Department of Public Health and Infectious Diseases, "Sapienza" University of Rome, P.1e Aldo Moro, 5, 00185, Rome, Italy.
Laboratory of Microbiology of Chronic-Neurodegenerative Diseases, IRCCS San Raffaele Roma, Rome, Italy.
J Neurovirol. 2023 Apr;29(2):232-236. doi: 10.1007/s13365-023-01129-z. Epub 2023 Apr 25.
Due to its peculiar histopathological findings, pleomorphic xanthoastrocytoma (PXA), a rare cerebral tumor of young adults with a slow growth and a good prognosis, resembles to the lytic phase of progressive multifocal leukoencephalopathy, a fatal neurodegenerative disease caused by JC polyomavirus (JCPyV). Therefore, the presence of JCPyV DNA was examined in an 11-year-old child with xanthoastrocytoma, WHO grade 3, by quantitative PCR (qPCR) and nested PCR (nPCR) using primers amplifying sequences encoding the N- and C-terminal region of large T antigen (LTAg), the non-coding control region (NCCR), and viral protein 1 (VP1) DNA. The expression of transcripts from LTAg and VP1 genes was also evaluated. In addition, viral microRNAs' (miRNAs) expression was investigated. Cellular p53 was also searched at both DNA and RNA level. qPCR revealed the presence of JCPyV DNA with a mean value of 6.0 × 10 gEq/mL. nPCR gave a positive result for the 5' region of the LTAg gene and the NCCR, whereas 3' end LTAg and VP1 DNA sequences were not amplifiable. Only LTAg transcripts of 5' end were found whereas VP1 gene transcript was undetectable. Although in most cases, either Mad-1 or Mad-4 NCCRs have been identified in association with JCPyV-positive human brain neoplasms, the archetype NCCR structure was observed in the patient's sample. Neither viral miRNA miR-J1-5p nor p53 DNA and RNA were detected. Although the expression of LTAg supports the possible role of JCPyV in PXA, further studies are warranted to better understand whether the genesis of xanthoastrocytoma could depend on the transformation capacity of LTAg by Rb sequestration.
由于其独特的组织病理学发现,多形性黄色星形细胞瘤(PXA)是一种罕见的青年脑肿瘤,生长缓慢,预后良好,类似于进行性多灶性白质脑病的溶骨性阶段,这是一种由 JC 多瘤病毒(JCPyV)引起的致命神经退行性疾病。因此,通过定量 PCR(qPCR)和巢式 PCR(nPCR)使用扩增编码大 T 抗原(LTAg)N 和 C 末端区域、非编码控制区(NCCR)和病毒蛋白 1(VP1)DNA 的引物,检查了一名 11 岁患有 3 级黄色星形细胞瘤的儿童的 JCPyV DNA。还评估了 LTAg 和 VP1 基因转录本的表达。此外,还研究了病毒 microRNAs(miRNAs)的表达。还在 DNA 和 RNA 水平上搜索了细胞 p53。qPCR 显示 JCPyV DNA 的存在,平均值为 6.0×10 gEq/mL。nPCR 对 LTAg 基因 5' 端和 NCCR 给出了阳性结果,而 3' 端 LTAg 和 VP1 DNA 序列不可扩增。仅发现 5' 端的 LTAg 转录本,而 VP1 基因转录本不可检测。尽管在大多数情况下,与 JCPyV 阳性人脑肿瘤相关的 Mad-1 或 Mad-4 NCCR 已被识别,但在患者样本中观察到原型 NCCR 结构。既没有检测到病毒 miRNA miR-J1-5p,也没有检测到 p53 DNA 和 RNA。尽管 LTAg 的表达支持 JCPyV 在 PXA 中的可能作用,但需要进一步的研究来更好地理解黄色星形细胞瘤的发生是否取决于 LTAg 通过 Rb 隔离的转化能力。