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儿童和艾滋病患者低传代临床分离株中人巨细胞病毒US28基因的序列分析

Sequence analysis of human cytomegalovirus US28 gene in low-passage clinical isolates from children and AIDS patients.

作者信息

He Rong, Xia Chang, Ruan Qiang, Qi Ying, Ma Yan-Ping, Ji Yao-Hua, Guo Jin-Jin

机构信息

Clinical Genetics Department, The Affiliated Shengjing Hospital, China Medical University, Shenyang, Liaoning of PR China.

出版信息

Acta Biochim Pol. 2011;58(2):231-6. Epub 2011 Jun 16.

Abstract

Human cytomegalovirus (HCMV) is often a dangerous opportunistic pathogen that causes significant morbidity and mortality in newborn children and immunocompromised patients. The different symptoms and tissue tropisms of HCMV infection may result from genetic polymorphism. This study investigated the sequence variability of the HCMV US28 ORF, which shows sequence homology to the G protein-coupled receptor. HCMV isolated from suspected pediatric cases and isolates from AIDS patients were compared in order to examine the possible associations between polymorphisms and pathogenesis. Seventy children with suspected congenital HCMV infection, who suffered from jaundice (47), megacolon (10), and microcephaly (13), and 17 AIDS patients, were studied. Mutation was prevalent among the sequences of US28, with a focus on the two ends of US28. The important functional groups of US28 are highly conserved. An unrooted tree showed that all sequences from suspected congenitally infected infants and AIDS patients were divided into three groups. Comparison showed that most of the sequences (12/17) from pediatric patients were included in the first group (G1), whereas most of the sequences (11/17) from AIDS patients were included in the third group (G3). The specific high mutation sites in US28 from children were located at the C terminus of the protein, whereas those from AIDS patients were located at the N terminus. We demonstrated the existence of polymorphisms among the US28 genes of clinical isolates of HCMV from infants with suspected congenital infection. Comparison of US28 sequences from AIDS patients with those from children showed that both sequences have their own specific high mutation points.

摘要

人巨细胞病毒(HCMV)通常是一种危险的机会性病原体,可导致新生儿和免疫功能低下患者出现严重的发病和死亡情况。HCMV感染的不同症状和组织嗜性可能源于基因多态性。本研究调查了HCMV US28开放阅读框的序列变异性,该开放阅读框与G蛋白偶联受体具有序列同源性。对从疑似儿科病例中分离出的HCMV以及从艾滋病患者中分离出的毒株进行比较,以检查多态性与发病机制之间的可能关联。研究了70例疑似先天性HCMV感染的儿童,他们患有黄疸(47例)、巨结肠(10例)和小头畸形(13例),以及17例艾滋病患者。突变在US28序列中普遍存在,集中在US28的两端。US28的重要功能基团高度保守。一棵无根树显示,来自疑似先天性感染婴儿和艾滋病患者的所有序列被分为三组。比较表明,儿科患者的大多数序列(12/17)包含在第一组(G1)中,而艾滋病患者的大多数序列(11/17)包含在第三组(G3)中。儿童US28中特定的高突变位点位于蛋白质的C末端,而艾滋病患者的高突变位点位于N末端。我们证明了疑似先天性感染婴儿的HCMV临床分离株的US28基因中存在多态性。艾滋病患者与儿童的US28序列比较表明,两者序列都有各自特定的高突变点。

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