PLoS Pathogens (Mar 2014)

Clonality of HTLV-2 in natural infection.

  • Anat Melamed,
  • Aviva D Witkover,
  • Daniel J Laydon,
  • Rachael Brown,
  • Kristin Ladell,
  • Kelly Miners,
  • Aileen G Rowan,
  • Niall Gormley,
  • David A Price,
  • Graham P Taylor,
  • Edward L Murphy,
  • Charles R M Bangham

DOI
https://doi.org/10.1371/journal.ppat.1004006
Journal volume & issue
Vol. 10, no. 3
p. e1004006

Abstract

Read online

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.