Melamed, Anat, Witkover, Aviva D., Laydon, Daniel J., Brown, Rachael, Ladell, Kristin  ORCID: https://orcid.org/0000-0002-9856-2938, Miners, Kelly, Rowan, Aileen G., Gormley, Niall, Price, David ORCID: https://orcid.org/0000-0001-9416-2737, Taylor, Graham P., Murphy, Edward L. and Bangham, Charles R. M.
2014.
Clonality of HTLV-2 in natural infection.
PLoS Pathogens
10
(3)
, e1004006.
10.1371/journal.ppat.1004006
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Abstract
Human T-lymphotropic virus type 1 (HTLV-1) and type 2 (HTLV-2) both cause lifelong persistent infections, but differ in their clinical outcomes. HTLV-1 infection causes a chronic or acute T-lymphocytic malignancy in up to 5% of infected individuals whereas HTLV-2 has not been unequivocally linked to a T-cell malignancy. Virus-driven clonal proliferation of infected cells both in vitro and in vivo has been demonstrated in HTLV-1 infection. However, T-cell clonality in HTLV-2 infection has not been rigorously characterized. In this study we used a high-throughput approach in conjunction with flow cytometric sorting to identify and quantify HTLV-2-infected T-cell clones in 28 individuals with natural infection. We show that while genome-wide integration site preferences in vivo were similar to those found in HTLV-1 infection, expansion of HTLV-2-infected clones did not demonstrate the same significant association with the genomic environment of the integrated provirus. The proviral load in HTLV-2 is almost confined to CD8+ T-cells and is composed of a small number of often highly expanded clones. The HTLV-2 load correlated significantly with the degree of dispersion of the clone frequency distribution, which was highly stable over ~8 years. These results suggest that there are significant differences in the selection forces that control the clonal expansion of virus-infected cells in HTLV-1 and HTLV-2 infection. In addition, our data demonstrate that strong virus-driven proliferation per se does not predispose to malignant transformation in oncoretroviral infections.
| Item Type: | Article |
|---|---|
| Date Type: | Published Online |
| Status: | Published |
| Schools: | Schools > Medicine Research Institutes & Centres > Systems Immunity Research Institute (SIURI) |
| Subjects: | Q Science > QR Microbiology > QR355 Virology |
| Publisher: | Public Library of Science |
| ISSN: | 1553-7374 |
| Date of First Compliant Deposit: | 6 September 2017 |
| Date of Acceptance: | 2 February 2014 |
| Last Modified: | 16 Dec 2023 15:43 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/78665 |
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