El gen de la enfermedad humana LYSET es esencial para el transporte de enzimas lisosomales y la infección viral
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Updated: Aug 29, 2025
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Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus
Published on: October 7, 2011
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Christopher M Richards1, Sabrina Jabs2, Wenjie Qiao1
1Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Science (New York, N.Y.)
|September 8, 2022
Resumen
El factor de tráfico de enzimas lisosomales (LYSET) es crucial para la clasificación de proteínas celulares y las infecciones virales. La deficiencia de LYSET causa trastornos de almacenamiento lisosómico y empeora la infección por SARS-CoV-2.
Área de la Ciencia:
- Biología celular
- Biología molecular
- Virología
Sus antecedentes:
- Los lisosomas son orgánulos celulares vitales para la degradación.
- El etiquetado de 6-fosfato de manosa (M6P) dirige las enzimas a los lisosomas a través de la GlcNAc-1-fosfotransferasa.
- La deficiencia en esta vía causa mucolipidosis II (MLII), un trastorno de almacenamiento lisosomal severo.
- Los virus dependientes de la catepsina, incluido el SARS-CoV-2, dependen de los lisosomas funcionales.
Objetivo del estudio:
- Identificar nuevos factores involucrados en el tráfico de enzimas lisosomales.
- Investigar el papel de LYSET en el etiquetado M6P y la infección viral.
- Para aclarar la base molecular de los trastornos asociados con LYSET.
Principales métodos:
- Se emplearon pantallas CRISPR a escala genómica para identificar los genes esenciales.
- La función de LYSET se evaluó en células knockout y ratones.
- Los ensayos de infección viral se realizaron utilizando virus dependientes de la catepsina.
- Se realizaron estudios bioquímicos y de localización celular.
Principales resultados:
- Las pantallas CRISPR a escala genómica identificaron a LYSET (TMEM251) como esencial para las infecciones virales dependientes de la catepsina, incluido el SARS-CoV-2.
- La deficiencia de LYSET condujo a una pérdida global de etiquetado M6P y a una mala localización de la GlcNAc-1-fosfosferasa.
- Los ratones eliminados de Lyset mostraron fenotipos similares a los de MLII.
- Las mutaciones LYSET humanas patógenas no pudieron rescatar los defectos de clasificación lisosómica.
Conclusiones:
- LYSET es indispensable para el buen funcionamiento de la maquinaria de tráfico lisosomal M6P.
- Las mutaciones LYSET son causantes de un trastorno parecido al MLII.
- LYSET es un factor huésped crítico para los virus dependientes de las catepsinas lisosomales.
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