In this work, we demonstrate that the extent of HTLV-2-infected cell expansion significantly exceeds that of HTLV-1-infected cells in healthy carriers, approximating instead to that observed in patients with HTLV-1-associated leukemia. It is well established that HTLV-1-infected cells undergo clonal expansion in infected individuals, but little is known about clonality in HTLV-2 infection. HTLV-2 has not been linked with a specific disease, whereas HTLV-1 infection can cause leukemia and profound neuropathology. They differ in their preferred host T-cell type and in their possible clinical outcomes. The two human retroviruses HTLV-1 and HTLV-2 are similar in their structure, replication cycle and the manner through which they spread between and within individuals. In addition, our data demonstrate that strong virus-driven proliferation per se does not predispose to malignant transformation in oncoretroviral infections. 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. The HTLV-2 load correlated significantly with the degree of dispersion of the clone frequency distribution, which was highly stable over ∼8 years. 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. 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. 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. However, T-cell clonality in HTLV-2 infection has not been rigorously characterized. Virus-driven clonal proliferation of infected cells both in vitro and in vivo has been demonstrated in HTLV-1 infection. 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.
Human T-lymphotropic virus type 1 (HTLV-1) and type 2 (HTLV-2) both cause lifelong persistent infections, but differ in their clinical outcomes.
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