Prezioso Carla, Pietropaolo Valeria, Moens Ugo, Ciotti Marco
Department of Public Health and Infectious Diseases, "Sapienza" University of Rome Rome, Italy.
IRCSS San Raffaele Roma, Microbiology of Chronic Neuro-Degenerative Pathologies Rome, Italy.
Expert Rev Mol Diagn. 2023 Feb;23(2):143-157. doi: 10.1080/14737159.2023.2179394. Epub 2023 Feb 17.
JC polyomavirus is the causative agent of progressive multifocal leukoencephalopathy (PML), a demyelinating disease resulting from the lytic infection of oligodendrocytes that may develop in immunosuppressed individuals: HIV1 infected or individuals under immunosuppressive therapies. Understanding the biology of JCPyV is necessary for a proper patient management, the development of diagnostic tests, and risk stratification.
The review covers different areas of expertise including the genomic characterization of JCPyV strains detected in different body compartments (urine, plasma, and cerebrospinal fluid) of PML patients, viral mutations, molecular diagnostics, viral miRNAs, and disease.
The implementation of molecular biology techniques improved our understanding of JCPyV biology. Deep sequencing analysis of viral genomes revealed the presence of viral quasispecies in the cerebrospinal fluid of PML patients characterized by noncoding control region rearrangements and VP1 mutations. These neurotropic JCPyV variants present enhanced replication and an altered cell tropism that contribute to PML development. Monitoring these variants may be relevant for the identification of patients at risk of PML. Multiplex realtime PCR targeting both the and the archetype NCCR could be used to identify them. Failure to amplify NCCR should indicate the presence of a JCPyV prototype speeding up the diagnostic process.
JC多瘤病毒是进行性多灶性白质脑病(PML)的病原体,这是一种由少突胶质细胞溶解性感染引起的脱髓鞘疾病,可能发生在免疫抑制个体中:感染HIV-1的个体或接受免疫抑制治疗的个体。了解JCPyV的生物学特性对于正确的患者管理、诊断测试的开发和风险分层是必要的。
本综述涵盖了不同的专业领域,包括在PML患者不同身体部位(尿液、血浆和脑脊液)检测到的JCPyV毒株的基因组特征、病毒突变、分子诊断、病毒微小RNA和疾病。
分子生物学技术的应用提高了我们对JCPyV生物学的理解。对病毒基因组的深度测序分析揭示了PML患者脑脊液中存在病毒准种,其特征为非编码控制区重排和VP1突变。这些嗜神经JCPyV变体具有增强的复制能力和改变的细胞嗜性,这有助于PML的发展。监测这些变体可能与识别有PML风险的患者有关。针对野生型和原型NCCR的多重实时PCR可用于识别它们。未能扩增NCCR应表明存在JCPyV原型,从而加快诊断过程。