Expression of the HPV11 E2 gene in transgenic mice does not result in alterations of the phenotypic pattern

Abstract

The E2 early protein of human papillomaviruses (HPV) has been found associated with the mitotic spindle therefore being implicated in the partition of the replicated viral DNA to daughter cells. In addition, E2 proteins bind to the upstream regulatory region of the virus and to cellular promoters modulating thereby cellular transcription and differentiation. In many cervical cancers, the E2 reading frame is interrupted upon incorporation of the viral genome into the host DNA. This results in the loss of the E2 mediated transcriptional repression and uncontrolled expression of the viral oncogenes. All these results have been obtained in transfected cells but no information is available on the E2 effects in the context of the entire organism. Transgenic mice were generated expressing the E2 protein of HPV11 under the control of the Ubiquitin C promoter. E2 mRNA is present in all mice tissues analysed and the E2 protein expressed in the skin (the target tissue of HPV11) was shown by Western blotting, albeit at a very low level. Analysis of the transgenic mice shows no major histological changes in the skin or all other tissues investigated. These data indicate that in transgenic mice the human papillomavirus type 11 E2 does not grossly modulate cellular proliferation or differentiation events.

The Human Papillomavirus Type 8 E2 Protein Induces Skin Tumors in Transgenic Mice

“…On the contrary, overexpression of genus-a HPV16-and HPV18-E2 results in cell-cycle arrest (Francis et al, 2000;Wells et al, 2000) and apoptosis (Desaintes et al, 1999;Webster et al, 2000) depending on the cell type and p53 status. HPV11-E2transgenic mice showed no histological changes in the skin (Leykauf et al, 2008). In contrast, skin tumor formation in HPV8-E2 mice here revealed an intrinsic oncogenic potential of a genus-b E2 protein in vivo.…”

Expression of Mitochondrial Non-coding RNAs (ncRNAs) Is Modulated by High Risk Human Papillomavirus (HPV) Oncogenes

“…Expression of the HPV-8 E2 gene in transgenic mice results in increased skin cancer development, which is enhanced by UV irradiation (41, 42). On the other hand, HPV-11 E2, a low risk HPV virus, does not induce cell transformation (43). Whether the induction of skin cancer is related to the ability of HPV-8 E2 to induce knockdown of the ASncmtRNAs warrants future research.…”

The Papillomavirus E2 proteins

“…Expression of the HPV8 E2 protein, but not HPV11 E2, in the skin of transgenic mice results in the development of skin tumors (Leykauf et al, 2008; Pfefferle et al, 2008). Furthermore, the development of these tumors is accelerated by exposure to UV radiation.…”