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El camino evolutivo hacia la virulencia de un virus de ARN
Adi Stern1, Ming Te Yeh2, Tal Zinger1
1Department of Molecular Microbiology and Biotechnology, Tel-Aviv University, Tel-Aviv 6997801, Israel.
Cell
|March 25, 2017
Resumen
Las cepas de la vacuna oral contra la poliomielitis (OPV) pueden recuperar su virulencia, causando epidemias. Este estudio revela caminos evolutivos comunes y eventos moleculares que impulsan el resurgimiento del poliovirus, ayudando al desarrollo de vacunas más seguras.
Área de la Ciencia:
- Virología
- Biología evolutiva
- Vacunas y vacunas
Sus antecedentes:
- Históricamente, la poliomielitis paralítica afectaba a millones de niños cada año.
- La vacuna oral contra la poliomielitis (OPV) redujo significativamente la incidencia de la enfermedad en todo el mundo.
- Las epidemias de poliovirus derivadas de las vacunas obstaculizan actualmente los esfuerzos mundiales de erradicación.
Objetivo del estudio:
- Aclarar los mecanismos moleculares y las trayectorias evolutivas de las cepas de OPV que se vuelven virulentas.
- Identificar eventos evolutivos comunes en las epidemias de poliovirus derivadas de la vacuna.
- Desarrollar un marco para diseñar cepas de vacunas más seguras y predecir la virulencia viral.
Principales métodos:
- Combinó el modelado teórico y la evolución experimental en un sistema basado en células.
- Experimentos de evolución acelerada para replicar las mutaciones que provocan epidemias.
- Evaluación de la capacidad de replicación viral en cultivos celulares y de la virulencia en un modelo animal.
Principales resultados:
- Se identificaron eventos evolutivos conservados y vías de mutación en la mayoría de las epidemias de poliovirus derivadas de la vacuna.
- Se demostró que las mutaciones acumuladas mejoran la capacidad de replicación viral.
- Se demostró un aumento de la virulencia en un modelo animal correlacionado con las mutaciones observadas.
Conclusiones:
- Las cepas de poliovirus derivadas de la vacuna pueden evolucionar a formas patógenas a través de estrategias evolutivas específicas, a menudo similares.
- Los hallazgos proporcionan información sobre la base molecular de la virulencia del poliovirus.
- Esta investigación ofrece una base para desarrollar vacunas mejoradas y más seguras contra la poliomielitis y pronosticar la patogenicidad viral.
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