Rencic A, Gordon J, Otte J, Curtis M, Kovatich A, Zoltick P, Khalili K, Andrews D
Molecular Neurovirology, Jefferson Institute of Molecular Medicine, Philadelphia, PA 19107, USA.
Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7352-7. doi: 10.1073/pnas.93.14.7352.
We describe molecular and clinical findings in an immunocompetent patient with an oligoastrocytoma and the concomitant presence of the human papovavirus, JC virus (JCV), which is the etiologic agent of the subacute, debilitating demyelinating disease, progressive multifocal leukoencephalopathy. Histologic review revealed a glial neoplasm consisting primarily of a moderately cellular oligodendroglioma with distinct areas of a fibrillary astrocytoma. Immunohistochemical analysis revealed nuclear staining of tumor cells with antibodies against the viral oncoprotein [tumor antigen (T antigen)], the proliferation marker (Ki67), and the cellular proliferation regulator (p53). Using primers specific to the JCV control region, PCR yielded amplified DNA that was identical to the control region of the Mad-4 strain of the virus. PCR analysis demonstrated the presence of the genome for the viral oncoprotein, T antigen, and results from primer extension studies revealed synthesis of the viral early RNA for T antigen in the tumor tissues. The presence of viral T antigen in the tumor tissue was further demonstrated by immunoblot assay. To our knowledge, this is the first report of the presence of JCV DNA, RNA, and T antigen in tissue in which viral T antigen is localized to tumor cell nuclei and suggests the possible association of JCV with some glial neoplasms.
我们描述了一名免疫功能正常的少突星形细胞瘤患者的分子和临床发现，该患者同时存在人乳头多瘤空泡病毒（JC病毒，JCV），它是亚急性、使人衰弱的脱髓鞘疾病——进行性多灶性白质脑病的病原体。组织学检查显示为一种胶质肿瘤，主要由细胞中度丰富的少突胶质细胞瘤以及明显的纤维型星形细胞瘤区域组成。免疫组化分析显示，针对病毒癌蛋白[肿瘤抗原（T抗原）]、增殖标志物（Ki67）和细胞增殖调节因子（p53）的抗体可使肿瘤细胞核染色。使用针对JCV控制区的特异性引物，PCR扩增出的DNA与该病毒Mad-4株的控制区相同。PCR分析证实了病毒癌蛋白T抗原基因组的存在，引物延伸研究结果显示肿瘤组织中合成了T抗原的病毒早期RNA。免疫印迹分析进一步证实了肿瘤组织中存在病毒T抗原。据我们所知，这是首次报道在肿瘤细胞核中检测到病毒T抗原的组织中存在JCV DNA、RNA和T抗原，提示JCV可能与某些胶质肿瘤有关。
