BACKGROUND: Human papillomavirus (HPV) infection frequently induces hyperproliferation of epithelial cells, leading to both benign (warts) and malignant tumors (cervical cancer). We seek to understand how HPV may achieve these changes by modulating cellular population dynamics. Furthermore, HPV-induced lesion progression is generally understood as a series of molecular changes. As a complement to this approach, we investigate the role of phenotypic changes produced by natural selection during lesion progression. METHODS: We develop and numerically analyze spatially and evolutionarily explicit mathematical models of HPV-induced epithelial lesions. RESULTS: Infection of basal cells is a requirement for persistent infection. Increasing the maximum tissue density at which HPV-infected cells can divide and decreasing infected cell migration rate leads to large increases in the number of HPV-infected cells, and consequently, virions shed from the skin surface per day. Evolution by natural selection in an autonomous population of cells leads to tissue changes that are qualitatively similar to those observed during lesion progression. CONCLUSIONS: HPV modulates cell population dynamics, which can be characterized by specific ecological parameters. As an unintended consequence, this ecological strategy of the virus may be successfully co-opted by autonomous host cells and play a role in lesion progression.
BACKGROUND: Human papillomavirus (HPV) infection frequently induces hyperproliferation of epithelial cells, leading to both benign (warts) and malignant tumors (cervical cancer). We seek to understand how HPV may achieve these changes by modulating cellular population dynamics. Furthermore, HPV-induced lesion progression is generally understood as a series of molecular changes. As a complement to this approach, we investigate the role of phenotypic changes produced by natural selection during lesion progression. METHODS: We develop and numerically analyze spatially and evolutionarily explicit mathematical models of HPV-induced epithelial lesions. RESULTS:Infection of basal cells is a requirement for persistent infection. Increasing the maximum tissue density at which HPV-infected cells can divide and decreasing infected cell migration rate leads to large increases in the number of HPV-infected cells, and consequently, virions shed from the skin surface per day. Evolution by natural selection in an autonomous population of cells leads to tissue changes that are qualitatively similar to those observed during lesion progression. CONCLUSIONS:HPV modulates cell population dynamics, which can be characterized by specific ecological parameters. As an unintended consequence, this ecological strategy of the virus may be successfully co-opted by autonomous host cells and play a role in lesion progression.
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Keywords:
human papillomavirus; partial differential equation model; somatic evolution