Human T-cell leukemia virus type 1 infects multiple lineage hematopoietic cells in vivo
| العنوان: | Human T-cell leukemia virus type 1 infects multiple lineage hematopoietic cells in vivo |
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| المؤلفون: | Ki Ryang Koh, Mohamed Mahmoud Ahmed Mahgoub, Hirofumi Akari, Yusuke Higuchi, Charles R. M. Bangham, Masao Matsuoka, Takaharu Ueno, Anat Melamed, Jun-ichi Fujisawa, Masakazu Shimizu, Akatsuki Saito, Norihiro Takenouchi, Kenji Sugata, Jun-ichirou Yasunaga, Fumihiko Matsuda, Michi Miura, Rie Furuta |
| المساهمون: | Medical Research Council (MRC) |
| المصدر: | PLoS Pathogens PLoS Pathogens, Vol 13, Iss 11, p e1006722 (2017) |
| بيانات النشر: | The Public Library of Science, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | RNA viruses, 0301 basic medicine, Neutrophils, viruses, Cellular differentiation, CD8-Positive T-Lymphocytes, Pathology and Laboratory Medicine, Monocytes, White Blood Cells, 0302 clinical medicine, Animal Cells, 1108 Medical Microbiology, immune system diseases, Medicine and Health Sciences, Cytotoxic T cell, Biology (General), Cells, Cultured, Human T-lymphotropic virus 1, T Cells, virus diseases, Cell Differentiation, Gene Products, tax, Leukemia, Haematopoiesis, medicine.anatomical_structure, Medical Microbiology, 1107 Immunology, Viral Pathogens, 030220 oncology & carcinogenesis, Viruses, Pathogens, Cellular Types, Stem cell, Research Article, 0605 Microbiology, QH301-705.5, Immune Cells, Immunology, Cytotoxic T cells, Bone Marrow Cells, Biology, Research and Analysis Methods, Microbiology, Virus, 03 medical and health sciences, Virology, Retroviruses, Genetics, medicine, Animals, Humans, Molecular Biology Techniques, Microbial Pathogens, Molecular Biology, Blood Cells, Biology and life sciences, Organisms, Htlv-1, Cell Biology, RC581-607, Hematopoietic Stem Cells, medicine.disease, HTLV-I Infections, Macaca mulatta, 030104 developmental biology, Parasitology, Bone marrow, Immunologic diseases. Allergy, CD8, Cloning, Developmental Biology |
| الوصف: | Human T-cell leukemia virus type 1 (HTLV-1) infects mainly CD4+CCR4+ effector/memory T cells in vivo. However, it remains unknown whether HTLV-1 preferentially infects these T cells or this virus converts infected precursor cells to specialized T cells. Expression of viral genes in vivo is critical to study viral replication and proliferation of infected cells. Therefore, we first analyzed viral gene expression in non-human primates naturally infected with simian T-cell leukemia virus type 1 (STLV-1), whose virological attributes closely resemble those of HTLV-1. Although the tax transcript was detected only in certain tissues, Tax expression was much higher in the bone marrow, indicating the possibility of de novo infection. Furthermore, Tax expression of non-T cells was suspected in bone marrow. These data suggest that HTLV-1 infects hematopoietic cells in the bone marrow. To explore the possibility that HTLV-1 infects hematopoietic stem cells (HSCs), we analyzed integration sites of HTLV-1 provirus in various lineages of hematopoietic cells in patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and a HTLV-1 carrier using the high-throughput sequencing method. Identical integration sites were detected in neutrophils, monocytes, B cells, CD8+ T cells and CD4+ T cells, indicating that HTLV-1 infects HSCs in vivo. We also detected Tax protein in myeloperoxidase positive neutrophils. Furthermore, dendritic cells differentiated from HTLV-1 infected monocytes caused de novo infection to T cells, indicating that infected monocytes are implicated in viral spreading in vivo. Certain integration sites were re-detected in neutrophils from HAM/TSP patients at different time points, indicating that infected HSCs persist and differentiate in vivo. This study demonstrates that HTLV-1 infects HSCs, and infected stem cells differentiate into diverse cell lineages. These data indicate that infection of HSCs can contribute to the persistence and spread of HTLV-1 in vivo. Author summary HTLV-1 primarily infects peripheral CD4+CCR4+CADM1+ T cells in vivo. In this study, we show that HTLV-1 infects HSCs, which differentiate into multiple lineages of hematopoietic cells, and likely act as viral reservoir, giving rise to infected neutrophils, monocytes and B cells. Infected monocytes are thought to spread virus in vivo. Infected T cells in the periphery are chimeric in origin: T cells newly infected in the periphery, and infected T cells differentiated from infected HSCs. This observation suggests that viral genes such as HBZ and tax are responsible for converging the molecular differentiation program into a single direction with the characteristic immunophenotype associated with the expression of CCR4 and CADM1. It has been believed that HTLV-1 infects target cells in the periphery. However, this study reveals a new strategy of HTLV-1 spreading in vivo. These findings have implications for understanding of HTLV-1 pathogenesis as well as treatment of HTLV-1 associated diseases. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1553-7366 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0b78ac0efffc164c2bf10388e31390d0Test http://hdl.handle.net/2298/41365Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0b78ac0efffc164c2bf10388e31390d0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537366 |
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