Agostini H T, Ryschkewitsch C F, Brubaker G R, Shao J, Stoner G I
Laboratory of Experimental Neuropathology, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland, USA.
Arch Virol. 1997;142(4):637-55. doi: 10.1007/s007050050108.
The central demyelinating disease progressive multifocal leukoencephalopathy (PML) is caused by the human polyomavirus JC virus (JCV). JCV evolved as geographically based genotypes of which Type 3 is an African variant first characterized in HIV-1 positive patients from Tanzania. This study reports the complete sequence of five JCV Type 3 strains. The entire JCV genome was PCR amplified from urine specimens of three African and two African-American individuals. The African consensus sequence was compared to the Type 1 and Type 2 prototype strains, JCV (Mad-1) and JCV(GS/B), respectively. Type 3 differed in 2.2% of its coding region genome from JCV (Mad-1) and in 1.3% from JCV(GS/B). Within the coding region the sequence variation among the three types was higher in the capsid protein VP1 and in the regulatory protein large T antigen than in the agnoprotein or in VP2/3. Notable Type 3-specific changes were located at sites adjacent to the zinc finger motif and near the major donor and acceptor splice junctions of large T antigen. Four of the five urinary Type 3 strains had an unrearranged, archetypal regulatory region. African strain #309 showed a 10-bp deletion at a location similar to that previously described for #307 from Tanzania. The African-American Type 3 strain #312 was closely related to the African consensus sequence. The complete genome of a urinary JCV strain from another African-American male, previously reported as a possible Type 5, showed a sequence difference of only 0.52% from the Tanzanian consensus and has been reclassified as a subtype of Type 3.
中枢脱髓鞘疾病进行性多灶性白质脑病(PML)由人多瘤病毒JC病毒(JCV)引起。JCV进化为基于地理区域的基因型,其中3型是一种非洲变体,最初在来自坦桑尼亚的HIV-1阳性患者中得以鉴定。本研究报告了5株JCV 3型毒株的完整序列。从3名非洲人和2名非裔美国人的尿液标本中通过PCR扩增出完整的JCV基因组。将非洲人共有的序列分别与1型和2型原型毒株JCV(Mad-1)和JCV(GS/B)进行比较。3型在其编码区基因组中与JCV(Mad-1)的差异为2.2%,与JCV(GS/B)的差异为1.3%。在编码区内,三种类型之间的序列变异在衣壳蛋白VP1和调节蛋白大T抗原中比在小衣壳蛋白或VP2/3中更高。3型特异性的显著变化位于锌指基序附近以及大T抗原的主要供体和受体剪接连接点附近。5株尿液3型毒株中有4株具有未重排的原型调节区。非洲毒株#309在一个位置出现了10个碱基对的缺失,该位置与先前描述的来自坦桑尼亚的#307相似。非裔美国人3型毒株#312与非洲人共有序列密切相关。另一名非裔美国男性尿液中一株JCV毒株的完整基因组,先前报告可能为5型,其与坦桑尼亚人共有序列的差异仅为0.52%,现已重新分类为3型的一个亚型。