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Varios orígenes de la persistencia del virus durante el control natural de la infección por VIH
Eli A Boritz1, Samuel Darko1, Luke Swaszek1
1Human Immunology Section, Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
Cell
|July 26, 2016
Resumen
Comprender la persistencia del VIH es clave para desarrollar una cura. Este estudio revela tres mecanismos, incluida la replicación activa en los ganglios linfáticos y la expansión clonal de las células infectadas, que mantienen el virus de la inmunodeficiencia humana (VIH) en los controladores.
Área de la Ciencia:
- Virología
- Inmunología
- La genética
Sus antecedentes:
- Las estrategias de curación dirigidas al virus de la inmunodeficiencia humana (VIH) requieren una comprensión completa de los mecanismos de persistencia viral.
- Las personas con control virológico natural ofrecen un modelo único para estudiar cómo se mantiene el VIH a pesar de las respuestas inmunes efectivas.
Objetivo del estudio:
- Esclarecer los mecanismos de replicación del VIH y la persistencia de las células T CD4 en individuos con control natural del VIH.
- Identificar los compartimentos anatómicos y funcionales donde se mantienen los depósitos de VIH.
Principales métodos:
- Secuenciación de genomas virales, genes de receptores de células T y sitios de integración del VIH.
- Análisis de transcriptomas celulares de las células T CD4 infectadas.
- Seguimiento de la replicación del VIH y la persistencia de las células infectadas en los tejidos linfoides y la sangre.
Principales resultados:
- Se identificaron tres mecanismos distintos de persistencia del VIH en diferentes compartimentos del cuerpo.
- Se detectó la replicación activa del VIH en las células de memoria del folículo T (TFH) y no-TFH dentro de los ganglios linfáticos.
- Se encontraron provirus inducibles de origen archivado y reciente en células en circulación y altamente diferenciadas, expandidas clonalmente en la sangre.
Conclusiones:
- La persistencia del VIH en los controladores es un proceso multifacético que implica la replicación activa en los tejidos linfoides, la expansión clonal de las células infectadas y la recirculación de las células recientemente infectadas.
- Estos mecanismos combinados contribuyen a mantener el reservorio viral a pesar de la sólida inmunidad antiviral.
- La definición de estas vías de persistencia es crucial para diseñar intervenciones efectivas de curación del VIH.
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