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首页> 外文期刊>PLoS Pathogens >High expression of JC polyomavirus-encoded microRNAs in progressive multifocal leukoencephalopathy tissues and its repressive role in virus replication
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High expression of JC polyomavirus-encoded microRNAs in progressive multifocal leukoencephalopathy tissues and its repressive role in virus replication

机译：渐进式多焦点白血病组织中JC多瘤病毒编码的微大疱疹的高表达及其在病毒复制中的抑制作用

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摘要

JC polyomavirus (JCPyV, JCV) causes progressive multifocal leukoencephalopathy (PML) in immunocompromised hosts. JCPyV replicates in oligodendrocytes within the brain tissue of patients with PML. The JCPyV genome encodes a microRNA (miRNA) in the region encoding the large T antigen. JCPyV-encoded miRNA (miR-J1) has been detected in the tissue and cerebrospinal fluid samples of patients with PML; however, there are no reports describing the localization of polyomavirus-encoded miRNA in histological samples of patients with virus-associated diseases. In the present study, we detected high miR-J1 expression in the nuclei of JCPyV-infected cells in PML tissue samples via in situ hybridization. Additionally, in situ hybridization also revealed the expression of BK polyomavirus (BKPyV, BKV)-encoded miRNA in lesions of BKPyV-associated nephropathy. In situ hybridization for miR-J1-5p and -3p showed positive signals in 24/25 (96%) of PML tissues that were positive for JCPyV by immunohistochemistry. Higher copy numbers of miR-J1 were detected in PML tissues than in non-PML tissues by real-time reverse transcription PCR. Next generation sequencing showed that miR-J1-5p, a mature miRNA of primary miRNA, was predominant in the lesions compared with miR-J1-3p, another mature miRNA. Deletion or mutation of miR-J1 in recombinant JCPyV promoted the production of JCPyV-encoded proteins in cells transfected with JCPyV DNA, suggesting that polyomavirus-encoded miRNA may have a repressive role in viral replication in PML tissues. In situ hybridization for viral miRNA may be a useful diagnostic tool for PML.
机译：JC PolyomaVirus（JCPYV，JCV）导致免疫功能性宿主中的逐步多焦点白血病（PML）。 JCPYV在PML患者脑组织内的oligodendrocytes中重复。 JCPYV基因组在编码大T抗原的区域中编码微小RORNA（miRNA）。在PML患者的组织和脑脊液样本中检测到JCPYV编码的miRNA（miR-J1）;然而，没有关于病毒 - 相关疾病患者组织学样本中多瘤病毒编码的miRNA的定位的报道。在本研究中，我们通过原位杂交检测在PML组织样品中的JCPYV感染细胞中的高miR-J1表达。另外，原位杂交也揭示了BKPyV-相关肾病的病变中BK多瘤（BkpyV，BKV）的表达。原位杂交MIR-J1-5P和-3P显示24/25（96％）的PML组织中的阳性信号，其通过免疫组织化学对JCPYV呈阳性。通过实时逆转录PCR在PML组织中检测到MIR-J1的较高拷贝数。下一代测序表明，与MiR-J1-3P相比，MiR-J1-5P，原发性miRNA的成熟miRNA是主要的损伤中的另一个成熟miRNA。重组JCPYV中MIR-J1的缺失或突变促进了用JCPYV DNA转染的细胞中JCPYV编码蛋白的产生，表明聚瘤病毒编码的miRNA可能对PML组织中的病毒复制中具有抑制作用。原位杂交用于病毒miRNA可以是PML的有用诊断工具。

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