Jensen P N, Major E O
Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Neurovirol. 2001 Aug;7(4):280-7. doi: 10.1080/13550280152537102.
The human polyomavirus JCV is responsible for the central nervous system (CNS) demyelination observed in cases of progressive multifocal leukoencephalopathy (PML). Lytic infection of oligodendrocytes, the cells that constitute the basis of myelin in the CNS, is established by JCV in conjunction with immunosuppressive conditions. Beyond this, however, many questions related to JCV pathogenesis remain unanswered. The JCV regulatory region is a hypervariable noncoding sequence positioned between the early and late protein-coding regions. The particular nucleotide sequence of a JCV regulatory region affects levels of viral transcription and replication. Modifications to this promoter/enhancer structure can alter the cellular host range and may be responsible for switching JCV between states of lytic and latent infection. The regulatory region structure has, therefore, been used to distinguish JCV variants. Nucleotide sequencing studies have uncovered numerous variations of regulatory region structure. Until now, however, no inclusive nomenclature existed that linked variants by regulatory region structure and/or activity. We have arranged all known variant JCV regulatory regions into quadrants according to the integration of particular sequence sections and repetition of sequence section groups. This arrangement of regulatory regions results in an updated nomenclature that is well-suited for describing the relationships between JCV variants. Four distinct structural forms (I-S, I-R, II-S, and II-R) are defined along with tissue tropisms. This design provides logical connections between the variant regulatory regions and may be useful for elucidating crucial steps in JCV pathogenesis.
人类多瘤病毒JCV是进行性多灶性白质脑病（PML）病例中观察到的中枢神经系统（CNS）脱髓鞘的病因。在免疫抑制条件下，JCV会在少突胶质细胞（构成中枢神经系统髓磷脂基础的细胞）中建立裂解感染。然而除此之外，许多与JCV发病机制相关的问题仍未得到解答。JCV调控区是位于早期和晚期蛋白质编码区之间的高变非编码序列。JCV调控区的特定核苷酸序列会影响病毒转录和复制水平。对该启动子/增强子结构的修饰可改变细胞宿主范围，并可能导致JCV在裂解感染和潜伏感染状态之间转换。因此，调控区结构已被用于区分JCV变体。核苷酸测序研究发现了调控区结构的众多变体。然而，到目前为止，还没有一个包容性的命名法能够通过调控区结构和/或活性将变体联系起来。我们根据特定序列片段的整合和序列片段组的重复，将所有已知的JCV调控区变体排列到象限中。这种调控区排列产生了一种更新的命名法，非常适合描述JCV变体之间的关系。定义了四种不同的结构形式（I-S、I-R、II-S和II-R）以及组织嗜性。这种设计提供了变体调控区之间的逻辑联系，可能有助于阐明JCV发病机制中的关键步骤。
