Coronavirus hemagglutinin-esterase and spike proteins coevolve for functional balance and optimal virion avidity.
Proc Natl Acad Sci U S A
; 117(41): 25759-25770, 2020 10 13.
Artículo
en Inglés
| MEDLINE | ID: covidwho-807358
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Este artículo de revista científica es probablemente basado en un preprint previamente disponible, por medio del reconocimiento de similitud realizado por una máquina. La confirmación humana aún está pendiente.
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Este artículo de revista científica es probablemente basado en un preprint previamente disponible, por medio del reconocimiento de similitud realizado por una máquina. La confirmación humana aún está pendiente.
Ver preprint
ABSTRACT
Human coronaviruses OC43 and HKU1 are respiratory pathogens of zoonotic origin that have gained worldwide distribution. OC43 apparently emerged from a bovine coronavirus (BCoV) spillover. All three viruses attach to 9-O-acetylated sialoglycans via spike protein S with hemagglutinin-esterase (HE) acting as a receptor-destroying enzyme. In BCoV, an HE lectin domain promotes esterase activity toward clustered substrates. OC43 and HKU1, however, lost HE lectin function as an adaptation to humans. Replaying OC43 evolution, we knocked out BCoV HE lectin function and performed forced evolution-population dynamics analysis. Loss of HE receptor binding selected for second-site mutations in S, decreasing S binding affinity by orders of magnitude. Irreversible HE mutations led to cooperativity in virus swarms with low-affinity S minority variants sustaining propagation of high-affinity majority phenotypes. Salvageable HE mutations induced successive second-site substitutions in both S and HE. Apparently, S and HE are functionally interdependent and coevolve to optimize the balance between attachment and release. This mechanism of glycan-based receptor usage, entailing a concerted, fine-tuned activity of two envelope protein species, is unique among CoVs, but reminiscent of that of influenza A viruses. Apparently, general principles fundamental to virion-sialoglycan interactions prompted convergent evolution of two important groups of human and animal pathogens.
Palabras clave
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Virión
/
Proteínas Virales de Fusión
/
Coronavirus
/
Glicoproteína de la Espiga del Coronavirus
/
Hemaglutininas Virales
Tipo de estudio:
Estudio experimental
/
Ensayo controlado aleatorizado
Tópicos:
Variantes
Idioma:
Inglés
Revista:
Proc Natl Acad Sci U S A
Año:
2020
Tipo del documento:
Artículo
País de afiliación:
Pnas.2006299117
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