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El Simian Virus 40 depende del plegamiento de la proteína ER y de los factores de control de calidad para entrar en
Mario Schelhaas1, Johan Malmström, Lucas Pelkmans
1Institute of Biochemistry, Schafmattstrasse 18, ETH Hoenggerberg, ETH Zurich, CH-8093, Zurich, Switzerland.
Cell
|November 6, 2007
Resumen
El virus Simian 40 (SV40) utiliza el retículo endoplasmático (ER) de la célula, la maquinaria de plegamiento de proteínas para desencubrir. Este proceso involucra a ERp57 y PDI, ayudando al escape viral hacia el citosol.
Área de la Ciencia:
- Virología Virología.
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
Sus antecedentes:
- El Virus Simian 40 (SV40) entra en las células a través de la endocitosis y viaja al retículo endoplasmático (ER).
- El escape viral de la ER al citosol es crucial para la infección, pero se entiende mal.
Objetivo del estudio:
- Investigar el papel de los procesos y factores asociados a ER en la infección por SV40.
- Para dilucidar los mecanismos de desencapado de SV40 y la translocación de ER.
Principales métodos:
- Análisis de la infección por SV40 en presencia de factores asociados a ER.
- Tomografía criolectrónica de las partículas SV40.
- Análisis bioquímicos para evaluar las interacciones de las proteínas y los enlaces disulfuro.
Principales resultados:
- SV40 utiliza las oxidorreductazas tiol-disulfuro de ER (ERp57, PDI) y las proteínas de retrotranslocación (Derlin-1, Sel1L).
- ERp57 isomeriza los enlaces disulfuro en la proteína cápside mayor (VP1), desacoplando las pentámeras de vértices.
- La pérdida de enlaces disulfuro y el agotamiento del calcio inducen la disociación de los pentámeros de vértices, imitando el desencubrimiento.
Conclusiones:
- SV40 secuestra la maquinaria de plegado de proteínas ER para el desmontaje inicial de la cápside.
- El virus explota las vías de degradación asociadas a ER para la translocación en el citosol.
- Este mecanismo facilita la infección SV40 al permitir el escape de la ER.
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