Clonality of HTLV-2 in Natural Infection

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. © 2014 melamed et al.