Ometto L, Zanotto C, Maccabruni A, Caselli D, Truscia D, Giaquinto C, Ruga E, Chieco-Bianchi L, De Rossi A
Institute of Oncology, University of Padova, Italy.
AIDS. 1995 May;9(5):427-34.
To investigate the role of maternal HIV-1 isolate phenotype and a child's cell susceptibility/resistance to viral infection in mother-to-child HIV-1 transmission.
Forty-nine women were studied at the time of delivery. Primary isolates, obtained by culturing patient peripheral blood mononuclear cells (PBMC) with PBMC from healthy donors, were characterized for tropism and syncytium-inducing capability in monocyte-derived macrophages (MDM), peripheral blood lymphocytes (PBL), and in the MT-2 and MOLT-3 T-cell lines.
Seven women transmitted HIV-1 to their children. Primary isolates were obtained from six and 28 transmitting and non-transmitting mothers, respectively. All primary isolates from transmitting mothers and their infants but only 50% of those from non-transmitting mothers replicated in MDM, regardless of their replication capacity in T-cell lines. PBL and MDM cells from six uninfected children were exposed to the corresponding maternal isolates. Polymerase chain reaction analysis of HIV-1 DNA in cells and p24 antigen assay in culture supernatants disclosed that two PBL and five MDM cultures were resistant to viral infection; two other PBL cultures, although HIV-1-infected, were negative for p24 production. Depletion of CD8+ cells only partially restored productive infection in CD4+ cell cultures. Moreover, all six PBL but only one MDM cultures were productively infected by an isolate obtained from a transmitting mother, thus suggesting that MDM resistance to HIV-1 infection is not viral isolate-restricted.
Our findings strongly suggest that mother-to-child HIV-1 transmission is influenced by both monocyte-macrophage tropism of the maternal isolate and susceptibility of the child's target cells, in particular monocyte-macrophages, to HIV-1 infection.
研究母亲HIV-1分离株表型及儿童细胞对病毒感染的易感性/抗性在母婴HIV-1传播中的作用。
对49名产妇进行了研究。通过将患者外周血单个核细胞(PBMC)与健康供体的PBMC共同培养获得的原始分离株,在单核细胞衍生的巨噬细胞(MDM)、外周血淋巴细胞(PBL)以及MT-2和MOLT-3 T细胞系中进行嗜性和诱导合胞体能力的鉴定。
7名女性将HIV-1传播给了她们的孩子。分别从6名和28名有传播和无传播的母亲中获得了原始分离株。来自有传播的母亲及其婴儿的所有原始分离株,但来自无传播的母亲的原始分离株中只有50%能在MDM中复制,无论它们在T细胞系中的复制能力如何。将6名未感染儿童的PBL和MDM细胞暴露于相应的母亲分离株。对细胞中HIV-1 DNA的聚合酶链反应分析以及培养上清液中的p24抗原检测表明,2个PBL培养物和5个MDM培养物对病毒感染具有抗性;另外2个PBL培养物虽然感染了HIV-1,但p24产生呈阴性。CD8+细胞的去除仅部分恢复了CD4+细胞培养物中的有效感染。此外,所有6个PBL培养物,但只有1个MDM培养物被从有传播的母亲中获得的分离株有效感染,因此表明MDM对HIV-1感染的抗性不受病毒分离株限制。
我们的研究结果强烈表明,母婴HIV-1传播受母亲分离株的单核细胞-巨噬细胞嗜性以及儿童靶细胞,特别是单核细胞-巨噬细胞对HIV-1感染的易感性的影响。