The biology and life-cycle of human papillomaviruses.

Human papillomaviruses (HPVs) have evolved over millions of years to propagate themselves in a range of different animal species including humans. Viruses that have co-evolved slowly in this way typically cause chronic inapparent infections, with virion production in the absence of apparent disease. This is the case for many Beta and Gamma HPV types. The Alpha papillomavirus types have however evolved immunoevasion strategies that allow them to cause persistent visible papillomas. These viruses activate the cell cycle as the infected epithelial cell differentiates in order to create a replication competent environment that allows viral genome amplification and packaging into infectious particles. This is mediated by the viral E6, E7, and E5 proteins. High-risk E6 and E7 proteins differ from their low-risk counterparts however in being able to drive cell cycle entry in the upper epithelial layers and also to stimulate cell proliferation in the basal and parabasal layers. Deregulated expression of these cell cycle regulators underlies neoplasia and the eventual progression to cancer in individuals who cannot resolve high-risk HPV infection. Most work to date has focused on the study of high-risk HPV types such as HPV 16 and 18, which has led to an understanding of the molecular pathways subverted by these viruses. Such approaches will lead to the development of better strategies for disease treatment, including targeted antivirals and immunotherapeutics. Priorities are now focused toward understanding HPV neoplasias at sites other than the cervix (e.g. tonsils, other transformation zones) and toward understanding the mechanisms by which low-risk HPV types can sometimes give rise to papillomatosis and under certain situations even cancers.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/rmv.1822

Human papillomavirus molecular biology and disease association

The papillomavirus E7 proteins.

Epigenetic reprogramming of host genes in viral and microbial pathogenesis

https://www.rug.nl/research/pathology/medbiol/pdf/ecadherin.pdf

E-cadherin: gatekeeper of airway mucosa and allergic sensitization

A common feature shared between several human cancer-associated viruses, such as Epstein-Barr virus, Hepatitis B virus and Hepatitis C virus, and Human papillomavirus (HPV) is the ability to reduce the expression of cellular E-cadherin. Since E-cadherin is used by Langerhans cells to move through the stratified epithelium, its reduction may affect the efficiency by which the immune system responds to HPV infection and the length of persistent HPV infections. We observed that the E7 protein of this virus (HPV16) is most efficient at reducing E-cadherin levels. This E7 activity is independent of retinoblastoma protein or AP-2α degradation. Instead it is associated with augmentation of cellular DNA methyltransferase I (Dnmt1) activity. Significantly, inhibition of Dnmt activity re-established E-cadherin levels of the cells, presenting the possibility that similar epigenetic intervention clinically may be a way to re-establish the influx of Langerhans cells into infected epithelium to counteract HPV persistence.

/pdf/epigenetic-repression-of-e-cadherin-by-human-papillomavirus-2clxx1rril.pdf

Epigenetic repression of E-cadherin by human papillomavirus 16 E7 protein.

PURPOSE The target cells for radiation carcinogenesis are widely held to be stem or stem-like cells. Classically, stem cells are considered to be those capable of renewing tissues while differentiated cells lose the potential to replicate. More recently it has become apparent that greater developmental plasticity exists and that cells can be reprogrammed to form induced pluripotent stem cells. Modelling of radiation cancer-risk requires understanding of the characteristics, numbers and responses of target stem cells to radiation. Therefore progress in understanding mechanisms of radiation-induced carcinogenesis is dependent on knowledge of stem cell radiobiology. RESULTS In this context, the European Community's network of excellence on low dose radiation risk called, 'Low Dose Research towards Multidisciplinary Integration (DoReMi)' ( www.doremi-noe.net ) and the United Kingdom's Health Protection Agency organised a workshop on Stem Cells and DNA damage in Oxfordshire on 7/8 December 2011 to address issues relating to radiation, DNA damage and stem cells. In keeping with the aim of improving understanding of low dose ionising radiation health risk, a panel of experts in stem cells and radiobiology were invited to this workshop. This summary includes all presentations at this workshop and is accompanied by full reports of several speakers.

Kenneth Raj

Papers

Epigenetic repression of E-cadherin by human papillomavirus 16 E7 protein.

DoReMi stem cells and DNA damage workshop. Introduction.