Virologic risk factors for vertical transmission of HIV type 1 in Puerto Rico
Virologic risk factors for vertical transmission of HIV type 1 in Puerto Rico
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DOI：
10.1089/088922202753614218
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发表时间：
2002-04-10
影响因子：
1.5
通讯作者：
Meléndez-Guerrero, LM
中科院分区：
文献类型：
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作者：
Arroyo, MA;Tien, H;Meléndez-Guerrero, LM
由于实施了抗病毒治疗，波多黎各的HIV-1垂直传播显著减少。几项研究表明，最初从感染婴儿中回收的HIV-1分离株的表型通常是快速复制、感染巨噬细胞并优先使用CCR 5辅助受体的表型。我们的假设是，HIV-1非传播者和传播者母亲之间存在病毒基因型和表型差异。从波多黎各围产期人群中分析病毒DNA样本和病毒分离株。对DNA样品进行异源双链追踪测定（HTA）以检测每个样品内的env V3进化变体和异质性程度。从每个患者中克隆HIV-1 C2-V3变体，以研究各组之间的序列变异。用重复测量线性回归分析法分析病毒分离株在巨噬细胞和GHOST CCR 5细胞中复制动力学的差异。HTA分析显示，只有两个非递质患者样本显示存在进化变异。母婴对之间的系统发育分析表明，一个单一的母体变异的传播发生，除了一个样本对。当评估克隆PCR产物的氨基酸序列时，非传播母亲似乎具有比传播母亲（p=0.0410）和感染婴儿（p=0.0315）更多的不同序列。复制动力学分析表明，在感染后12天（p=0.0434）和感染后15天（p=0.0181），在GHOST CCR 5细胞培养物中，递质表现出更快的复制动力学。总之，病毒同质性和快速复制动力学与垂直传播相关。
HIV-1 vertical transmission in Puerto Rico has decreased significantly due to the implementation of antiviral therapy. Several studies have shown that the phenotype of the HIV-1 isolates initially recovered from infected infants has generally been one that replicates rapidly, infects macrophages, and preferentially use the CCR5 coreceptor. Our hypothesis is that viral genotypic and phenotypic differences exist between HIV-1 nontransmitter and transmitter mothers. Viral DNA samples and virus isolates were analyzed from a Puerto Rican perinatal population. Heteroduplex tracking assay (HTA) was performed on DNA samples to detect env V3 evolutionary variants and the extent of heterogeneity within each sample. HIV-1 C2-V3 variants were cloned from each patient to study sequence variation among the groups. Differences in replication kinetics of viral isolates in macrophage and GHOST CCR5 cells were analyzed by use of repeated measures linear regression analysis. HTA analysis showed that only two nontransmitter patient samples showed the presence of evolutionary variants. Phylogenetic analysis between maternal-infant pairs showed that transmission of a single maternal variant occurred, with the exception of one sample pair. When evaluating amino acid sequences from cloned PCR products, nontransmitting mothers appear to have a higher number of distinct sequences than both the transmitting mothers (p=0.0410) and the infected infants (p=0.0315). Analysis of replication kinetics indicated that transmitters showed faster replication kinetics in GHOST CCR5 cell cultures at 12 days postinfection (p=0.0434) and 15 days postinfection (p=0.0181). In conclusion, viral homogeneity and rapid replication kinetics were correlated with vertical transmission.