JC virus VP1 loop-specific polymorphisms are associated with favorable prognosis for progressive multifocal leukoencephalopathy.

JC virus VP1 loop-specific polymorphisms are associated with favorable prognosis for progressive multifocal leukoencephalopathy.
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DOI:
10.1080/13550280802425467
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发表时间:
2009-01
影响因子:
3.2
通讯作者:
Ferrante P
Ferrante P
中科院分区:
医学4区
文献类型:
--
作者:
Delbue S;Branchetti E;Bertolacci S;Tavazzi E;Marchioni E;Maserati R;Minnucci G;Tremolada S;Vago G;Ferrante P

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JC病毒(JCV)是一种人类多瘤病毒,可引起进行性多灶性白质脑病(PML),这是一种主要影响免疫功能低下的致命性脱髓鞘疾病。自从被发现以来,PML一直被认为是一种进展迅速的致命疾病;然而,最近人们初步认为衣壳病毒蛋白中的氨基酸替换与PML临床病程的变化有关。为了更深入地了解PML的发病机制,寻找潜在的预后标记物,从不同临床病程(进展快、慢)的PML患者脑脊液(CSF)和尸检标本中采集了7份脑脊液(CSF)和4份脑组织标本,扩增、克隆和测序了JCVVP1编码区。此外,还收集了9例PML或其他神经系统疾病(OND)患者的尿样,并进行了分析。对编码VP1外环的基因组区域的测序分析显示,在PML进展缓慢的患者中,VP1外环的多态残基仅限于4个位置(74、75、117和128),而从尿液中分离的JCV没有发现明显的突变。总而言之,这些数据表明JCV VP1环突变与PML的良好预后相关。因此,PML进展较慢可能与出现一种毒力较低、复制率较低的JCV株有关。
JC virus (JCV) is a human polyomavirus that causes progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease that mainly affects immunocompromised subjects. Since its discovery, PML has been considered a rapidly progressing fatal disease; however, amino acid substitutions in the capsid viral protein have recently been tentatively associated with changes in PML clinical course. In order to provide more insight to PML pathogenesis and identify potential prognostic markers, seven cerebrospinal fluid (CSF) samples and four brain autopsy samples were collected from patients afflicted with PML with different clinical courses (fast- and slow-progressing), and the JCV VP1 coding region was amplified, cloned and sequenced. In addition, urine samples were collected and analysed from nine patients with PML or other neurological diseases (OND) as a control group. Sequencing analysis of the genomic region encoding the VP1 outer loops revealed polymorphic residues restricted to four positions (74, 75, 117 and 128) in patients with slow PML progression, whereas no significant mutation was found in JCV isolated from urine. Collectively, these data show that JCV VP1 loop mutations are associated with a favourable prognosis for PML. It is therefore possible that slower progression of PML may be related to the emergence of a less virulent JCV strain with a lower replication rate.
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