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宫内病毒传播后母婴的基因组1型人类免疫缺陷病毒RNA变异

Genomic human immunodeficiency virus type 1 RNA variation in mother and child following intra-uterine virus transmission.

作者信息

Mulder-Kampinga G A, Kuiken C, Dekker J, Scherpbier H J, Boer K, Goudsmit J

机构信息

Department of Virology, Academic Medical Center, Amsterdam, The Netherlands.

出版信息

J Gen Virol. 1993 Sep;74 ( Pt 9):1747-56. doi: 10.1099/0022-1317-74-9-1747.

DOI:10.1099/0022-1317-74-9-1747
PMID:8376956
Abstract

In order to study the relationship between virus populations in a human immunodeficiency virus type 1 (HIV-1)-infected mother and her infant, we analysed a 276 bp fragment, including the V3 region, of genomic HIV-1 RNA purified from serum. Samples were collected from the mother 6, 4 and 2 months prior to delivery, during delivery and 10 months after childbirth (samples MA to ME, respectively) and from the infant at birth (cord blood) and the ages of 6 weeks and 9 months. A heterogeneous sequence population was observed in the maternal samples (mean nucleotide variation of 2.4 to 4.2%, range 0 to 8.3%). Until the age of 6 weeks the sequence population in the infant was highly homogeneous (mean nucleotide variation < or = 0.7%, range 0 to 2.5%). At 9 months of age, the infant's virus population showed more heterogeneity (mean nucleotide variation of 1.8%, range 0.4 to 3.6%) and a drift in the consensus sequence was observed. The evolution of the V3 region in the mother was characterized by accumulation of amino acid substitutions diverging from the virus population observed in the infant. The mean nucleotide distance between the maternal sequence populations and the sequence population of the child at birth was 2.8, 2.6, 3.7, 5.2 and 5.3% for the samples MA, MB, MC, MD and ME, respectively. Nearly complete replacement at position 308, previously described as antigenically important, from a proline to a histidine was observed during pregnancy, whereas all clones of the child's virus at birth and at 6 weeks contained a proline at that position. In conclusion, intra-uterine transmission is associated with a homogeneous sequence population in the child at birth, which is more closely related to the sequence population present in the mother during the first and second trimester of pregnancy than to the sequence population at delivery.

摘要

为研究人类免疫缺陷病毒1型(HIV-1)感染母亲及其婴儿体内病毒群体之间的关系,我们分析了从血清中纯化的HIV-1基因组RNA的一个276 bp片段,该片段包括V3区。在分娩前6个月、4个月和2个月、分娩期间以及产后10个月(分别为样本MA至ME)采集母亲的样本,并在婴儿出生时(脐带血)以及6周龄和9月龄时采集婴儿样本。在母亲样本中观察到异质序列群体(平均核苷酸变异为2.4%至4.2%,范围为0至8.3%)。直到6周龄,婴儿体内的序列群体高度同质(平均核苷酸变异≤0.7%,范围为0至2.5%)。在9月龄时,婴儿的病毒群体表现出更多的异质性(平均核苷酸变异为1.8%,范围为0.4至3.6%),并且观察到共有序列发生了漂移。母亲体内V3区的进化特征是氨基酸取代的积累,这些取代与婴儿体内观察到的病毒群体不同。母亲序列群体与出生时儿童序列群体之间的平均核苷酸距离,样本MA、MB、MC、MD和ME分别为2.8%、2.6%、3.7%、5.2%和5.3%。在怀孕期间,观察到先前被描述为具有抗原重要性的308位几乎完全发生了从脯氨酸到组氨酸的替换,而出生时和6周龄时儿童病毒的所有克隆在该位置都含有脯氨酸。总之,宫内传播与出生时儿童体内的同质序列群体相关,该群体与妊娠头三个月和第二个月母亲体内存在的序列群体的关系比与分娩时的序列群体更密切。

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