未经证实::JC多瘤病毒是进行性多灶性白质脑病(PML)的病原体,一种由少突胶质细胞溶解感染引起的脱髓鞘疾病,可能在免疫抑制个体中发展:HIV-1感染或接受免疫抑制治疗的个体。了解JCPyV的生物学对于适当的患者管理是必要的,诊断测试的发展,和风险分层。
UNASSIGNED::该综述涵盖了不同的专业领域,包括在不同的身体隔室中检测到的JCPyV菌株的基因组表征(尿液,PML患者的血浆和脑脊液),病毒突变,分子诊断,病毒miRNA和疾病。
UNASSIGNED::分子生物学技术的实施提高了我们对JCPyV生物学的理解。病毒基因组的深度测序分析显示,PML患者的脑脊液中存在病毒准种,其特征是非编码控制区重排和VP1突变。这些嗜神经JCPyV变体呈现增强的复制和改变的细胞嗜性,这有助于PML发展。监测这些变异可能与鉴定处于PML风险的患者有关。靶向LTAG和原型NCCR的多重实时PCR可用于鉴定它们。未能放大NCCR应表明存在加速诊断过程的JCPyV原型。
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 LTAg 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.