Biomedical Sciences ETDs

Publication Date

12-1-2014

Abstract

HPV16 infection evidently occurs within wounded epithelial tissue, but the cellular and molecular events that culminate in infection establishment remain poorly understood. While HPV is exposed to a multitude of cells in the wound environment, only hyperproliferative keratinocytes are believed to support productive infection. Keratinocytes acquire mobility during wound repair by undergoing prominent phenotypic alterations through an epithelial-to-mesenchymal transition (EMT). In this study, cell- and tissue-based models were employed to characterize HPV infection during epithelial wound healing, using both physical injury and growth factor treatment to induce keratinocyte migration. In a tissue-based model of wounding and infection using NIKS-derived organotypic raft' culture, HPV infection did not occur without epithelial wounding, consistent with animal models of wounding and HPV16 infection. Using cell monolayer, keratinocytes induced into an EMT were evaluated for their ability to support HPV16 early infection, which encompasses viral binding, entry, trafficking and nuclear delivery of encapsidated genes. It was found that keratinocytes in an EMT allowed reduced levels of virions to bind the cell surface but HPV16 infection was not supported. A subset of HPV virions appeared to enter cells during EMT, indicating that infection may be compromised post-entry. Interestingly, HPV16 infection of keratinocytes induced into EMT resumed coincident with the return of epithelial characteristics. So while an initial refractory period to infection exists in cells undergoing an EMT, HPV16 infects migrating cells during later stages of wound healing. Based on these results, migrating keratinocytes may serve as an additional reservoir of cellular HPV infection not previously identified.

Keywords

HPV16, Wound Healing

Document Type

Thesis

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Masters

Department Name

Biomedical Sciences Graduate Program

First Advisor

Ozbun, Michelle

First Committee Member (Chair)

Chackerian, Bryce

Second Committee Member

Hudson, Laurie

Third Committee Member

Peabody, David

Share

COinS