Placental trophoblasts resist infection by multiple human immunodeficiency virus (HIV) type 1 variants even with cytomegalovirus coinfection but support HIV replication after provirus transfection
Placental trophoblasts resist infection by multiple human immunodeficiency virus (HIV) type 1 variants even with cytomegalovirus coinfection but support HIV replication after provirus transfection
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DOI：
10.1128/jvi.71.9.6359-6372.1997
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发表时间：
1997-09-01
影响因子：
5.4
通讯作者：
Guilbert, LJ
中科院分区：
文献类型：
--
作者：
Kilani, RT;Chang, LJ;Guilbert, LJ
无细胞人类免疫缺陷病毒1型（HIV-1）能否感染胎盘滋养层细胞（这反过来又可能将病毒传播到胎儿循环中）是有争议的，但对于评估替代途径至关重要（如细胞介导的感染或滋养层损伤），我们已经解决了感染因素，如细胞纯度，来源，培养方法，和激活状态以及病毒变体和检测方法，以最终确定游离病毒攻击滋养层的结果。来自11个不同胎盘的滋养层的纯（> 99.98%）群体在高达6的感染复数（MOI）下用五种不同的HIV-1变体进行攻击，其中三种是来自感染婴儿的非合胞体形成的嗜巨噬细胞分离物，有和没有合并感染Vith巨细胞病毒;通过5种不同的标准监测这些制剂在攻击后长达3周的生产性感染，其中最敏感的是与靶细胞共培养，可以在10（-7）的MOI下检测病毒，以及HIV DNA PCR，每10（5）个细胞检测到30个病毒拷贝，从未检测到感染，然而，分子克隆的T细胞（pNL 4 -3）和巨噬细胞（pNL（AD 8））嗜性前病毒质粒，当转染到原代滋养层中时，产生生产性感染，表明滋养层不抑制晚期病毒复制和装配。由于滋养层制备物的纯度，感染培养期的延长，滋养层制备物的数量和检测的病毒类型，生物测定和分子检测测定的灵敏度以及滋养层不能支持来自原病毒的病毒复制的观察，本研究的结果有力地证明游离病毒不能感染原代绒毛滋养层。
Whether cell-free human immunodeficiency virus type 1 (HIV-1) can productively infect placental trophoblasts (which in turn could transmit the virus into the fetal circulation) is controversial but essential to know for the evaluation of alternative routes (such as cell-mediated infection or trophoblast damage), We have addressed infection factors such as cell purity, source, culture methods, and activation states as well as virus variant and detection methods to conclusively determine the outcome of trophoblast challenge by free virus. Pure (>99,98%) populations of trophoblasts from 11 different placentas were challenged at a multiplicity of infection (MOI) as high as 6 with five different HIV-1 variants, three of which are non-syncytium-forming, macrophage-tropic isolates from infected infants, with and, without coinfection,vith cytomegalovirus; these preparations were monitored for productive infection for up to 3 weeks after challenge by five different criteria, the most sensitive of which were cocultivation with target cells that can detect virus at an MOI of 10(-7) and HIV DNA PCR that detects 30 virus copies per 10(5) cells, Infection was never detected, However, molecularly cloned T-cell (pNL4-3)-and macrophage (pNL(AD8))-tropic provirus plasmids, when transfected into primary trophoblasts, yielded productive infections, indicating that trophoblasts do not suppress late-stage virus replication and assembly, Because of the purity of the trophoblast preparations, the extended length of the infection culture period, the number of trophoblast preparations and virus types examined, the sensitivity of the bioassays and molecular detection assays, and the observations that trophoblasts tan support virus replication from provirus, the results of this study strongly argue that free virus cannot infect primary villous trophoblasts.