Complete genome of a JC virus genotype type 6 from the brain of an African American with progressive multifocal leukoencephalopathy.

Journal of human virology Pub Date : 1998-05-01
H T Agostini, C F Ryschkewitsch, G L Stoner
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Abstract

Objectives: The major genotypes of the human polyomavirus JC (JCV) include type 1 (European), type 2 (Asian), type 3 (African), and type 4 (United States). Here we report characterization of the complete genome of a genotype obtained from the brain of an African American with systemic lupus erythematosus (SLE) and progressive multifocal leukoencephalopathy (PML).

Study design/methods: DNA extracted from JCV-infected brain tissue was subjected to whole-genome polymerase chain reaction (PCR) amplification and direct cycle sequencing. Relations to other JCV genotypes and the predicted amino acid sequence were analyzed.

Results: This African-American type 6 strain (#601) differs from strains of all other genotypes in about 2% of its DNA sequence. The length of the total coding region of strain #601 is increased to 4855 bp by the insertion of a single nucleotide in the large T-antigen intron. This strain, originally placed with the type 2 group on the basis of its sequence in the VT-intergenic region, is very closely related to strains recently identified in the urine of individuals from Ghana, West Africa.

Conclusions: This is the first example of an African JCV genotype identified in the brain of an African-American PML patient. The extent of sequence divergence of JCV type 6 suggests a split of type 6 strains before the separation of types 2 and 3. These findings confirm that distinctive African genotypes of JCV have been maintained in the African-American population and that they are capable of causing PML.

非裔美国人进行性多灶性白质脑病脑组织中6型JC病毒的全基因组分析
目的:人多瘤病毒JC (JCV)的主要基因型包括1型(欧洲)、2型(亚洲)、3型(非洲)和4型(美国)。在这里,我们报告了从患有系统性红斑狼疮(SLE)和进行性多灶性白质脑病(PML)的非洲裔美国人的大脑中获得的基因型的全基因组特征。研究设计/方法:从jcv感染的脑组织中提取DNA,进行全基因组聚合酶链反应(PCR)扩增和直接循环测序。分析了其与其他JCV基因型的关系及预测的氨基酸序列。结果:这种非裔美国人6型菌株(#601)与所有其他基因型的菌株在大约2%的DNA序列上不同。通过在大t抗原内含子中插入单个核苷酸,菌株#601的总编码区长度增加到4855 bp。该菌株最初根据其在vt -基因间区的序列被归入2型组,与最近在西非加纳个体尿液中发现的菌株非常密切相关。结论:这是在非裔美国PML患者的大脑中发现的第一例非洲JCV基因型。6型JCV的序列分化程度表明,在2型和3型分离之前,有6型菌株的分裂。这些发现证实,独特的非洲基因型JCV在非洲裔美国人群体中一直存在,并且它们能够引起PML。
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