Canine Papillomavirus 2 E6 Does Not Interfere With UVB-Induced Upregulation of p53 and p53-Regulated Genes

Abstract

Cutaneous papillomaviruses are oncogenic viruses that cause severe, persistent infections that can develop into skin cancers within ultraviolet (UV)-exposed skin of immunodeficient individuals, such as those with X-linked severe combined immunodeficiency (XSCID). A canine research model of XSCID exhibits a similar phenotype; these dogs develop severe canine papillomavirus 2 (CPV2) infections that often progress to cancer. Thus, the dog is a natural, spontaneous model to investigate cutaneous papillomavirus infections in immunodeficient patients. The human papillomavirus oncogene E6 contributes to cancer development, in part, by initiating degradation of the tumor suppressor protein p53, or by inhibiting upregulation of p53-dependent genes required within the cell growth arrest and apoptotic pathways, thereby leading to an accumulation of DNA damage required for oncogenesis. Currently, little is known about CPV2, and how it promotes cancer development. The aim of this study was to determine if CPV2 oncogene E6 similarly affects p53 upon activation by UV radiation, as well as the downstream p53-regulated genes necessary to control growth arrest and apoptosis. We determined that cutaneous CPV2 E6 does not degrade p53, or interfere with the upregulation of p53-regulated genes p21, Bax, Bak, or lncRNA-p21, suggesting that CPV2 may use a p53-independent mechanism to contribute to oncogenesis.

Pathological Similarities in the Development of Papillomavirus-Associated Cancer in Humans, Dogs, and Cats

“…However, the oncogenic mechanism of CfPV2 E6 might not be related to the well-described ability of E6 to degrade p53. Quinlan et al [ 49 ] reported that keratinocytes that expressed CfPV2 E6 exposed to UV did not decrease p53 levels nor avoid the expression of p21, B cell lymphoma (BCL)2 antagonist/killer (Bak), and Bcl-2-associated X (Bax). These results suggest that other p53-independent oncogenic undetermined mechanisms might be present in the malignity of E6 in dogs.…”