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 3

Development of a plus- and minus-strand HTLV-1 mRNA–specific RNAscope ISH assay using a humanized mouse model.

Options: View larger image (or click on image) Download as PowerPoint
Development of a plus- and minus-strand HTLV-1 mRNA–specific RNAscope IS...
(A) Schematic drawing of the experimental schedule is shown. All NOJ mice were reconstituted with a human immune system by the intrahepatic transplantation of human CD133+ hematopoietic stem cells into newborn mice. The mice were inoculated orally with HTLV-1–infected MT-2 cells at 0 days postinfection (dpi) and were sacrificed at 63 dpi (arrows). Arrowheads indicate the time points of blood collection. (B and C) RNA ISH with HTLV-1–specific probes targeting plus-strand mRNAs (B) and minus-strand mRNAs (C) was used to stain the spleen and lymph node sections of mock- or HTLV-1–infected humanized mice. Viral mRNAs were detected using DAB chromogen (brown). Boxes indicate regions shown at a higher magnification in adjacent lower panels. Data are representative of at least 3 nonserial tissue sections. Scale bars in lower and higher magnifications represent 500 μm and 100 μm, respectively.