Farzin Azadeh, Boyer Pamela, Ank Bonnie, Nielsen-Saines Karin, Bryson Yvonne
Department of Pediatrics, Division of Pediatric Infectious Diseases, University of California Los Angeles, Los Angeles, CA 90095-1752, USA.
AIDS Res Hum Retroviruses. 2013 Jan;29(1):77-83. doi: 10.1089/AID.2011.0355. Epub 2012 Dec 7.
Indirect evidence suggests that amniotic fluid (AF) may play a role in the pathogenesis of in utero HIV-1 transmission. The purpose of this study was to evaluate the potential innate inhibitory role of AF on HIV replication, which may contribute to protection of the fetus against intrauterine transmission. AF was collected from term HIV-1-negative women undergoing scheduled cesarean section. The inhibitory effect of AF against HIV-1(BA-L) replication was tested in vitro with or without the addition of protease inhibitor cocktail (PIC) in PHA-stimulated PBMC cultures. Quantitative measurement of human neutrophil peptides 1-3 (HNP1-3) was performed on all AF samples, using an ELISA assay. AF exhibited a dose-dependent inhibitory activity against HIV-1(BA-L) replication, with all samples (n=12) reaching significant inhibitory effect using 50% AF. In vitro, this activity decreased over time, but was able to be sustained with the addition of PIC. The HNP1-3 concentration in AF samples (n=12) ranged from undetectable (<41 pg/ml, n=3) to >250,000 pg/ml with a median of 5,146 pg/ml. AF exhibited a significant and dose-dependent innate inhibitory activity against HIV-1 replication, which was present in all AF samples tested. This effect was prolonged in the presence of PIC, suggesting that the inhibitory factor was in the cell-free protein fraction. The HNP1-3 concentration in AF was in the subinhibitory range for HIV with no correlation between its concentration and the HIV-1 inhibitory activity. These data show the presence of a significant innate inhibitory activity against HIV in AF.
间接证据表明，羊水（AF）可能在子宫内HIV-1传播的发病机制中起作用。本研究的目的是评估羊水对HIV复制的潜在先天性抑制作用，这可能有助于保护胎儿免受宫内传播。羊水取自接受择期剖宫产的足月HIV-1阴性妇女。在PHA刺激的PBMC培养物中，在添加或不添加蛋白酶抑制剂混合物（PIC）的情况下，体外测试羊水对HIV-1（BA-L）复制的抑制作用。使用ELISA测定法对所有羊水样本进行人中性粒细胞肽1-3（HNP1-3）的定量测量。羊水对HIV-1（BA-L）复制表现出剂量依赖性抑制活性，所有样本（n = 12）使用50%羊水时均达到显著抑制效果。在体外，这种活性随时间下降，但添加PIC后能够维持。羊水样本（n = 12）中的HNP1-3浓度范围从检测不到（<41 pg/ml，n = 3）到>250,000 pg/ml，中位数为5,146 pg/ml。羊水对HIV-1复制表现出显著的剂量依赖性先天性抑制活性，在所测试的所有羊水样本中均存在。在PIC存在的情况下，这种作用会延长，表明抑制因子存在于无细胞蛋白质部分。羊水中HNP1-3的浓度处于对HIV的亚抑制范围内，其浓度与HIV-1抑制活性之间无相关性。这些数据表明羊水中存在针对HIV的显著先天性抑制活性。
