HTLV-1 targets human placental trophoblasts in seropositive pregnant women

• Published in: The Journal of clinical investigation Vol. 130; no. 11; pp. 6171 - 6186
• Main Authors: Tezuka, Kenta, Fuchi, Naoki, Okuma, Kazu, Tsukiyama, Takashi, Miura, Shoko, Hasegawa, Yuri, Nagata, Ai, Komatsu, Nahoko, Hasegawa, Hiroo, Sasaki, Daisuke, Sasaki, Eita, Mizukami, Takuo, Kuramitsu, Madoka, Matsuoka, Sahoko, Yanagihara, Katsunori, Miura, Kiyonori, Hamaguchi, Isao
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.11.2020
• Subjects: Adult; Antibodies; Antigens; Biomedical research; Breast feeding; Breast milk; Breastfeeding & lactation; Cells, Cultured; Cord blood; Deoxyribonucleic acid; Development and progression; Disease transmission; DNA; Female; Fetuses; Food contamination & poisoning; Health aspects; HTLV-I infections; HTLV-I Infections - metabolism; HTLV-I Infections - pathology; HTLV-I Infections - transmission; Human T-lymphotropic virus 1 - metabolism; Humans; Infections; Infectious Disease Transmission, Vertical; Leukemia; Lymphocytes; Lymphocytes T; Maternal-fetal exchange; Perinatal infection; Placenta; Pregnancy; Pregnancy Complications, Infectious - metabolism; Pregnancy Complications, Infectious - pathology; Pregnancy Complications, Infectious - virology; Ribonucleic acid; RNA; Trophoblasts; Trophoblasts - metabolism; Trophoblasts - pathology; Trophoblasts - virology; Uterus; Viral infections; Viral research; Womens health; Japan; Infectious disease; Epidemiology; Virology
• ISSN: 0021-9738; 1558-8238; 1558-8238
• DOI: 10.1172/JCI135525

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.