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Clonality of HTLV-2 in natural infection

Melamed, Anat, Witkover, Aviva D., Laydon, Daniel J., Brown, Rachael, Ladell, Kristin, Miners, Kelly, Rowan, Aileen G., Gormley, Niall, Price, David, 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: Medicine
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: 06 Feb 2019 17:24
URI: http://orca.cf.ac.uk/id/eprint/78665

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