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06:03
Use of Viral Entry Assays and Molecular Docking Analysis for the Identification of Antiviral Candidates against Coxsackievirus A16
Published on: July 15, 2019
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PLA2G16 representa un cambio entre la entrada y la salida de Picornaviridae
Jacqueline Staring1, Eleonore von Castelmur1, Vincent A Blomen1
1Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Nature
|January 13, 2017
Resumen
Los investigadores descubrieron que la enzima PLA2G16 es crucial para que los picornavirus entreguen su genoma a las células huésped. Este hallazgo revela un nuevo paso en la infección viral en el que el virus debe superar un mecanismo de defensa celular para replicarse.
Área de la Ciencia:
- Virología
- Biología celular
- Interacciones huésped-patógeno
Sus antecedentes:
- Los picornavirus causan enfermedades humanas y animales significativas.
- Si bien se conoce la unión al receptor, el mecanismo de entrega del genoma citoplasmático sigue sin estar claro.
- Los factores de acogida que facilitan este proceso son en gran medida no identificados.
Objetivo del estudio:
- Identificar los factores del huésped esenciales para la transmisión del genoma del picornavirus al citoplasma.
- Aclarar el papel específico de los factores huésped identificados en el ciclo de vida viral.
- Comprender la interacción entre los mecanismos de entrada del virus y las vías de defensa celular del huésped.
Principales métodos:
- Se emplearon pantallas genéticas haploides de todo el genoma para identificar los factores del huésped.
- Se realizaron ensayos funcionales para determinar el papel de PLA2G16 en la infección viral.
- Se realizaron exámenes de supresor para identificar los mecanismos celulares que lo contrarrestan.
Principales resultados:
- La enzima modificadora de lípidos fosfolipasa A2 del grupo 16 (PLA2G16) fue identificada como un factor huésped crítico del picornavirus.
- PLA2G16 se requiere para la entrega del genoma mediada por viriones en el citoplasma, un evento distinto de la unión celular o el tráfico endosómico.
- Se encontró que Galectin-8, un sensor de endosomas permeados, media el aclaramiento, mientras que PLA2G16 facilita la translocación del genoma y previene este aclaramiento.
Conclusiones:
- PLA2G16 juega un papel vital en la liberación del genoma del picornavirus en el citoplasma de la célula huésped.
- La entrada viral desencadena vías competidoras: un mecanismo de eliminación activado por poros y el reclutamiento de PLA2G16 para la entrega del genoma.
- Este estudio revela un nuevo mecanismo de translocación del genoma viral y la interacción huésped-patógeno durante la infección por picornavirus.
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