Characterization of the VP1 loop mutations widespread among JC polyomavirus isolates associated with progressive multifocal leukoencephalopathy

Characterization of the VP1 loop mutations widespread among JC polyomavirus isolates associated with progressive multifocal leukoencephalopathy
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DOI:
10.1016/j.bbrc.2005.06.012
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发表时间:
2005-08-05
影响因子:
3.1
通讯作者:
Yogo, Y
Yogo, Y
中科院分区:
生物学4区
文献类型:
--
作者:
Zheng, HY;Ikegaya, H;Yogo, Y

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最近,我们发现JC多瘤病毒(JCPyV)与进行性多灶性白质脑病(PML)频繁发生氨基酸取代(指定VP1环突变)的主要衣壳蛋白,VP1的外环。为了进一步表征突变,我们分析了20例PML患者脑组织或脑脊液样本中JCPyV基因组的VP1区域。VP1环突变的发生频率远远高于沉默突变。多态性残基基本上限于BC环内的三个位置(55、60和66)、DE环内的一个位置(123)和HI环内的三个位置(265、267和269)。大多数多态性残基的突变显示出向特定氨基酸变化的趋势。最后,我们提出了证据表明,VP1环突变与PML的进展。这些发现应该形成阐明VP1环突变的生物学意义的基础。(c)2005年爱思唯尔公司All rights reserved.
Recently, we found that JC polyomavirus (JCPyV) associated with progressive multifocal leukoencephalopathy (PML) frequently undergoes amino acid substitutions (designated VP1 loop mutations) in the outer loops of the major capsid protein, VP1. To further characterize the mutations, we analyzed the VP1 region of the JCPyV genome in brain-tissue or cerebrospinal fluid samples from 20 PML patients. VP1 loop mutations occurred far more frequently than silent mutations. Polymorphic residues were essentially restricted to three positions (55, 60, and 66) within the BC loop, one (123) within the DE loop, and three (265, 267, and 269) within the HI loop. The mutations at most polymorphic residues showed a trend toward a change to specific amino acids. Finally, we presented evidence that the VP1 loop mutations were associated with the progression of PML. These findings should form the basis for elucidating the biological significance of the VP1 loop mutations. (c) 2005 Elsevier Inc. All rights reserved.