Persistent Human T‐Lymphotropic Virus Type 1 (HTLV‐1) Infection in the Placenta of Pregnant Women
Mother-to-child transmission (MTCT) is the primary route of human T-lymphotropic virus type 1 (HTLV-1) infection. Although formula feeding reduces breastfeeding-associated transmission, MTCT still occurs, implicating pregnancy or delivery as key transmission windows. In this study, placental tissues from nine HTLV-1-positive mothers were analyzed using DNA/RNAscope, revealing low HTLV-1 DNA and RNA levels and a low RNA/DNA ratio, consistent with latent infection in the placenta and potentially explaining the low MTCT rate. Elevated interferon (IFN)-β levels were observed in infected placentas compared to seronegative controls, while IFNα, IFNγ, and IFITM expression remained unchanged. Concurrently, sustained IFNβ expression in infected placentas suggests its dual roles in HTLV-1 pathogenesis: suppressing viral replication while potentially disrupting placental homeostasis through chronic inflammation. In vitro modeling using BeWo cells or primary trophoblasts cocultured with HTLV-1-infected MT-2 cells demonstrated syncytin-1-mediated viral entry, confirmed by HTLV-1 p19 detection in both trophoblasts. Of note, HTLV-1 transmission was abolished by a syncytin-1-specific fusion inhibitor HRB1, underscoring syncytin-1's essential role in cell-to-cell transmission of HTLV-1. Thus, this study identifies syncytin-1 as a therapeutic target to block vertical transmission and highlights the need to balance antiviral responses with placental integrity in HTLV-1 management.
Authors
- Jerusa Smid (ORCID: https://orcid.org/0000-0001-9513-0964)
- Jorge Casseb (ORCID: https://orcid.org/0000-0002-4553-2559)
- Jacielma De Oliveira Freire (ORCID: https://orcid.org/0000-0002-4586-8087)
- Sandy Vieira Teixeira (ORCID: https://orcid.org/0000-0003-0743-8972)
- Michel E. Haziot (ORCID: https://orcid.org/0000-0002-3549-1992)
- Tatiane Assone (ORCID: https://orcid.org/0000-0003-0993-4523)
- George M. P. R. Souza (ORCID: https://orcid.org/0000-0003-4678-6910)
- Rosa Maria Nascimento Marcusso (ORCID: https://orcid.org/0000-0002-8396-0263)
- Carlos Fernando Apoliano (ORCID: https://orcid.org/0000-0002-3963-7661)
- Víctor Ângelo Folgosi (ORCID: https://orcid.org/0000-0002-0114-7587)
- Augusto César Penalva de Oliveira (ORCID: https://orcid.org/0000-0002-4084-7973)
- Gabriela Prates (ORCID: https://orcid.org/0000-0003-3728-9621)
- Guochun Jiang (ORCID: https://orcid.org/0000-0003-1911-5089)
- Yuyang Tang
- Xiaoyi Li (ORCID: https://orcid.org/0000-0002-3725-259X)
- Hongjie Chen (ORCID: https://orcid.org/0000-0003-3139-5706)
- Fernanda Grassi
Institutions
- University of North Carolina at Chapel Hill (US)
- Universidade Federal da Bahia (BR)
- Instituto de Infectologia Emílio Ribas (BR)
- Fundação Faculdade de Medicina (BR)
- University of North Carolina System (US)
- Fundação Oswaldo Cruz (BR)
- Universidade Federal de São Paulo (BR)
Publication Details
- Journal
- Journal of Medical Virology
- Published
- 2025-09-01
- DOI
- https://doi.org/10.1002/jmv.70585
- Citations
- 1
- Primary Topic
- T-cell and Retrovirus Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.80
Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- National Institute of Mental Health
- National Institute of Allergy and Infectious Diseases