[Clonal expansion and genomic characterization of the human T-cell lymphotropic virus type I during the integration process in adult T-cell leukemia/lymphoma]

Abstract

Introduction: Although the integration of human T-cell lymphotropic virus type I into the T-cells is not a random process, the mechanistic details are not understood.

Objectives: The characteristics of the flanking host chromatin were evaluated at the integration sites in adult T-cell leukaemia/lymphoma (ATLL) patients infected with the virus.

Materials and methods: From seven leukemic Colombian patients positive for the human T-cell lymphotropic virus type I (HTLV-I), lymphocyte DNA samples were extracted and amplified by inverse polymerase chain reaction (IPCR). Clonal expansion and human genome nucleotide composition in an extension of 50 bp was determined. To establish the characteristics of the human genome flanking provirus, 61 IPCR sequences from Colombian and Japanese ATLL patients, were analyzed in silico to obtain insights about the genomic structure, functions and nature of associated chromatin.

Results: The clonal expansion of cell clones was predominantly oligoclonal. From 61 IPCR sequences, 155 alignments with homology higher than 95% (e-value < 0.05) were screened. Seventy-five percent of those sequences corresponded to non coding elements that include repetitive and non-repetitive DNA. Fifty percent of the proviral integrations were associated with chromosomes of A and B groups. Viral DNA integration tended to favor exons of genes that replicated early, controlled the cell cycle, or were involved in signal transduction.

Conclusions: The results indicated that HTLV-I integration was preferentially directed towards genomic environments with high C:G content, and toward genes that replicate early, regulate cell cycle or involved with signal transduction.