The Cellular Regulation of HPV Infection and Neoplasia

Friday 1 December 2017, 1.00PM

Speaker(s): Professor John Doorbar, Department of Pathology, University of Cambridge

The long co-evolution of papillomaviruses with their hosts underlies the fact that most PV types are associated with only self-limiting benign epithelial disease, or with subclinical infections.  Indeed, papillomaviruses have become epithelial specialists, with the 200 or so human types generally showing specific epithelial tropisms, and/or life cycle adaptations that reflect their different modes of transmission.

Whether an infection leads to a low-grade productive infection or to an abortive or ‘transforming’ infection depends on the subversion of normal functions that the virus requires to colonize the epithelium and to produce infectious particles.  The E6 and E7 genes are found in the vast majority of Human Papillomaviruses, but function as oncogenes only in particular HPV types and particular settings.  The regulation of viral gene expression at vulnerable epithelial sites such as the cervix, and the disruption of epithelial regulatory pathways at these sites now needs to be considered alongside high and low-risk HPV protein functions.

The regulation of epithelial homoeostasis, and the specific requirements of the cervical transformation zone where the majority of HPV-associated cancers arise, will be discussed in the context of HPV life-cycle regulation, and the ability of papillomaviruses to persist in the epithelial basal layer following infection. Although poorly understood, the successful immune control of infection is the usual outcome and can lead to latent infection and reactivation.  The application of this knowledge has allowed the development of disease stratification markers for diagnosis, and in the future we hope, to the development of antiviral approaches that might improve treatment.

More details on Professor John Doorbar, University of Cambridge

The host for this seminar is Professor Charles Lacey 

Location: K018

Email: cii@york.ac.uk

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