HTLV-1 drives vigorous clonal expansion of infected CD8+ T cells in natural infection. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Melamed, Anat; Laydon, Daniel; Al Khatib, Hebah; Rowan, Aileen; Taylor, Graham; Bangham, Charles
• Is Part Of: Retrovirology. Volume 12:Issue 1(2015)
• Page Start: 1
• Page End: 10
• Publication Date: 2015-12
• Subjects: Human retroviral infection -- HTLV-1 -- Clonality -- Integration -- Cytotoxic T cells -- Latency; Retroviruses -- Periodicals; 579.2569
• DOI: 10.1186/s12977-015-0221-1
• Languages: English
• ISSNs: 1742-4690

Abstract

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. 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. 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.