HTLV-1 targets human placental trophoblasts in seropositive pregnant women
Kenta Tezuka, … , Kiyonori Miura, Isao Hamaguchi
Kenta Tezuka, … , Kiyonori Miura, Isao Hamaguchi
Published October 19, 2020
Citation Information: J Clin Invest. 2020;130(11):6171-6186. https://doi.org/10.1172/JCI135525.
View: Text | PDF
Research Article Infectious disease Virology

HTLV-1 targets human placental trophoblasts in seropositive pregnant women

Abstract

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.

Authors

Kenta Tezuka, Naoki Fuchi, Kazu Okuma, Takashi Tsukiyama, Shoko Miura, Yuri Hasegawa, Ai Nagata, Nahoko Komatsu, Hiroo Hasegawa, Daisuke Sasaki, Eita Sasaki, Takuo Mizukami, Madoka Kuramitsu, Sahoko Matsuoka, Katsunori Yanagihara, Kiyonori Miura, Isao Hamaguchi

×

Figure 1

Comparative analysis of HTLV-1 proviral load in pregnant HTLV-1 carriers.

Options: View larger image (or click on image) Download as PowerPoint
Comparative analysis of HTLV-1 proviral load in pregnant HTLV-1 carriers...
HTLV screening tests for 254 pregnant HTLV-1 carriers were performed during the second trimester of pregnancy. All donors were serologically positive for HTLV-1 infection. Each dot in the dot plots and scatterplots indicates the HTLV-1 proviral load (PVL) of a single specimen. (A) Detection of HTLV-1 in, and differences in PVL between, maternal blood, placental villous tissue, and cord blood in 254 seropositive women. (B) Comparison of maternal blood PVL among 248 pregnant carriers with PVL in the maternal blood, who were distinguished by proviral DNA detection in the placental villous tissue and/or in the cord blood. In A and B, bold lines indicate the median values of PVL. The P values were calculated with Kruskal-Wallis test followed by Dunn’s multiple-comparisons test. (C–E) Correlation analysis of the PVL was performed. Spearman’s rank correlation test was used to identify statistically significant correlations between values. A positive correlation was detected between PVL in the placental villous tissue and PVL in the maternal blood of 140 pregnant HTLV-1 carriers in whom provirus was detected in the placental villous tissue (C). A nonsignificant correlation was observed between cord blood PVL and maternal blood PVL (D) or placental villous PVL (E) for the 6 pregnant HTLV-1 carriers in whom provirus was detected in the cord blood. (F) Representative electrophoretogram of 6 independent experiments of microsatellite genotyping using short tandem repeat (STR) markers. STR loci of the maternal blood were distinct from those of fetal tissues derived from the same specimen. Amelogenin confirmed the presence of the X chromosome–specific allele alone in the maternal blood, and the X and Y chromosome–specific alleles in the placental villous tissue and the cord blood.