Quinlan Sarah, May Susan, Weeks Ryan, Yuan Hang, Luff Jennifer
Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
Department of Pathology, Georgetown University Medical Center, Washington, DC, United States.
Front Vet Sci. 2021 Mar 3;8:570982. doi: 10.3389/fvets.2021.570982. eCollection 2021.
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.
皮肤乳头瘤病毒是致癌病毒，可导致严重的持续性感染，在免疫缺陷个体（如患有X连锁重症联合免疫缺陷病（XSCID）的个体）暴露于紫外线（UV）的皮肤中可发展为皮肤癌。XSCID的犬类研究模型表现出类似的表型；这些犬会发生严重的犬乳头瘤病毒2型（CPV2）感染，且常进展为癌症。因此，犬是研究免疫缺陷患者皮肤乳头瘤病毒感染的天然自发模型。人乳头瘤病毒癌基因E6促进癌症发展，部分原因是启动肿瘤抑制蛋白p53的降解，或抑制细胞生长停滞和凋亡途径中所需的p53依赖性基因的上调，从而导致肿瘤发生所需的DNA损伤积累。目前，人们对CPV2及其促进癌症发展的机制知之甚少。本研究的目的是确定CPV2癌基因E6在紫外线辐射激活后是否同样影响p53，以及控制生长停滞和凋亡所需的下游p53调控基因。我们确定皮肤CPV2 E6不会降解p53，也不会干扰p53调控基因p21、Bax、Bak或lncRNA-p21的上调，这表明CPV2可能使用一种不依赖p53的机制促进肿瘤发生。
