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In vivo dynamics and adaptation of HTLV-1-infected clones under different clinical conditions
Open accessAbstract
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.
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Animal models can provide information about HTLV-1 replication and virus-associated disease progression.
“Some mechanisms of HTLV-1 replication and virus-associated disease progression can be learnt from animal models [44,122,136,137].”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [137]
The Results section (page not available in our copy) uses STLV-1-infected Japanese macaques to investigate how immune responses affect infected-cell clonality, supporting the claim that animal models can inform viral propagation mechanisms. It does not report virus-associated disease progression in the macaques, so that part of the claim is not supported by this paper. (LLM, conf=0.82)
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Metadata
- Authors
- Izaki, M., Yasunaga, J.-I., Nosaka, K., Sugata, K., Utsunomiya, H., Suehiro, Y., Shichijo, T., Yamada, A., Sugawara, Y., Hibi, T., Inomata, Y., Akari, H., Melamed, A., Bangham, C., & Matsuoka, M.
- Affiliations
- Kumamoto University (JP)
- Kyoto University (JP)
- National Hospital Organization Kyushu Cancer Center (JP)
- Imperial College London (GB)
- Corresponding author
- Matsuoka, Masao
- ORCID
- Venue
- PLOS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2021-02-01
- Volume
- 17
- Issue
- 2
- Pages
- e1009271
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC7877780
- OpenAlex
- W3126941418
- Cited by
- 15
- References
- 50
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 5 · 2022: 1 · 2021: 2
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Update notices
- new_version (2021-02-11)
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Kumamoto University Repository (Kumamoto University) (submittedVersion, cc-by-nc-nd)
- Funders
- Project for Cancer Research And Therapeutic Evolution (20cm0106306h0005)
- Research Program on Emerging and Re-emerging Infectious Diseases (20fk0108088h0002)
- Japan Agency for Medical Research and Development /JSPS (19H03689, 20H03514)
- JSPS Core-to-Core Program A, Advanced Research Networks
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
- Keywords
- HTLV-1, clonal selection, proviral load, cell-mediated immunity, CD8+ T cells, CD16+ natural killer cells, liver transplantation, hematopoietic stem cell transplantation, STLV-1, Japanese macaque, dendritic cell vaccination, adult T-cell leukemia/lymphoma, viral persistence, clonality
- MeSH terms
- Macaca fuscata, Adult, Animals, Clone Cells, Dendritic Cells, Female, Humans, Male, Middle Aged, Proviruses, T-Lymphocytes, Virus Replication, Human T-lymphotropic virus 1, Leukemia-Lymphoma, Adult T-Cell, HTLV-I Infections, Liver Transplantation, Gene Products, tax, Hematopoietic Stem Cell Transplantation, CD8-Positive T-Lymphocytes, Viral Load, Natural Killer T-Cells
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