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PLoS Pathog. 2014 Mar 13;10(3):e1004006. doi: 10.1371/journal.ppat.1004006. eCollection 2014.

Clonality of HTLV-2 in natural infection.

Author information

  • 1Section of Immunology, Imperial College London, Wright-Fleming Institute, London, United Kingdom.
  • 2Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom.
  • 3Illumina, Little Chesterford, Essex, United Kingdom.
  • 4Section of Infectious Diseases, Imperial College London, Wright-Fleming Institute, London, United Kingdom.
  • 5Departments of Laboratory Medicine and Epidemiology/Biostatistics, University of California San Francisco and Blood Systems Research Institute, San Francisco, California, United States of America.

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.

PMID:
24626195
[PubMed - indexed for MEDLINE]
PMCID:
PMC3953477
Free PMC Article
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