Caracterización genómica de la integración simultánea del virus de la inmunodeficiencia humana 1 y el virus linfotrópico humano tipo1

Abstract

The selection of retroviral cDNA integration sites in the human genome is a critical step to condition the dynamics of infection. The objective was to analyze the combination of genomic characteristics of infected cells that would condition the genomic profiles of HIV-1/HTLV-1 simultaneous integration. We carried out a computer simulation using 203 human genome sequences flanking 3´LTR of both retroviruses previously deposited in the GenBank, and applying several computational tools. The analyses were focused on determining the chromosomal integration, CpG islands, Alu sequences and the expression of integration target class II genes in lymphocytic populations in a 100 kb chromatin structure associated with simultaneous integration. We found 47.3% of simultaneous cDNA integrations localized in regions rich in repetitive elements. The rest of retroviral cDNA integrations occurred in class II gene introns (p<0.05). We determined a differential chromosomal distribution for both types of provirus where HTLV-1 provirus were preferentially placed in pericentromeric and centromeric regions in contrast with HIV-1 distribution, which was registered in telomeric and subtelomeric zones (p<0.001). The genomic environment of integration for both retroviruses was characterized by genes encoding molecular binding and signal transduction, as well as by high density of CpG islands and Alu sequences. The data resulting from the computer simulation did support the hypothesis that a combination of specific chromatin characteristics would determine the dynamics of HIV-1/HTLV-1 simultaneous integration process.