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HTLV-1 drives vigorous clonal expansion of infected CD8(+) T cells in natural infection.
- Source :
-
Retrovirology [Retrovirology] 2015 Nov 09; Vol. 12, pp. 91. Date of Electronic Publication: 2015 Nov 09. - Publication Year :
- 2015
-
Abstract
- Background: Human T-lymphotropic Virus Type I (HTLV-1) is a retrovirus that persistently infects 5-10 million individuals worldwide and causes disabling or fatal inflammatory and malignant diseases. The majority of the HTLV-1 proviral load is found in CD4(+) T cells, and the phenotype of adult T cell leukemia (ATL) is typically CD4(+). HTLV-1 also infects CD8(+) cells in vivo, but the relative abundance and clonal composition of the two infected subpopulations have not been studied. We used a high-throughput DNA sequencing protocol to map and quantify HTLV-1 proviral integration sites in separated populations of CD4(+) cells, CD8(+) cells and unsorted peripheral blood mononuclear cells from 12 HTLV-1-infected individuals.<br />Results: We show that the infected CD8(+) cells constitute a median of 5% of the HTLV-1 proviral load. However, HTLV-1-infected CD8(+) clones undergo much greater oligoclonal proliferation than the infected CD4(+) clones in infected individuals, regardless of disease manifestation. The CD8(+) clones are over-represented among the most abundant clones in the blood and are redetected even after several years.<br />Conclusions: We conclude that although they make up only 5% of the proviral load, the HTLV-1-infected CD8(+) T-cells make a major impact on the clonal composition of HTLV-1-infected cells in the blood. The greater degree of oligoclonal expansion observed in the infected CD8(+) T cells, contrasts with the CD4(+) phenotype of ATL; cases of CD8(+) adult T-cell leukaemia/lymphoma are rare. This work is consistent with growing evidence that oligoclonal expansion of HTLV-1-infected cells is not sufficient for malignant transformation.
- Subjects :
- Adult
CD4-Positive T-Lymphocytes virology
CD8-Positive T-Lymphocytes physiology
Clone Cells
High-Throughput Nucleotide Sequencing
Humans
Leukocytes, Mononuclear
Middle Aged
Proviruses
T-Lymphocytes, Cytotoxic immunology
Viral Load
Virus Integration
Virus Latency
CD8-Positive T-Lymphocytes virology
HTLV-I Infections immunology
HTLV-I Infections virology
Human T-lymphotropic virus 1 immunology
Human T-lymphotropic virus 1 physiology
T-Lymphocytes, Cytotoxic virology
Subjects
Details
- Language :
- English
- ISSN :
- 1742-4690
- Volume :
- 12
- Database :
- MEDLINE
- Journal :
- Retrovirology
- Publication Type :
- Academic Journal
- Accession number :
- 26552867
- Full Text :
- https://doi.org/10.1186/s12977-015-0221-1