Human cytomegalovirus UL144 open reading frame: Sequence hypervariability in low-passage clinical isolates
Human cytomegalovirus UL144 open reading frame: Sequence hypervariability in low-passage clinical isolates
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DOI：
10.1128/jvi.73.12.10040-10050.1999
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发表时间：
1999-12-01
影响因子：
5.4
通讯作者：
Bremer, JW
中科院分区：
文献类型：
--
作者：
Lurain, NS;Kapell, KS;Bremer, JW
人巨细胞病毒（HCMV）在体内感染许多器官和细胞类型，导致HCMV疾病和组织嗜性可能与特定序列变异有关的假设。HCMV变异株的一个潜在组分是UL 144开放阅读框（ORF），其编码疱疹病毒进入介体HveA的同源物，HveA是肿瘤坏死因子受体超家族的成员。45株低传代临床分离株的UL 144 ORF序列分析显示出显著的菌株特异性变异。在单个分离株中，531个位置中多达21%发生核苷酸替换，导致预测的176个氨基酸序列中大约相同百分比的替换。系统发育分析表明，核苷酸和氨基酸序列分为三个主要群体。为了进行基因型比较，还对包含糖蛋白B（gB）基因蛋白水解切割位点的已知高变区进行了测序。所有的分离株都可以根据四个已知的gB组进行分型;然而，gB和UL 144序列组似乎在遗传学上不连锁。预测的UL 144产物与肿瘤坏死因子受体家族成员的同源性，沿着UL 144 ORF的出乎意料的高水平的序列变异性，表明预测的产物可能在HCMV感染性和随后的宿主疾病中起作用。
Human cytomegalovirus (HCMV) infects a number of organs and cell types in vivo, leading to the hypothesis that HCMV disease and tissue tropism may be related to specific sequence variants. A potential component of HCMV variant strains is the UL144 open reading frame (ORF), which encodes a homologue of the herpesvirus entry mediator, HveA, a member of the tumor necrosis factor receptor superfamily. Sequence analysis of the UL144 ORF in 45 low-passage clinical isolates demonstrated significant strain-specific variability. In individual isolates, nucleotide substitutions occur at up to 21% of the 531 positions, resulting in approximately the same percentage of substitutions in the predicted 176-amino-acid sequence. Phylogenetic analysis indicated that the nucleotide and amino acid sequences diverge into three major groups. For genotypic comparison, the known hypervariable region encompassing the proteolytic cleavage site of the glycoprotein B (gB) gene was also sequenced. All of the isolates could be typed according to the four known gB groups; hoc-ever, the gB and UL144 sequence groups appeared to be phylogenetically unlinked. The predicted UL144 product homology with tumor necrosis factor receptor family members, along with the unexpectedly high level of sequence variability of the UL144 ORF, suggests that the predicted product may play a role in HCMV infectivity and subsequent host disease.