Dong Niuniu, Cao Lingfeng, Zheng Danni, Su Liyun, Lu Lijuan, Dong Zuoquan, Xu Menghua, Xu Jin
Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.
Front Pediatr. 2023 Mar 15;11:1112645. doi: 10.3389/fped.2023.1112645. eCollection 2023.
Cytomegalovirus (CMV) is the leading cause of congenital infections worldwide and contributes to long-term sequelae in neonates and children. CMV envelope glycoproteins play a vital role in virus entry and cell fusion. The association between CMV polymorphisms and clinical outcomes remains controversial. The present study aims to demonstrate the distribution of glycoprotein B (gB), H (gH) and N (gN) genotypes in congenitally CMV (cCMV) infected symptomatic infants and attempts to figure out the association between viral glycoprotein genotypes and clinical outcomes.
Genotyping of gB, gH and gN was performed in 42 cCMV symptomatic infants and 149 infants with postnatal CMV (pCMV) infection in Children's hospital of Fudan university. Nested PCR, gene sequencing and phylogenetic analyses were used to identify the genotypes.
Our study demonstrated that: 1. The CMV gB1, gH1 and gN1 were the predominant genotypes among symptomatic cCMV infected infants, while gB1, gH1 and gN3a were more prevalent in pCMV group. gH1 genotype has a significant association with symptomatic cCMV infection (= 0.006). 2. No significant correlation was found between CMV genotypes and hearing impairment. However, gH1 was more prevalent among cCMV infected infants with moderate/severe hearing loss although without statistical difference (= 0.130). 3. gB3 was more prevalent among infants with skin petechiae (= 0.049) and found to be associated with an increased risk of skin petechiae (OR = 6.563). The gN4a subtype was significantly associated with chorioretinitis due to cCMV infection (= 0.007). 4. Urine viral loads were not significantly associated with different genotypes or hearing impairment among symptomatic cCMV infected infants.
Our findings demonstrated the overall distribution of gB, gH and gN genotypes in infants with symptomatic cCMV infection in Shanghai for the first time. The findings in our study may suggest a possible association between gH1 genotype and early infancy hearing loss. gB3 genotype was associated with a 6.5-fold increased risk of petechiae while gN4a strongly correlated with chorioretinitis due to cCMV infection. No significant correlation was found between urine viral loads and CMV genotypes or hearing impairment in cCMV infected infants.
巨细胞病毒（CMV）是全球先天性感染的主要原因，可导致新生儿和儿童出现长期后遗症。CMV包膜糖蛋白在病毒进入和细胞融合过程中起着至关重要的作用。CMV基因多态性与临床结局之间的关联仍存在争议。本研究旨在阐明先天性CMV（cCMV）感染的有症状婴儿中糖蛋白B（gB）、H（gH）和N（gN）基因型的分布情况，并试图找出病毒糖蛋白基因型与临床结局之间的关联。
在复旦大学附属儿科医院对42例cCMV感染有症状的婴儿和149例出生后感染CMV（pCMV）的婴儿进行gB、gH和gN基因分型。采用巢式PCR、基因测序和系统发育分析来鉴定基因型。
我们的研究表明：1. 在有症状的cCMV感染婴儿中，CMV gB1、gH1和gN1是主要基因型，而在pCMV组中gB1、gH1和gN3a更为常见。gH1基因型与有症状的cCMV感染显著相关（P = 0.006）。2. 未发现CMV基因型与听力障碍之间存在显著相关性。然而，gH1在中度/重度听力损失的cCMV感染婴儿中更为常见，尽管无统计学差异（P = 0.130）。3. gB3在有皮肤瘀点的婴儿中更为常见（P = 0.049），且发现与皮肤瘀点风险增加相关（OR = 6.563）。gN4a亚型与cCMV感染所致脉络膜视网膜炎显著相关（P = 0.007）。4. 在有症状的cCMV感染婴儿中，尿病毒载量与不同基因型或听力障碍无显著相关性。
我们的研究首次阐明了上海有症状的cCMV感染婴儿中gB、gH和gN基因型的总体分布情况。我们的研究结果可能提示gH1基因型与婴儿早期听力损失之间可能存在关联。gB3基因型与瘀点风险增加6.5倍相关，而gN4a与cCMV感染所致脉络膜视网膜炎密切相关。在cCMV感染婴儿中，未发现尿病毒载量与CMV基因型或听力障碍之间存在显著相关性。
