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El pico de SARS-CoV-2 D614G mejora la replicación y la transmisión
Bin Zhou1, Tran Thi Nhu Thao2,3,4, Donata Hoffmann5
1CDC COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Nature
|February 26, 2021
Resumen
La mutación D614G en la proteína del pico del SARS-CoV-2 mejora la unión y la replicación del virus. Esta variante muestra una mayor transmisibilidad en modelos animales, lo que explica su dominio global.
Área de la Ciencia:
- Virología
- Biología molecular
- Epidemiología
Sus antecedentes:
- La sustitución de D614G en la glicoproteína de pico (S) del SARS-CoV-2 se ha vuelto predominante a nivel mundial.
- Las razones de la prevalencia de esta variante, ya sea la ventaja de la aptitud o los efectos del fundador, no estaban claras.
Objetivo del estudio:
- Investigar el impacto funcional de la sustitución D614G en la replicación y transmisión del SARS-CoV-2.
- Para determinar si la variante D614G posee una ventaja de aptitud.
Principales métodos:
- Se utilizaron variantes isogénicas del SARS-CoV-2 que solo difieren en la sustitución D614G.
- Se ha evaluado la unión viral a los receptores de la enzima convertidora de angiotensina 2 (ACE2) en humanos.
- Replicación medida en cultivos epiteliales de las vías respiratorias humanas y en ratones noqueadores ACE2.
- Se ha evaluado la replicación y la transmisibilidad en modelos de hámster y hurón.
Principales resultados:
- La variante D614G demostró una mayor unión a la ACE2 humana.
- Se observó un aumento de la replicación viral en células de las vías respiratorias humanas y en modelos in vivo.
- Se observó una replicación y transmisión notablemente más altas en modelos de hámster y hurón.
- La sustitución de D614G confería una ventaja competitiva, especialmente durante los cuellos de botella de la transmisión.
Conclusiones:
- La sustitución de D614G en la proteína del pico del SARS-CoV-2 proporciona una ventaja significativa de aptitud in vivo.
- La unión y la replicación mejoradas contribuyen a la mayor transmisibilidad de la variante.
- Este estudio explica el predominio global de la variante D614G del SARS-CoV-2.
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