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El factor de coagulación X activa la inmunidad innata al adenovirus de la especie humana C
Konstantin Doronin1, Justin W Flatt, Nelson C Di Paolo
1Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Science (New York, N.Y.)
|September 29, 2012
Resumen
El adenovirus humano utiliza el factor de coagulación X (FX) para desencadenar la inmunidad innata a través de la señalización del receptor tipo Toll 4 (TLR4). El bloqueo de esta interacción previene la activación del gen inmune, revelando un nuevo mecanismo inmunológico virus-hospedador.
Área de la Ciencia:
- Inmunología Inmunología.
- Virología Virología.
- Biología de la coagulación Biología de la coagulación.
Sus antecedentes:
- El papel de los factores de coagulación en la mayor inmunidad del organismo no está claro.
- Los cangrejos herradura utilizan la coagulación para la defensa, pero esto se entiende mal en los seres humanos.
Objetivo del estudio:
- Investigar el papel del factor de coagulación X (FX) en la activación inmune innata del adenovirus humano de la especie C (HAdv).
- Para dilucidar la vía de señalización desencadenada por el complejo HAdv-FX.
Principales métodos:
- Modelado de la interfaz de interacción HAdv-FX.
- Introducir mutaciones para anular la formación del complejo HAdv-FX.
- Realización de perfiles de transcripción de todo el genoma in vivo.
Principales resultados:
- El complejo HAdv-FX activa una red específica de genes de respuesta temprana dependientes del factor nuclear κB (NF-κB).
- El HAdv ablado de unión a FX no logró activar estos genes inmunes.
- Esta activación ocurre aguas abajo de la señalización del receptor tipo Toll 4 (TLR4) / MyD88/TRIF/TRAF6.
Conclusiones:
- La "decoración" del factor huésped de los virus es un mecanismo para activar los sensores inmunes innatos.
- El estudio identifica una nueva respuesta inmune innata a la entrada viral que involucra la coagulación mal localizada FX.
- Este mecanismo pone de relieve la interacción entre la coagulación y la inmunidad innata en la defensa antiviral.
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