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Los gangliosidos son ligandos para los norovirus humanos
1Alberta Glycomics Centre and Department of Chemistry, University of Alberta , Edmonton, Alberta T6G 2G2, Canada.
Journal of the American Chemical Society
|August 9, 2014
Resumen
Los norovirus humanos (NoVs) se unen a los gangliosidos que contienen ácido siálico, revelando una nueva clase de factores de adhesión más allá de los antígenos del grupo sanguíneo histo (HBGAs). Este descubrimiento amplía nuestra comprensión de los mecanismos de infección por norovirus.
Área de la Ciencia:
- Virología Virología.
- Glucobiología Glucobiología.
- La bioquímica es la bioquímica.
Sus antecedentes:
- Los norovirus humanos (NoV) son una de las principales causas de la gastroenteritis viral.
- Los antígenos del grupo histo-sangre (HBGAs) son factores de adherencia establecidos para los norovirus humanos.
- El espectro completo de los receptores del huésped para los norovirus sigue siendo incompletamente entendido.
Objetivo del estudio:
- Para investigar si los glicosfingolipidos (gangliosidos) que contienen ácido siálico sirven como ligandos para los norovirus humanos.
- Para caracterizar las interacciones de unión entre las proteínas de la cápside del norovirus y los gangliosidos.
Principales métodos:
- Utilizó la espectrometría de masas de ionización por electrospray (ESI-MS) para las mediciones de unión de carbohidratos.
- Se emplearon ensayos de inmunosorbente vinculados a enzimas (ELISA) para confirmar las interacciones de unión.
- Se probaron ensamblajes de proteínas de cápside viral recombinantes (dimero P, partícula P, partícula parecida a un virus) de las cepas de NoV VA387 (GII.4) y VA115 (GI.3).
Principales resultados:
- La evidencia experimental demostró que los norovirus humanos se unen a los gangliosidos mono, di y trisializados.
- Las afinidades de unión para los gangliosidos fueron comparables en magnitud (10^210^3 M^-1) a las de los HBGAs humanos.
- Se han confirmado interacciones norovirus-ganglioside utilizando ELISA con varias construcciones de proteínas virales y glicogluados que contienen ácido siálico.
Conclusiones:
- Los gangliosidos representan una nueva clase de ligandos para los norovirus humanos.
- Estos hallazgos amplían el repertorio conocido de receptores para norovirus, impactando nuestra comprensión de la entrada viral y la patogénesis.
- El estudio proporciona una base para futuras investigaciones sobre el papel de los gangliosidos en la transmisión del norovirus y la especificidad del huésped.
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