In vivo dynamics and adaptation of HTLV-1-infected clones under different clinical conditions
| العنوان: | In vivo dynamics and adaptation of HTLV-1-infected clones under different clinical conditions |
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| المؤلفون: | Charles R. M. Bangham, Masao Matsuoka, Anat Melamed, Kisato Nosaka, Jun-ichirou Yasunaga, Yasuhiko Sugawara, Hayato Utsunomiya, Takafumi Shichijo, Yukihiro Inomata, Asami Yamada, Hirofumi Akari, Mikiko Izaki, Kenji Sugata, Youko Suehiro, Taizo Hibi |
| المصدر: | PLoS Pathogens, Vol 17, Iss 2, p e1009271 (2021) PLoS Pathogens |
| بيانات النشر: | Public Library of Science (PLoS), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, RNA viruses, Physiology, T-Lymphocytes, Artificial Gene Amplification and Extension, CD8-Positive T-Lymphocytes, Monkeys, Virus Replication, Pathology and Laboratory Medicine, Biochemistry, Polymerase Chain Reaction, White Blood Cells, 0302 clinical medicine, Proviruses, Animal Cells, Immune Physiology, Medicine and Health Sciences, Leukemia-Lymphoma, Adult T-Cell, Cytotoxic T cell, Biology (General), Immune Response, Mammals, Human T-lymphotropic virus 1, 0303 health sciences, Immune System Proteins, biology, T Cells, Hematopoietic Stem Cell Transplantation, Eukaryota, Gene Products, tax, Middle Aged, Viral Load, Provirus, Leukemia, Medical Microbiology, Viral Pathogens, 030220 oncology & carcinogenesis, Viruses, Vertebrates, Female, Pathogens, Cellular Types, Antibody, Macaque, Research Article, Adult, Primates, QH301-705.5, Immune Cells, Immunology, Cytotoxic T cells, Research and Analysis Methods, Microbiology, Antibodies, Virus, Macaca fuscata, 03 medical and health sciences, Immune system, Antigen, Virology, Retroviruses, Old World monkeys, Genetics, medicine, Animals, Humans, Molecular Biology Techniques, Microbial Pathogens, Molecular Biology, 030304 developmental biology, Blood Cells, Organisms, Biology and Life Sciences, Proteins, Dendritic Cells, Htlv-1, Cell Biology, RC581-607, medicine.disease, HTLV-I Infections, Clone Cells, Liver Transplantation, Amniotes, biology.protein, Natural Killer T-Cells, Parasitology, Immunologic diseases. Allergy, Zoology, CD8, Cloning |
| الوصف: | Human T-cell leukemia virus type 1 (HTLV-1) spreads through cell contact. Therefore, this virus persists and propagates within the host by two routes: clonal proliferation of infected cells and de novo infection. The proliferation is influenced by the host immune responses and expression of viral genes. However, the detailed mechanisms that control clonal expansion of infected cells remain to be elucidated. In this study, we show that newly infected clones were strongly suppressed, and then stable clones were selected, in a patient who was infected by live liver transplantation from a seropositive donor. Conversely, most HTLV-1+ clones persisted in patients who received hematopoietic stem cell transplantation from seropositive donors. To clarify the role of cell-mediated immunity in this clonal selection, we suppressed CD8+ or CD16+ cells in simian T-cell leukemia virus type 1 (STLV-1)-infected Japanese macaques. Decreasing CD8+ T cells had marginal effects on proviral load (PVL). However, the clonality of infected cells changed after depletion of CD8+ T cells. Consistent with this, PVL at 24 hours in vitro culture increased, suggesting that infected cells with higher proliferative ability increased. Analyses of provirus in a patient who received Tax-peptide pulsed dendritic cells indicate that enhanced anti-Tax immunity did not result in a decreased PVL although it inhibited recurrence of ATL. We postulate that in vivo selection, due to the immune response, cytopathic effects of HTLV-1 and intrinsic attributes of infected cells, results in the emergence of clones of HTLV-1-infected T cells that proliferate with minimized HTLV-1 antigen expression. Author summary HTLV-1 spreads in vivo through two routes: de novo infection and clonal proliferation of infected cells. Reverse transcriptase inhibitors and integrase inhibitors do not influence the PVL in HTLV-1-infected individuals, indicating that clonal proliferation is dominant to maintain and increase PVL in vivo in the chronic phase. It is assumed that the host immune responses are critical factors for clonal proliferation. We found that HTLV-1-infected clones dramatically changed during de novo infection whereas the clones in the chronic phase survived long-term after transplantation, indicating that HTLV-1-infected clones are selected for survival in vivo. Surprisingly, depletion of CD8+ cells had a small impact on PVL in a STLV-1 infected Japanese macaque, but modified the clonality of infected cells. The cells after depletion of CD8+ cells showed a higher proliferative activity during short-term in vitro culture. This study reveals that intrinsic attributes of selected clones contribute to clonal proliferation of infected cells. |
| اللغة: | English |
| تدمد: | 1553-7374 1553-7366 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b3c50ded3eeb2091998a044bbb97260cTest https://doaj.org/article/aa6ab0195b1d47f492253da164ea1e2fTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b3c50ded3eeb2091998a044bbb97260c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537374 15537366 |
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