HTLV-1 targets human placental trophoblasts in seropositive pregnant women
HTLV-1 targets human placental trophoblasts in seropositive pregnant women
复制标题
DOI：
10.1172/jci135525
复制
发表时间：
2020-11-02
影响因子：
15.9
通讯作者：
Hamaguchi, Isao
中科院分区：
文献类型：
--
作者：
Tezuka, Kenta;Fuchi, Naoki;Hamaguchi, Isao
人类T细胞白血病病毒1型（HTLV-1）主要通过母乳垂直传播。通过配方奶喂养的母婴传播率（MTCT）虽然显著低于母乳喂养，但约为2.4%-3.6%，表明可能存在其他传播途径。HTLV-1的MTCT可能通过子宫、产道或胎盘组织发生；后者被称为经胎盘传播。在这里，我们发现HTLV-1前病毒DNA存在于近一半怀孕携带者胎儿的胎盘绒毛组织和少数脐带血样本中。RNA ISH分析显示，几乎所有htlv -1阳性的胎盘绒毛组织中都存在htlv -1表达细胞，并且在脐带血样本中htlv -1阳性的受试者中其频率显著更高。此外，胎盘绒毛滋养细胞表达HTLV-1受体，并表现出对HTLV-1感染的易感性增加。此外，htlv -1感染的滋养细胞表达高水平的病毒抗原，并在人源化小鼠模型中促进靶T细胞的从头感染。综上所述，HTLV-1携带者妊娠期间HTLV-1在胎盘绒毛组织中高表达，绒毛滋养细胞对HTLV-1表现出较高的敏感性，提示HTLV-1的MTCT是通过胎盘发生的。
Human T cell leukemia virus type 1 (HTLV-1) is mainly transmitted vertically through breast milk. The rate of mother-to-child transmission (MTCT) through formula feeding, although significantly lower than through breastfeeding, is approximately 2.4%-3.6%, suggesting the possibility of alternative transmission routes. MTCT of HTLV-1 might occur through the uterus, birth canal, or placental tissues; the latter is known as transplacental transmission. Here, we found that HTLV-1 proviral DNA was present in the placental villous tissues of the fetuses of nearly half of pregnant carriers and in a small number of cord blood samples. An RNA ISH assay showed that HTLV-1-expressing cells were present in nearly all subjects with HTLV-1-positive placental villous tissues, and their frequency was significantly higher in subjects with HTLV-1-positive cord blood samples. Furthermore, placental villous trophoblasts expressed HTLV-1 receptors and showed increased susceptibility to HTLV-1 infection. In addition, HTLV-1-infected trophoblasts expressed high levels of viral antigens and promoted the de novo infection of target T cells in a humanized mouse model. In summary, during pregnancy of HTLV-1 carriers, HTLV-1 was highly expressed in placental villous tissues, and villous trophoblasts showed high HTLV-1 sensitivity, suggesting that MTCT of HTLV-1 occurs through the placenta.