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Los provirus no inducidos competentes para la replicación en el reservorio latente aumentan la barrera para curar el
Ya-Chi Ho1, Liang Shan, Nina N Hosmane
1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Cell
|November 19, 2013
Resumen
Los provirus latentes del VIH-1 persisten en las células T CD4 (((+) en reposo, lo que dificulta las curas. Se descubrió que los provirus intactos y no inducidos eran capaces de replicarse, lo que aumentaba significativamente el tamaño estimado del depósito latente.
Área de la Ciencia:
- Virología Virología.
- Inmunología Inmunología.
- Biología Molecular Biología Molecular
Sus antecedentes:
- La terapia antirretroviral (TAR) no puede curar la infección por el VIH-1 debido a los persistentes provirus latentes en las células T CD4 ((+) en reposo.
- La activación de las células T induce a <1% de los provirus latentes a liberar el virus infeccioso, y los provirus no inducidos a menudo se presumen defectuosos.
Objetivo del estudio:
- Caracterizar la naturaleza y la capacidad de replicación de los provirus latentes no inducidos del VIH-1.
- Reevaluar el tamaño del reservorio latente del VIH-1 y sus implicaciones para lograr una cura.
Principales métodos:
- Análisis de 213 clones provirales no inducidos de pacientes tratados con VIH-1.
- Secuenciación directa y síntesis del genoma para reconstruir clones provirales intactos de longitud completa.
- Evaluación de la función de repetición terminal larga (LTR) y cinética de crecimiento viral.
Principales resultados:
- El 11,7% de los clones provirales no inducidos poseían genomas intactos con función LTR normal, en contraste con el 88,3% que contenía defectos.
- Los provirus no inducidos intactos reconstruidos exhibieron una cinética de crecimiento comparable a los provirus inducidos.
- Se encontraron provirus no inducidos integrados en unidades de transcripción activas con promotores no metilados.
Conclusiones:
- Existen provirus no inducidos del VIH-1 capaces de replicarse dentro del reservorio latente.
- El reservorio latente del VIH-1 puede ser significativamente mayor de lo estimado anteriormente, potencialmente hasta 60 veces mayor.
- La presencia de estos provirus intactos plantea una barrera sustancial para la curación del VIH-1.
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