Hermonat P L, Plott R T, Santin A D, Parham G P, Flick J T
Department of Obstetrics & Gynecology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Gynecol Oncol. 1997 Sep;66(3):487-94. doi: 10.1006/gyno.1997.4789.
Seroepidemiologic studies demonstrate that adeno-associated virus (AAV) infection is negatively associated with cervical cancer. This inverse association may be due to an ability of AAV to inhibit the role of human papillomavirus (HPV) in cervical carcinogenesis. In support of this hypothesis AAV has been demonstrated to inhibit several papillomavirus types, including bovine papillomavirus type 1 and human papillomaviruses types 16 and 18 (HPV-16/18) in tissue culture. The AAV-encoded Rep78 protein was responsible for this inhibition. These previous studies, however, were largely carried out in immortalized mouse fibroblasts. This cell type is likely not to be the most accurate model cell type for studying HPV-associated cervical carcinogenesis. In this study it is demonstrated that AAV Rep78 protein inhibits oncogenic transformation of freshly explanted primary human foreskin keratinocytes by an HPV-16/ras chimeric genome. Such cells are the natural host cell type for HPV-16/18 infection. It is also demonstrated that the HPV-16 P97 promoter is specifically inhibited by Rep78 in a transient CAT assay. These data further extend our knowledge of the AAV-papillomavirus interaction and provide a model for investigating the negative association of AAV with cervical cancer.
血清流行病学研究表明，腺相关病毒（AAV）感染与宫颈癌呈负相关。这种负相关可能是由于AAV具有抑制人乳头瘤病毒（HPV）在宫颈癌发生过程中作用的能力。支持这一假说的是，在组织培养中已证明AAV能抑制多种乳头瘤病毒类型，包括1型牛乳头瘤病毒以及16型和18型人乳头瘤病毒（HPV - 16/18）。AAV编码的Rep78蛋白负责这种抑制作用。然而，这些先前的研究大多是在永生化的小鼠成纤维细胞中进行的。这种细胞类型可能不是研究HPV相关宫颈癌发生最准确的模型细胞类型。在本研究中，证明了AAV Rep78蛋白通过HPV - 16/ras嵌合基因组抑制新鲜分离的原代人包皮角质形成细胞的致癌转化。此类细胞是HPV - 16/18感染的天然宿主细胞类型。还证明了在瞬时CAT测定中，Rep78能特异性抑制HPV - 16 P97启动子。这些数据进一步扩展了我们对AAV - 乳头瘤病毒相互作用的认识，并为研究AAV与宫颈癌的负相关提供了一个模型。
