Characterization of HTLV-1 Infectious Molecular Clone Isolated from Patient with HAM/TSP and Immortalization of Human Primary T-Cell Lines
Human T-cell leukemia virus (HTLV-1) is the etiological agent of lymphoproliferative diseases such as adult T-cell leukemia and T-cell lymphoma (ATL) and a neurodegenerative disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). While several molecular clones of HTLV-1...
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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-11-01
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| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/16/11/1755 |
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| Summary: | Human T-cell leukemia virus (HTLV-1) is the etiological agent of lymphoproliferative diseases such as adult T-cell leukemia and T-cell lymphoma (ATL) and a neurodegenerative disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). While several molecular clones of HTLV-1 have been published, all were isolated from samples derived from patients with adult T-cell leukemia. Here, we report the characterization of an HTLV-1 infectious molecular clone isolated from a sample of a patient with HAM/TSP disease. Genetic comparative analyses of the HAM/TSP molecular clone (pBST) revealed unique genetic alterations and specific viral mRNA expression patterns. Interestingly, our clone also harbors characteristics previously published to favor the development of HAM/TSP disease. The molecular clone is capable of infection and immortalization of human primary T cells in vitro. Our studies further demonstrate that the HTLV-1 virus produced from primary T cells transfected with pBST or ACH molecular clones cannot sustain long-term expansion, and cells cease to proliferate after 3–4 months in culture. In contrast, long-term proliferation and immortalization were achieved if the virus was transmitted from dendritic cells to primary T cells, and secondary infection of 729B cells in vitro was demonstrated. In both primary T cells and 729B cells, pBST and ACH were latent, and only <i>hbz</i> viral RNA was detected. This study suggests that HTLV-1 transmission from DC to T cells favors the immortalization of latently infected cells. |
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| ISSN: | 1999-4915 |