Pagliarulo, E;
(2014)
Understanding the Early Events of Human Papillomavirus Lesion Formation.
Doctoral thesis , UCL (University College London).
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Abstract
The events during papillomavirus lesion-formation are not well understood, but are likely to differ between high and low risk HPV types, which have different effects on the infected basal layer. These differences most likely reflect differences in protein function and gene expression patterns that have evolved to support the different biologies of the two virus groups. While high-risk types such asHPV16 or 18 can drive cell proliferation in the basal and suprabasal layers, low‐risk types such as HPV 6 and 11 appear not to require this function. In order to compare the two virus groups we have introduced the different HPV genomes into a genetically identical keratinocyte background and examined their effect on functions required for lesion formation following epithelial trauma. The non‐immortal keratinocyte cells have normal differentiation properties, are near‐diploid and are sensitive to contact inhibition. They are currently used in the clinic to prepare skin substitutes for burns victims. In this model, high-risk HPV types increase cell growth (but not migration) rate when cells have space to grow, such as would occur during wound healing. They can also overcome normal cell‐cell contact inhibition as the cells pack‐up, and this is manifest in organotypic rafts as an increase in basal and parabasal cell division similar to that seen in neoplasia. This growth advantage would allow a single infected cell to outgrow its uninfected neighbours following infection or during lesion expansion after wounding. Interestingly, the low‐risk HPV types appear to have negative effect on growth rate, allowing the more rapidly dividing uninfected cells to predominate. This suggests a fundamental difference in the biology of the two HPV groups, and supports the idea that low-risk types may reside in long‐lived slow-cycling cell such as stem cell. For the high-risk types this model may not hold true, with lesion‐formation being directed actively through functional changes in the infected basal layer.
| Type: | Thesis (Doctoral) |
|---|---|
| Title: | Understanding the Early Events of Human Papillomavirus Lesion Formation |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| UCL classification: | UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1443084 |
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