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10.1371/journal.ppat.1009431

http://scihub22266oqcxt.onion/10.1371/journal.ppat.1009431
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33831133!8031304!33831133
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suck abstract from ncbi


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pmid33831133      PLoS+Pathog 2021 ; 17 (4): e1009431
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  • High-throughput, single-copy sequencing reveals SARS-CoV-2 spike variants coincident with mounting humoral immunity during acute COVID-19 #MMPMID33831133
  • Ko SH; Bayat Mokhtari E; Mudvari P; Stein S; Stringham CD; Wagner D; Ramelli S; Ramos-Benitez MJ; Strich JR; Davey RT Jr; Zhou T; Misasi J; Kwong PD; Chertow DS; Sullivan NJ; Boritz EA
  • PLoS Pathog 2021[Apr]; 17 (4): e1009431 PMID33831133show ga
  • 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.
  • |*COVID-19/genetics/immunology[MESH]
  • |*Epitopes/genetics/immunology[MESH]
  • |*Immunity, Humoral[MESH]
  • |*Mutation[MESH]
  • |*SARS-CoV-2/genetics/immunology[MESH]
  • |*Spike Glycoprotein, Coronavirus/genetics/immunology[MESH]
  • |Cell Line[MESH]
  • |Female[MESH]
  • |High-Throughput Nucleotide Sequencing[MESH]
  • |Humans[MESH]


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