DOI: http://dx.doi.org/10.18257/raccefyn.183

Artículo de revisión

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

Martha C. Domínguez, Lina Andrea Alzate, Felipe Garcia - Vallejo

Resumen


La selección de los sitios de integración del ADN retroviral en el genoma es crucial para moldear la dinámica de la infección. El objetivo de este estudio fue analizar la combinación específica de las características genómicas de la célula infectada que condicionarían la integración simultánea de ambos retrovirus. A partir de 203 secuencias de ADN humano vecinas a las repeticiones terminales largas (long terminal repeat, LTR) de ambos virus, depositadas en el GenBank, y mediante distintas herramientas computacionales, se hizo una simulación bioinformática para determinar la integración del VIH y el -HTLV-1 en una extensión de 100 kb, así como la localización cromosómica del provirus, el número de genes, su proceso molecular y función asociada, las islas CpG, las secuencias Alu y los elementos nucleares dispersos largos (long interspersed nuclear element, LINE), y su expresión en poblaciones de linfocitos de los genes blanco de la integración. El 47,3 % de las integraciones de ambos virus se localizó en regiones ricas en elementos repetidos. La integración en los genes de la clase II ocurrió en los intrones (p<0,05). Se observó una distribución cromosómica diferencial de ambos provirus en la que el HTLV-1 se localizó en regiones pericentroméricas y centroméricas, mientras que el VIH-1 lo hizo en zonas teloméricas y subteloméricas (p<0,001).
El ambiente común para la integración de los linfocitos en el genoma estuvo conformado por genes codificantes de proteínas de unión a moléculas y de transducción de señales, así como por un elevado número de islas CpG y de repeticiones Alu. A partir de la simulación bioinformática de la integración entre el VIH-1 y el HTLV-1, se aportó evidencia que sustenta la hipótesis de que una combinación específica de variables genómicas condicionaría el proceso de integración diferencial simultánea de ambos retrovirus. Palabras clave: retrovirus, integración viral, linfocitos, islas de CpG, genes clase II, simulación por computador.


Palabras clave


retrovirus; cointegración retroviral; linfocitos, isla CpG; genes clase II; simulación computacional

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