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Las señales de kinasa Abl y Fyn inducidas por el virus permiten la entrada del coxsackievirus a través de las uniones
Carolyn B Coyne1, Jeffrey M Bergelson
1Division of Infectious Diseases, The Children's Hospital of Philadelphia, University of Pennsylvania, PA 19104, USA.
Cell
|January 18, 2006
Resumen
Los coxsackievirus del grupo B (CVB) utilizan el factor de aceleración de la descomposición (DAF) para activar las vías de señalización. Esto permite que el virus se mueva a uniones estrechas y cruce la barrera epitelial para la infección.
Área de la Ciencia:
- Virología Virología.
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
Sus antecedentes:
- Los coxsackievirus del grupo B (CVB) deben romper la barrera epitelial para iniciar la infección.
- El coxsackievirus y el receptor del adenovirus (CAR), ubicado en uniones estrechas, no son accesibles desde la superficie apical.
- Los CVB con frecuencia interactúan con el factor de aceleración de la descomposición (DAF), una proteína anclada en el GPI.
Objetivo del estudio:
- Para aclarar el mecanismo por el cual los CVBs atraviesan la barrera epitelial.
- Para investigar los roles de DAF y CAR en la infección por CVB.
- Para identificar las vías de señalización explotadas por los CVB para la entrada de células epiteliales.
Principales métodos:
- Se investigaron las interacciones entre virus y huésped utilizando modelos de cultivo celular.
- Utilizó inhibidores de la quinasa y la manipulación genética para sondear las vías de señalización.
- Se examinó la entrada del virus y los mecanismos de transporte intracelular.
Principales resultados:
- La unión apical a DAF activa la Abl quinasa, induciendo reorganizaciones de actina dependientes de Rac para la translocación del virus a uniones estrechas.
- En las uniones estrechas, la interacción CAR induce cambios conformacionales en la cápside esenciales para la entrada viral y la liberación de ARN.
- El compromiso de DAF también activa la quinasa Fyn, lo que lleva a la fosforilación de la caveolina y a la captación viral mediada por las caveolas.
Conclusiones:
- Los CVB utilizan la señalización mediada por DAF para superar las barreras epiteliales.
- El virus secuestra la maquinaria de la célula huésped, que involucra a las quinasas Abl y Fyn, la remodelación de la actina y las cuevas, para una entrada eficiente.
- Comprender estos mecanismos proporciona información sobre la patogénesis viral y las posibles dianas terapéuticas.
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