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La mutación de punta D614G altera la aptitud para el SARS-CoV-2

Jessica A Plante^1,2,3, Yang Liu⁴, Jianying Liu^2,3

¹World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA.

|October 27, 2020

Resumen

La mutación de la proteína del pico D614G del SARS-CoV-2 mejora la replicación y la propagación del virus. Es poco probable que esta variante reduzca significativamente la eficacia de la vacuna contra el COVID-19, pero los anticuerpos terapéuticos requieren pruebas.

Área de la Ciencia:

Virología
Enfermedades infecciosas
Vacunas y vacunas

Sus antecedentes:

La sustitución D614G en la proteína del pico del SARS-CoV-2 se convirtió en la variante dominante durante la pandemia de COVID-19.
El impacto preciso de la variante D614G en la transmisión viral y la eficacia de las vacunas existentes no estaba claro.

Objetivo del estudio:

Para investigar los efectos funcionales de la mutación de la proteína del pico D614G del SARS-CoV-2.
Evaluar las implicaciones de la variante D614G para la propagación viral, la infectividad y la inmunidad inducida por la vacuna.

Principales métodos:

Diseñó la sustitución de la proteína del pico D614G en la cepa del SARS-CoV-2 USA-WA1/2020.
Se ha evaluado la replicación viral en células epiteliales del pulmón humano y en tejidos primarios de las vías respiratorias humanas.
Hamsters infectados con virus de tipo salvaje (D614) y mutantes (G614) y carga viral medida.
Actividad de neutralización evaluada de sueros de hámster contra los virus D614 y G614.

Principales resultados:

La sustitución de D614G aumentó la replicación viral en las células pulmonares humanas y en los tejidos de las vías respiratorias al aumentar la infectividad y la estabilidad de los viriones.
El virus G614 produjo títulos infecciosos más altos en las vías respiratorias superiores (lavado nasal, tráquea) de los hámsters infectados, pero no en los pulmones.
El suero de hámsters infectados por D614 mostró títulos de neutralización modestamente más altos contra G614 en comparación con el virus D614.

Conclusiones:

La mutación D614G contribuye significativamente al aumento de la carga viral en el tracto respiratorio superior, apoyando una mayor transmisión del SARS-CoV-2.
Es poco probable que la variante D614G disminuya sustancialmente la eficacia protectora de las vacunas desarrolladas contra cepas anteriores de SARS-CoV-2.
Los anticuerpos terapéuticos deben evaluarse contra la variante G614 que circula actualmente para garantizar la efectividad en el tratamiento de COVID-19.

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