Clonal proliferation of HTLV-1-infected cells is associated with spontaneous malignant tumor formation in mice
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Adult T-cell leukemia/lymphoma (ATL) is characterized by monoclonal proliferation of tumor cells that harbor integrated human T-cell leukemia virus type-1 (HTLV-1). These malignant cells accumulate in various organs including the liver, spleen and skin in addition to blood and lymph nodes. Although there have been several reports of animal models of HTLV-1 infection in which proviral distribution has been examined, clonal expansion of the experimentally infected host cells has not been extensively analyzed. Here we provide experimental evidence that clonal proliferation of the infected host cells occurs in the spleen for more than one year. During a 15 month period of persistent infection, two out of ten mice developed spontaneous tumors. Although the tumors were not ATL-like, cells exhibiting mono- or oligoclonal proliferation and having the same site of HTLV-1 integration were identified in tumor tissues as well as in the spleen. Quantitative analysis of the cells belonging to each cell clone suggested that these proliferating cell clones were associated with the tumors and that spontaneous tumor tissues might provide a suitable microenvironment for proliferation and accumulation of infected cell clones at the late stage of infection.
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Immunocompetent HTLV-1 carrier mouse models demonstrate very little in vivo spread of infection with no evidence of disease, except for one report of tumorigenesis.
“A caveat, however, is that immunocompetent HTLV-1 carrier mouse models demonstrate very little in vivo spread of infection with no evidence of disease, except for one report of tumorigenesis [125,126].”
From Current State of Therapeutics for HTLV-1 (2024) · cites this paper as [126]
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Current State of Therapeutics for HTLV-1
Wang, T. T., Hirons, A., Doerflinger, M., Morris, K. V., Ledger, S., Purcell, D. F. J., Kelleher, A. D., & Ahlenstiel, C. L. (2024) · Viruses · doi:10.3390/v16101616 · Cited by 22 · see citing works
“…mice leads to oncogenesis and other less typical manifestations of HTLV-1 infection; however, leukaemia/lymphoma induction is rare and does not fully capture the disease environment, but it has been useful to elucidate the role that tax plays in the disruption of T cell function and establish its…”
Background
- Authors
- Miwa
- Affiliations
- University of Tsukuba (JP)
- Corresponding author
- Miwa
- Venue
- International Journal of Oncology
- Publisher
- Spandidos Publications
- Published
- 2009-09-01
- Volume
- 35
- Issue
- 4
- Pages
- 701-7
- ISSN
- 1019-6439 (ISSN-L)
- 1791-2423
- OpenAlex
- W2102912756
- Cited by
- 8
- References
- 0
- Citations by year
- 2024: 1 · 2022: 1 · 2020: 1 · 2019: 1 · 2017: 1 · 2013: 2 · 2012: 1
- FWCI
- 0.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- International Journal of Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
- Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
- Keywords
- HTLV-1, adult T-cell leukemia/lymphoma, clonal expansion, proviral integration, spleen, persistent infection, tumor microenvironment, mouse model
- MeSH terms
- Animals, Animals, Newborn, Cell Line, Cell Transformation, Viral, Clone Cells, Humans, Leukemia, Myeloid, Liposarcoma, Mice, Inbred C3H, Neoplasms, Soft Tissue Neoplasms, Spleen, Splenic Neoplasms, Time Factors, Tumor Virus Infections, Human T-lymphotropic virus 1, HTLV-I Infections, Virus Integration, Viral Load, Cell Proliferation, Mice, Histiocytoma
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