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目的探讨编码包膜糖蛋白的UL73基因多态性与先天性人巨细胞病毒(HCMV)症状性感染的相关性。方法采集2010年11月至2012年2月及2013年1月至2014年6月在本院出生的新生儿尿液进行HCMV感染筛查,选择确诊为先天性HCMV感染的患儿,于1、3、6、12个月进行体检及临床检查,包括头颅超声、脑干听性诱发电位筛查、肝功能、血常规检查等。根据1年内有无临床症状将患儿分为无症状组和有症状组。对其尿液样本进行HCMV-DNA提取、UL73基因测序及gN分型。结果共68例确诊为HCMV感染的新生儿随诊到12个月,其中无症状41例,有症状27例。对68份尿液样本进行UL73全序列PCR扩增,获得57株阳性株,序列测定gN1、gN2、gN3、gN4型分别为9、5、11、32例。gN1、gN2、gN3、gN4各型症状性感染发生率分别为22.2%、40.0%、18.2%和62.5%,差异有统计学意义(P=0.028),gN4型高于gN1和gN3型(P<0.05)。结论 gN1和gN3型可能代表不致病或最温和毒性的gN蛋白类型,gN2及gN4型有症状比例及严重程度高,gN4型是最主要且严重的毒性类型,建议对gN2及gN4型患儿加强管理和随访。
Objective To investigate the association between UL73 gene polymorphism of envelope glycoprotein and symptomatic infection of congenital human cytomegalovirus (HCMV). Methods The neonatal urine samples from November 2010 to February 2012 and January to June 2014 in our hospital were screened for HCMV infection and selected children diagnosed as congenital HCMV infection. 3,6,12 months for physical examination and clinical examination, including head ultrasound, brainstem auditory evoked potentials screening, liver function, blood tests and so on. Children were divided into asymptomatic group and symptomatic group according to the presence or absence of clinical symptoms in one year. Urine samples were subjected to HCMV-DNA extraction, UL73 gene sequencing and gN typing. Results A total of 68 newborns diagnosed with HCMV infection were followed up for 12 months, of which 41 were asymptomatic and 27 were symptomatic. Sixty-eight urine samples were amplified by UL73, and 57 positive strains were obtained. Sequences of gN1, gN2, gN3 and gN4 were 9, 5, 11 and 32 respectively. The incidences of gN1, gN2, gN3 and gN4 were 22.2%, 40.0%, 18.2% and 62.5%, respectively, with statistical significance (P = 0.028) and gN4 higher than those of gN1 and gN3 (P < 0.05). Conclusion gN1 and gN3 may represent non-pathogenic or the most mild toxic gN protein type, gN2 and gN4 type symptoms and high severity, gN4 type is the most important and serious types of toxicity, it is recommended for gN2 and gN4 children Strengthen management and follow-up.