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El complejo de prefoldina promueve la expresión génica estimulada por el interferón y es inhibido por el rotavirus
Yinxing Zhu1, Yanhua Song2,3, Dilip Kumar4,5
1Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
Nature communications
|August 29, 2025
Resumen
La proteína VP3 del rotavirus interrumpe la defensa antiviral del huésped al inhibir el complejo prefoldina-UBA3, que es crucial para la expresión del gen estimulado por el interferón (ISG). Esta interacción debilita la respuesta inmune contra las infecciones virales.
Área de la Ciencia:
- Virología
- Inmunología
- Biología molecular
Sus antecedentes:
- El interferón (IFN) y los genes estimulados por el interferón (ISG) son vitales para la defensa del huésped contra los virus.
- Se sabe que la proteína VP3 del rotavirus antagoniza la respuesta al interferón, pero su mecanismo no está claro.
Objetivo del estudio:
- Para aclarar el mecanismo molecular por el cual el rotavirus VP3 antagoniza la inmunidad antiviral del huésped.
- Para identificar las proteínas celulares que interactúan con el rotavirus VP3.
Principales métodos:
- Purificación de afinidad en tándem junto con espectrometría de masas de alta resolución para identificar socios de unión VP3.
- Cuantificación libre de etiquetas en todo el proteoma para analizar cambios en la expresión de proteínas.
- Análisis de la infección por rotavirus en las células knockout de la subunidad de prefoldina.
Principales resultados:
- El complejo de prefoldina fue identificado como un socio clave de unión celular del rotavirus VP3.
- El nocaut de las subunidades de prefoldina aumentó significativamente la infección por rotavirus.
- Prefoldin facilita el plegamiento de UBA3 (enzima 3 activadora de modificadores similares a la ubiquitina), que regula positivamente la expresión de ISG.
- El rotavirus VP3 se une directamente a la prefoldina, inhibiendo su actividad de chaperona, lo que lleva a la inestabilidad de UBA3, a la reducción de IRF9 y a la supresión de la transcripción de ISG.
Conclusiones:
- Se ha informado de un nuevo eje prefoldina-UBA3-IRF9-ISG crítico para la inmunidad antiviral.
- El rotavirus VP3 antagoniza la inmunidad del huésped al interrumpir este eje.
- Estos hallazgos ofrecen objetivos potenciales para el desarrollo terapéutico antiviral de amplio espectro.
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