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El factor de transcripción TFIIH, un objetivo para el virus de la fiebre hemorrágica del Valle del Rift
Nicolas Le May1, Sandy Dubaele, Luca Proietti De Santis
1Unité de Génétique Moléculaire des Bunyaviridés, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris, Cedex 15, France.
Cell
|February 26, 2004
Resumen
El virus de la fiebre del Valle del Rift (RVFV) suprime la síntesis de ARN del huésped al atacar el factor de transcripción TFIIH. La proteína NSs viral interrumpe el ensamblaje de TFIIH, lo que lleva a la desestabilización de la célula huésped y la evasión inmune.
Área de la Ciencia:
- Virología Virología.
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
Sus antecedentes:
- El virus de la fiebre del Valle del Rift (RVFV) causa enfermedades graves en humanos y animales.
- La infección por RVFV inhibe severamente la síntesis de ARN celular del huésped.
Objetivo del estudio:
- Para dilucidar el mecanismo molecular por el cual RVFV suprime la síntesis de ARN del huésped.
- Para identificar la proteína viral responsable de interrumpir la transcripción del huésped.
Principales métodos:
- La levadura tiene un sistema de dos híbridos.
- Expresión y purificación de proteínas recombinantes.
- La microscopía confocal es una microscopía confocal.
Principales resultados:
- La infección por RVFV reduce la concentración del factor de transcripción TFIIH.
- La proteína viral no estructural NSs interactúa con las subunidades TFIIH p44 y XPB.
- La proteína NSs forma filamentos nucleares, secuestrando los componentes del TFIIH y evitando su ensamblaje.
- Esta interrupción compite con el enlace de XPD, desestabilizando la función TFIIH.
Conclusiones:
- RVFV utiliza la proteína NSs para interrumpir la transcripción del huésped al interferir con el ensamblaje de TFIIH.
- Este mecanismo es crucial para la capacidad de RVFV para evadir las respuestas inmunes del huésped.
- Dirigirse al TFIIH es una estrategia viral clave para la replicación y la patogénesis.
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