HTLV-1 targets human placental trophoblasts in seropositive pregnant women
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
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
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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

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Figure 4

Detection of HTLV-1 plus-strand mRNAs in pregnant carrier–derived placental villous tissues.

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Detection of HTLV-1 plus-strand mRNAs in pregnant carrier–derived placen...
RNA ISH with HTLV-1–specific probes targeting plus-strand mRNAs was used to stain the placental villous tissue sections of pregnant HTLV-1 carriers. The carriers were identical to those listed in Table 2. (A) ISH results are shown for each group of pregnant carriers (nos. 1, 9, and 16), and for a pregnant chronic ATL patient (no. 19). Viral mRNA was detected using DAB chromogen (brown). Boxes indicate regions shown at a higher magnification in adjacent lower panels. Data are representative of at least 5 nonserial tissue sections. Scale bars in lower and higher magnifications represent 200 μm and 50 μm, respectively. (B) Quantitative evaluation of ISH results. The total number of pX probe–positive foci in stained sections was counted by microscopy. Data are expressed as the mean ± SD from 5 nonserial tissue sections. The Mann-Whitney U test was performed to compare statistical differences between groups in subjects with HTLV-1–negative and –positive cord blood samples (nos. 7–12 vs. nos. 13–18).