Human cytomegalovirus glycoprotein N (gpUL73-gN) genomic variants: identification of a novel subgroup, geographical distribution and evidence of positive selective pressure
Human cytomegalovirus glycoprotein N (gpUL73-gN) genomic variants: identification of a novel subgroup, geographical distribution and evidence of positive selective pressure
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DOI：
10.1099/vir.0.18704-0
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发表时间：
2003-03-01
影响因子：
3.8
通讯作者：
Landini, MP
中科院分区：
文献类型：
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作者：
Pignatelli, S;Dal Monte, P;Landini, MP
人巨细胞病毒（HCMV）ORF UL73是一个多态性基因座，编码病毒糖蛋白gpUL73-gN，gC-II包膜复合物的组分。在这项工作中，通过分析从世界各地收集的一大组HCMV临床分离株（223个样品），进一步研究了先前鉴定的gN基因组变体（表示为gN-1、gN-2、gN-3和gN-4）。测序和系统发育分析证实了四种gN基因型的存在，但也允许鉴定属于gN-3基因型的一个新亚组，命名为gN-3b。在gN基因型中估计非同义（d（N））和同义（d（S））核苷酸替换的数目及其比率（d（N）/d（S））以评估正选择的可能性。结果表明，这四个变异体是通过中性（随机）选择进化的，但gN-3和gN-4基因型是通过正选择压力维持的。根据其地理来源对223株HCMV临床分离株进行了细分，并确定了gN流行的四个主要地区：欧洲、中国、澳大利亚和北方美洲。发现gN变体广泛存在，并且在分析的区域内没有任何显著差异，并且没有检测到新的基因型。最后，基于PCR扩增的UL73序列的SacI、Scal和Sa/IA酶切所揭示的RFLP，建立了一种快速、低成本的HCMV临床分离株基因分型方法，以用于临床和流行病学目的。这种技术使我们能够区分所有四种gN基因组变体及其亚型。
Human cytomegalvirus (HCMV) ORF UL73 is a polymorphic locus, encoding the viral glycoprotein gpUL73-gN, a component of the gC-II envelope complex. The previously identified gN genomic variants, denoted gN-1, gN-2, gN-3 and gN-4, were further investigated in this work by analysing a large panel of HCMV clinical isolates collected from all over the world (223 samples). Sequencing and phylogenetic analysis confirmed the existence of the four gN genotypes, but also allowed the identification of a novel subgroup belonging to the gN-3 genotype, which was designated gN-3b. The number of non-synonymous (d(N)) and synonymous (d(S)) nucleotide substitutions and their ratio (d(N)/d(S)) were estimated among the gN genotypes to evaluate the possibility of positive selection. Results showed that the four variants evolved by neutral (random) selection, but that the gN-3 and gN-4 genotypes are maintained by positive selective pressure. The 223 HCMV clinical isolates were subdivided according to their geographical origin, and four main regions of gN prevalence were identified: Europe, China, Australia and Northern America. The gN variants were found to be widespread and represented within the regions analysed without any significant difference, and no new genotype was detected. Finally, for clinical and epidemiological purposes, a rapid and low-cost method for genetic grouping of the HCMV clinical isolates was developed based on the RFLP revealed by Sacl, Scal and Sa/lA digestion of the PCR-amplified UL73 sequence. This technique enabled us to distinguish all four gN genomic variants and also their subtypes.