KSHV strains: the origins and global spread of the virus

KSHV strains: the origins and global spread of the virus
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DOI:
10.1006/scbi.1998.0116
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发表时间:
1999-06-01
影响因子:
14.5
通讯作者:
Hayward, GS
Hayward, GS
中科院分区:
医学1区
文献类型:
--
作者:
Hayward, GS

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来自北美、非洲、中东、亚洲和太平洋地区的650多个KS和PEL肿瘤的KSHV样本的140,000 bp基因组中5个不同位点的核苷酸序列分析显示,它们聚成4个主要亚型(A、B、C和D),这些亚型与患者的地理和种族背景密切相关。特别是,在基因组的极端LHS编码的ORF-K1蛋白亚型显示高达30%的氨基酸变异性,这是由85%的非同义核苷酸取代率引起的。此外,两个替代的高度分歧形式的复杂剪接的ORF-K15基因(P或M)的地图在极端RHS的基因组和基本上不连锁的ORF-K1基因型。我们的结论是:(1)KSKV是一种古老的人类病毒,有几种主要亚型,反映了过去35,000 - 60,000年来现代人类种群的迁移差异;(2)新型免疫球蛋白受体样信号转导蛋白ORF-K1受到异常强烈的生物选择压力;和(3)少数KSHV基因组经历了与相关病毒的重组事件,产生ORF-K15潜伏膜蛋白的两种不同等位基因。
Nucleotide sequence analysis at five distinct loci across the 140,000 bp genomes of more than 650 KSHV samples from KS and PEL tumors from North America, Africa, the Middle East, Asia and the Pacific revealed that they cluster into four major subtypes (A, B, C and D) that have close associations with the geographic and ethnic background of the patients. In particular, the ORF-K1 protein subtypes encoded at the extreme LHS of the genome display up to 30% amino acid variability resulting from 85% non-synonymous nucleotide substitution rates. In addition, two alternative highly diverged forms of the complex spliced ORF-K15 gene (P or M) map at the extreme RHS of the genome and are essentially unlinked to the ORF-K1 genotypes. We conclude that: (1) KSKV is an ancient human virus with several major subtypes that reflect the migrationary divergence of modem human populations over the past 35,000-60,000 years; (2) the novel immunoglobulin receptor-like signal transducing protein ORF-K1 is subject to unusually strong biological selective pressures; and (3) a minority of KSHV genomes have undergone recombination events with a related virus producing two different alles of the ORF-K15 latency membrane protein.