1例宫内感染HIV-1婴儿的病毒准种变化特征研究  

Characteristics of HIV-1 quasispecies evolution in a case of intrauterine HIV infection

作　　者：张园园[1] 魏柯雯[1] 高先[1] 陈巧佩[2] 潘丽璇 王方正 姚均[1] ZHANG Yuanyuan;WEI Kewen;GAO Xian;CHEN Qiaopei;PAN Lixuan;WANG Fangzheng;YAO Jun(National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China;Maternal ＆ Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning 530003;Bengbu Medical College, Bengbu 233000)

机构地区：[1]中国疾病预防控制中心性病艾滋病预防控制中心,北京102206 [2]广西壮族自治区妇幼保健院,南宁530003 [3]蚌埠医学院,安徽蚌埠233000

出　　处：《中国艾滋病性病》2018年第5期444-448,共5页Chinese Journal of Aids & STD

基　　金：国家科技重大专项(2015ZX10001001-002)~~

摘　　要：目的通过比较母婴的Ⅰ型艾滋病病毒（HIV-1）的准种特征,了解病毒垂直传播的规律,并分析三联用药对婴儿体内病毒进化产生的影响。方法收集1例HIV阳性母亲及其所生新生儿各时间点的血液样本,提取全血和血浆中的脱氧核糖核酸（DNA）、核糖核酸（RNA）,经聚合酶链反应（PCR）扩增出HIV-1编码核心蛋白（env）、包膜蛋白（gag）以及多聚酶（pol）的基因片段,进行定性定量、基因亚型和耐药分析;Hiseq高通量测序用来分析各样本准种分布和变化情况。结果新生儿系列样本核酸检测结果均为阳性,母婴两者感染的HIV-1亚型为重组亚型（CRF08_BC）,均未检测到耐药突变株,且产时母婴血浆样本内病毒载量分别为68 700拷贝/mL和102 000拷贝/mL。所有样本经高通量测序后,母亲样本三区内的基因离散率都大于新生儿,但二者样本间的基因离散率均〈1.09%。三区系统进化树显示,新生儿体内的优势准种均来自母亲。新生儿产后样本中：前42天基因离散率稳定,三月龄时离散率开始升高,六月龄时离散率回落;样本内的基因离散率均〈0.85%,与基线样本间的基因离散率均〈0.81%。pol区系统进化树显示相对明显的进化关系。结论母亲与新生儿感染的HIV-1病毒属当地流行亚型,两者有传播关系,新生儿感染了母亲全血样本内的多数优势准种。新生儿三月龄后病毒准种呈现波动性变化,说明抗病毒治疗能影响体内优势准种的分布,但由于样本时间间隔短,系统进化树分析准种进化的能力有限。Objective To compare the characteristics of HIV-1 quasispecies of the mother and infant,so as to know the rules of vertical transmission and analyze the impact of triple therapy on virus evolution in infants.Methods One infant having intrauterine infection of HIV-1 and her mother were selected as our study subject.Blood samples were collected at each time point.DNA and RNA were extracted from the whole blood and plasma respectively.The PCR targeted on three regions（gag,pol and env）of HIV-1 was performed to analyze the subtypes and drug-resistant mutation of the virus.Hiseq high-throughput sequencing was used to analyze the distribution and HIV-1 quasispecies evolution in each specimen.Results The nucleic acid test results of all the infant’s samples were positive and the virus subtype was CRF08_BC.No drug-resistant mutant strains were detected.The viral load of mother and baby were 68 700 cp/ml and 102 000 cp/ml respectively.After high-throughput sequencing of all the samples,the gene dispersal rates of the maternal samples in the three genetic regions were all greater than those of the newborn.However,the genetic divergence between the two samples was less than 1.09%.Phylogenetic trees in the three regions showed that there was a spreading relationship.Among the newborn postnatal samples,the gene dispersal rate was stable in the first 42 days and began to rise at 3 months and dropped at 6 months.The genetic dispersions in the samples were less than0.85% and the genetic dispersions to the baseline samples were less than 0.81%.The phylogenetic tree of the pol region showed a relatively clear evolutionary relationship.Conclusion HIV-1 of the infected mother and newborn is a local subtype.The combination of genetic divergence rate and phylogenetic tree shows a spreading relationship,and the newborn is infected with most dominant quasi-population of the mother.Viral quasispecies show the change of the newborn is fluctuating after three months,indicating that antiviral therapy can affect the distribution of domi

关 键 词：艾滋病病毒 母婴传播 准种 高通量测序 

分 类 号：R373.9[医药卫生—病原生物学]