BACKGROUND During severe immunosuppression or treatment with specific biological drugs, human polyomavirus JC (JCPyV) may establish a lytic infection in oligodendrocytes, leading to progressive multifocal leukoencephalopathy (PML). Beyond AIDS, which represents the most common predisposing condition, several biological drugs have been associated to the development of PML, such as natalizumab, fingolimod and dimethyl fumarate, which have been showed to increase the risk of PML in the multiple sclerosis (MS) population. JCPyV non-coding control region (NCCR) can be found in two different forms: a virulent neurotropic pathogenic form and a latent non-pathogenic form. The neurotropic forms contain a rearranged NCCR and are typically found in the cerebrospinal fluid, brain or blood of PML patients. CASE PRESENTATION We sequenced and critically examined JCPyV NCCR from isolates detected in the cerebrospinal fluid of four newly diagnosed progressive multifocal leukoencephalopathy patients: two HIV-positive and two HIV-negative multiple sclerosis patients. More complex NCCR rearrangements were observed in the two HIV-positive patients compared to the HIV-negative multiple sclerosis patients with PML. CONCLUSIONS The comparison of HIV-positive and HIV-negative MS patients with PML, allowed us to evidence the presence of a common pattern of JCPyV NCCR rearrangement, characterized by the deletion of the D-block, which could be one of the initial rearrangements of JCPyV NCCR needed for the development of PML.

中文翻译：

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在具有不同危险因素的PML患者中进行JCPyV NCCR分析：探索常见的重排，将其作为神经病变的重要改变。

背景技术在严重的免疫抑制或特定生物药物治疗期间，人多瘤病毒JC（JCPyV）可能在少突胶质细胞中建立溶菌感染，导致进行性多灶性白质脑病（PML）。除了代表最常见易感病的艾滋病外，几种生物药物也与PML的发展有关，如那他珠单抗，芬戈莫德和富马酸二甲酯，它们已被证明会增加多发性硬化症（MS）人群中PML的风险。 。JCPyV非编码控制区（NCCR）可以两种不同的形式发现：有毒的神经致病性形式和潜在的非致病性形式。趋神经形式含有重排的NCCR，通常在PML患者的脑脊液，脑或血液中发现。病例介绍我们对4例新诊断的进行性多灶性白质脑病患者在脑脊液中检测到的分离株进行了JCPyV NCCR测序，并进行了严格检查：2例HIV阳性和2例HIV阴性的多发性硬化症患者。与两名携带PML的HIV阴性多发性硬化症患者相比，在两名HIV阳性患者中观察到了更为复杂的NCCR重排。结论通过比较HIV阳性和HIV阴性的MS患者与PML，我们可以证明存在JCPyV NCCR重排的常见模式，其特征是缺失了D阻滞，这可能是DCP的最初重排之一。 PML的开发需要JCPyV NCCR。两名HIV阳性和两名HIV阴性多发性硬化症患者。与两名携带PML的HIV阴性多发性硬化症患者相比，在两名HIV阳性患者中观察到了更为复杂的NCCR重排。结论通过比较HIV阳性和HIV阴性的MS患者与PML，我们可以证明存在JCPyV NCCR重排的常见模式，其特征是缺失了D阻滞，这可能是DCP的最初重排之一。 PML的开发需要JCPyV NCCR。两名HIV阳性和两名HIV阴性多发性硬化症患者。与两名携带PML的HIV阴性多发性硬化症患者相比，在两名HIV阳性患者中观察到了更为复杂的NCCR重排。结论通过比较HIV阳性和HIV阴性的MS患者与PML，我们可以证明存在JCPyV NCCR重排的常见模式，其特征是缺失了D阻滞，这可能是DCP的最初重排之一。 PML的开发需要JCPyV NCCR。