontiers in microbiology · 2018Article
- The papillomavirus E2 proteins.Virology · 2013Review
- Identification and analysis of papillomavirus E2 protein binding sites in the human genome.Journal of virology · 2012Article
- Human papillomavirus type 8 interferes with a novel C/EBPβ-mediated mechanism of keratinocyte CCL20 chemokine expression and Langerhans cell migration.PLoS pathogens · 2012Article
- The HPV E2-Host Protein-Protein Interactions: A Complex Hijacking of the Cellular Network.The open virology journal · 2012Article
- HPV16 E2 could act as down-regulator in cellular genes implicated in apoptosis, proliferation and cell differentiation.Virology journal · 2011Article
- The E2 protein of human papillomavirus type 8 increases the expression of matrix metalloproteinase-9 in human keratinocytes and organotypic skin cultures.Medical microbiology and immunology · 2011Article
- Differential regulation of human papillomavirus type 8 by interferon regulatory factors 3 and 7.Journal of virology · 2011Article
- Interaction of the papillomavirus E8--E2C protein with the cellular CHD6 protein contributes to transcriptional repression.Journal of virology · 2010Article
- Human papillomavirus type 8 E2 protein unravels JunB/Fra-1 as an activator of the beta4-integrin gene in human keratinocytes.Journal of virology · 2010Article
- The EVER proteins as a natural barrier against papillomaviruses: a new insight into the pathogenesis of human papillomavirus infections.Microbiology and molecular biology reviews : MMBR · 2009Review
- Human papillomavirus type 16 E2 protein transcriptionally activates the promoter of a key cellular splicing factor, SF2/ASF.Journal of virology · 2009Article
- Expression of the HPV11 E2 gene in transgenic mice does not result in alterations of the phenotypic pattern.Transgenic research · 2008Article
- Functional divergence of Kaposi's sarcoma-associated herpesvirus and related gamma-2 herpesvirus thymidine kinases: novel cytoplasmic phosphoproteins that alter cellular morphology and disrupt adhesion.Journal of virology · 2005Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
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 the first time that specific E2 binding contributes to regulation of a cellular promoter. In vivo, decreased beta4-integrin expression is associated with detachment of keratinocytes from the underlying basement membrane and their egress from the basal to suprabasal layers. In papillomavirus disease, beta4-integrin down-regulation in keratinocytes with higher E2 expression may push virally infected cells into the transit-amplifying compartment and ensure their commitment to the differentiation process required for virus replication.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.