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La replicación del SARS-CoV-2 en el epitelio de las vías respiratorias requiere la reprogramación de los cilios

Chien-Ting Wu¹, Peter V Lidsky², Yinghong Xiao²

¹Baxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Center for Clinical Sciences Research, 269 Campus Drive, Stanford, CA, USA.

|December 29, 2022

Resumen

El virus SARS-CoV-2 utiliza cilios móviles para viajar a través del moco e infectar las células nasales. Este estudio revela cómo el virus se propaga a través de los cilios y los microvilos, afectando la transmisión del virus respiratorio.

Área de la Ciencia:

Virología
Biología celular
Medicina de las vías respiratorias

Sus antecedentes:

El mecanismo por el cual el SARS-CoV-2 infecta el epitelio nasal, superando la barrera del moco, no se entiende completamente.
Comprender las vías de entrada del virus es crucial para desarrollar contramedidas efectivas contra las infecciones respiratorias.

Objetivo del estudio:

Para aclarar el papel de las estructuras epiteliales de las vías respiratorias en la infección por SARS-CoV-2.
Para investigar el ciclo de replicación viral dentro del epitelio nasal.
Para identificar los factores del huésped que regulan la propagación del virus.

Principales métodos:

Se utilizaron cultivos organoides epiteliales nasales primarios para modelar el entorno de las vías respiratorias.
Los experimentos involucraron la observación del apego viral, la travesía y la salida usando microscopía y el agotamiento genético de los cilios.
Se emplearon fosfoproteómicos e inhibición de la quinasa para identificar las quinasas del huésped involucradas en la propagación viral.

Principales resultados:

El SARS-CoV-2 se adhiere a los cilios móviles a través del receptor ACE2 y los utiliza como huellas para penetrar en la capa de moco.
El agotamiento de los cilios inhibe significativamente la infección por SARS-CoV-2 y otros virus respiratorios.
La progenie viral utiliza microvilli para la replicación y la salida, facilitada por las quinasas activadas por p21 (PAK).
Las variantes Omicron muestran una mayor unión a los cilios móviles y una entrada viral más rápida.

Conclusiones:

Los cilios móviles y los microvilos son críticos para la replicación y propagación del SARS-CoV-2 dentro del epitelio nasal.
El transporte mucociliar juega un papel clave en la diseminación del virus a través de los tejidos de las vías respiratorias.
Las estructuras celulares del huésped y su regulación por las quinasas son objetivos importantes para las estrategias antivirales.

Palabras clave:

El COVID-19 En el caso del SARS-CoV-2 células epiteliales de las vías respiratorias Los cilios las microvillas orgánicos Las proteínas quinasas Proteomía virus de las vías respiratorias el virus respiratorio

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