High-throughput, single-copy sequencing reveals SARS-CoV-2 spike variants coincident with mounting humoral immunity during acute COVID-19.
PLoS Pathog
; 17(4): e1009431, 2021 04.
Artículo
en Inglés
| MEDLINE | ID: covidwho-1172888
Preprint
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
Tracking evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within infected individuals will help elucidate coronavirus disease 2019 (COVID-19) pathogenesis and inform use of antiviral interventions. In this study, we developed an approach for sequencing the region encoding the SARS-CoV-2 virion surface proteins from large numbers of individual virus RNA genomes per sample. We applied this approach to the WA-1 reference clinical isolate of SARS-CoV-2 passaged in vitro and to upper respiratory samples from 7 study participants with COVID-19. SARS-CoV-2 genomes from cell culture were diverse, including 18 haplotypes with non-synonymous mutations clustered in the spike NH2-terminal domain (NTD) and furin cleavage site regions. By contrast, cross-sectional analysis of samples from participants with COVID-19 showed fewer virus variants, without structural clustering of mutations. However, longitudinal analysis in one individual revealed 4 virus haplotypes bearing 3 independent mutations in a spike NTD epitope targeted by autologous antibodies. These mutations arose coincident with a 6.2-fold rise in serum binding to spike and a transient increase in virus burden. We conclude that SARS-CoV-2 exhibits a capacity for rapid genetic adaptation that becomes detectable in vivo with the onset of humoral immunity, with the potential to contribute to delayed virologic clearance in the acute setting.
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Inmunidad Humoral
/
Glicoproteína de la Espiga del Coronavirus
/
SARS-CoV-2
/
COVID-19
/
Mutación
/
Epítopos
Tipo de estudio:
Estudio observacional
/
Estudio pronóstico
/
Ensayo controlado aleatorizado
Tópicos:
Variantes
Límite:
Femenino
/
Humanos
/
Masculino
Idioma:
Inglés
Revista:
PLoS Pathog
Año:
2021
Tipo del documento:
Artículo
País de afiliación:
Journal.ppat.1009431
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