Genotypic analysis at multiple loci across Kaposi's sarcoma herpesvirus (KSHV) DNA molecules: clustering patterns, novel variants and chimerism
Genotypic analysis at multiple loci across Kaposi's sarcoma herpesvirus (KSHV) DNA molecules: clustering patterns, novel variants and chimerism
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DOI：
10.1016/s1386-6532(01)00205-0
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发表时间：
2002-01-01
影响因子：
8.8
通讯作者：
Hayward, GS
中科院分区：
文献类型：
--
作者：
Zong, JC;Ciufo, DM;Hayward, GS
背景资料：人卡波西肉瘤相关疱疹病毒（KSHV）的基因组显示出几种水平的DNA序列异质性和亚群，其在相关人群中显示出独特的聚类模式。高变ORF-K1蛋白的四种主要亚型模式与现代人从东非迁移出来的主要散居地密切相关，表明KSHV是一种古老的人类病毒，主要以家族方式传播，因此重组率非常低。然而，嵌合基因组也已被检测到，特别是关于ORF-K15基因的P对M等位基因的存在。目的：进一步了解KSHV的遗传组织和进化史，特别是关于可能的新亚型、重组基因组、恒定区基因座和特定种族群体或同一地理区域经典与流行病例之间的聚类。Stitch，设计：对从以色列、韩国、西西里、斯堪的纳维亚、巴西、乌干达、南非和美国的70名新KSHV阳性患者收集的诊断样品的最左侧和右侧的ORF-K1和ORF-K15基因以及6个其它内部基因座进行直接PCR DNA测序。结果与结论：我们来自许多不同人群的超过135个KSHV基因组的总体结果现在为KSHV基因组的七种不同亚型（称为A/P、B/P、C/P、D/P、M、N和Q）提供了证据。然而，两种最密切相关的亚型（A/P和C/P）仅在基因组的LHS侧分化，而三种最远相关的形式（M，N和Q）似乎仅作为小的嵌合片段存在，这些片段是更古老的病毒形式的RHS的残留物。通过分析在撒哈拉以南非洲占主导地位的B亚型基因组中的多个保守位点，我们现在还可以识别出三到四个不同的B基因组亚组，它们具有不同的细胞间和细胞内嵌合模式。来自以色列的经典KSHV基因组分析显示，被称为Al'的ORF-K1分支在来自俄罗斯的德系犹太移民中占主导地位，而C2和C6变体在北非塞法迪犹太人中占主导地位。包含C2或C3 ORF-K基因的各种嵌合基因组在欧洲和亚洲的经典KS病例中传播，包括以色列、西西里、斯堪的纳维亚、韩国和台湾。美国经典型KSHV与艾滋病相关型KSHV的基因组比较表明，KSHV最初是由来自北方和东欧、地中海和撒哈拉以南非洲流行地区的移民后代携带的内源性病毒的一个子集重新激活和传播而产生的。(C)2002 Elsevier Science B. V.保留所有权利。
Background: the genomes of human Kaposi's sarcoma-associated herpesvirus (KSHV) display several levels of DNA sequence heterogeneity and subgrouping that show distinctive clustering patterns in related human populations. The four major subtype patterns for the hypervariable ORF-K1 protein correlate closely with the principal diasporas resulting from the migration of modern humans out of East Africa and suggest that KSHV is an ancient human virus that is transmitted primarily in a familial fashion with consequent very low recombination rates. However, chimeric genomes have also been detected, especially with regard to the presence of P versus M alleles of the ORF-K15 gene. Objectives: to understand further the genetic organization and evolutionary history of KSHV, especially with regard to possible new subtypes, recombinant genomes, constant region loci and clustering in particular ethnic groups or among classic versus epidemic cases in the same geographic area. Stitch, design: direct PCR DNA sequencing was carried out on the ORF-K1 and ORF-K15 genes at the extreme left and right hand sides, as well as on six other internal loci of diagnostic samples collected from 70 new KSHV-positive patients in Israel, South Korea, Sicily, Scandinavia, Brazil, Uganda, South Africa and the US. Results and conclusions: our overall results from more than 135 KSHV genomes from many different human population groups now provides evidence for seven distinct subtypes of KSHV genomes (referred to as A/P, B/P, C/P, D/P, M, N and Q). However, the two most closely related subtypes (A/P and C/P) are only differentiated at the LHS side of the genome, and the three most distantly related forms (M, N and Q) appear to exist only as small chimeric segments that are remnants from the RHS of more ancient forms of the virus. By analyzing multiple conserved loci across the B subtype genomes that predominate in sub-Saharan Africa, we can also now recognize three to four distinct B genome subgroups with varying patterns of inter and intratypic mosaicism. Analysis of classic KSHV genomes from Israel has revealed that the ORF-K1 clade referred to as Al' predominates in Ashkenazi Jewish immigrants from Russia, whereas C2 and C6 variants predominate in North African Sephardi Jews. A variety of chimeric genomes containing C2 or C3 ORF-K genes are disseminated among classic KS cases throughout Europe and Asia including Israel, Sicily, Scandinavia, South Korea, and Taiwan. Comparison of the genomes from classic versus AIDS-associated KSHV in the US indicates that it was derived originally by reactivation and spread of a subset of the endogenous viruses carried by descendants of immigrants from endemic areas of Northern and Eastern Europe, the Mediterranean and sub-Saharan Africa. (C) 2002 Elsevier Science B.V. All rights reserved.