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Clonality of HTLV-2 in natural infection

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: 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 May 2023 14:22
URI: https://orca.cardiff.ac.uk/id/eprint/78665

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