Transcriptional control and cell type specificity of HPV gene expression

Abstract

Background: Papillomaviruses are of great medical interest as they are causally associated with benign and malignant neoplasia of mucosal and cutaneous epithelia. The viral genome can be viewed as a control unit that releases signals in form of transforming proteins in infected epithelial cells. These proteins create a molecular environment favorable for papillomavirus biology and an expanded cell population for multiplication of the virus. On the other side, the genome receives signals through cellular transcription factors. Observations: Cellular transcription factors help the virus to identify the epithelial target cell, and they provide information about mitotic and physiologic signals to the epithelium and its differentiation state. Present research concentrates on the question how these distinct functions are brought about by factors that are ubiquitous rather than cell-type specific, such as NFI/CTF, TEF-1, AP-1, oct-1, and the progesterone receptor. Papillomaviruses have the additional capability to generate positive and negative feedback loops of gene expression through the virally encoded E2 proteins, a necessary tool to achieve long-term persistence. Conclusions: An intricate interplay between cellular and viral transcription factors is a prerequisite for epithelial specificity, physiologic responses, and persistence of papillomavirus infections.