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与母婴传播相关的人类免疫缺陷病毒1型p17基质蛋白基序的特征分析

Characterization of human immunodeficiency virus type 1 p17 matrix protein motifs associated with mother-to-child transmission.

作者信息

Narwa R, Roques P, Courpotin C, Parnet-Mathieu F, Boussin F, Roane A, Marce D, Lasfargues G, Dormont D

机构信息

Service de Neurovirologie, Département de Recherche Medicale, Direction des Sciences du Vivant, Service de Santé des Armées, Commissariat a l'Energie Atomique, France.

出版信息

J Virol. 1996 Jul;70(7):4474-83. doi: 10.1128/JVI.70.7.4474-4483.1996.

Abstract

In order to determine if viral selection occurs during mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1), we used a direct solid-phase sequencing method to sequence the p17 matrix protein-encoding regions of viral isolates from 12 HIV-1-infected mother-and-child pairs, 4 infected infants, 4 transmitting mothers, and 22 nontransmitting mothers and compared the sequences. The blood samples were collected during the delivery period for the mothers and during the first month of life for most of the children. The p17 nucleic sequences were distributed among several clades corresponding to the HIV-1 A, B, and G subtypes. At the amino acid level, no significant differences within the known p17 functional regions were observed among the subtypes. Statistical analyses could be performed with the B subtype. Within the major p17 antibody binding site, a constant KIEEEQN motif (amino acids 103 to 109) was found in all mother-and-child isolates from the B subtype. On the other hand, 9 of 17 nontransmitting mother isolates were variable in this 103 to 109 region. Thus, this motif was significantly associated with the transmitting status (chi square, P = 0.0034). A valine residue at position 104 was significantly associated with the nontransmitting phenotype (chi square, P = 0.014), suggesting that it has a protective role during vertical transmission. The C-terminal end of p17 was globally conserved among nontransmitting mother isolates (chi square, P = 0.0037). These results might improve the understanding of the pathogenesis of HIV-1 vertical transmission and might allow the screening of seropositive mothers by a rapid molecular or peptide test.

摘要

为了确定在人类免疫缺陷病毒1型(HIV-1)母婴传播过程中是否发生病毒选择,我们使用直接固相测序方法对来自12对HIV-1感染母婴、4名感染婴儿、4名传播病毒的母亲以及22名未传播病毒的母亲的病毒分离株中编码p17基质蛋白的区域进行测序,并比较序列。母亲的血样在分娩期采集,大多数儿童的血样在出生后第一个月采集。p17核酸序列分布在对应于HIV-1 A、B和G亚型的几个进化枝中。在氨基酸水平上,各亚型在已知的p17功能区域内未观察到显著差异。可以对B亚型进行统计分析。在主要的p17抗体结合位点,在所有B亚型的母婴分离株中发现了一个恒定的KIEEEQN基序(氨基酸103至109)。另一方面,17株未传播病毒的母亲分离株中有9株在这个103至109区域是可变的。因此,这个基序与传播状态显著相关(卡方检验,P = 0.0034)。第104位的缬氨酸残基与未传播表型显著相关(卡方检验,P = 0.014),表明它在垂直传播过程中具有保护作用。p17的C末端在未传播病毒的母亲分离株中总体上是保守的(卡方检验,P = 0.0037)。这些结果可能会增进对HIV-1垂直传播发病机制的理解,并可能允许通过快速分子或肽检测对血清反应阳性的母亲进行筛查。

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