tetano
Editor, Senior Moderator
PLoS Pathog
. 2021 Apr 8;17(4):e1009431.
doi: 10.1371/journal.ppat.1009431. eCollection 2021 Apr.
High-throughput, single-copy sequencing reveals SARS-CoV-2 spike variants coincident with mounting humoral immunity during acute COVID-19
Sung Hee Ko[SUP] 1 [/SUP], Elham Bayat Mokhtari[SUP] 1 [/SUP], Prakriti Mudvari[SUP] 1 [/SUP], Sydney Stein[SUP] 2 3 [/SUP], Christopher D Stringham[SUP] 1 [/SUP], Danielle Wagner[SUP] 1 [/SUP], Sabrina Ramelli[SUP] 2 [/SUP], Marcos J Ramos-Benitez[SUP] 2 3 [/SUP], Jeffrey R Strich[SUP] 2 [/SUP], Richard T Davey Jr[SUP] 3 [/SUP], Tongqing Zhou[SUP] 1 [/SUP], John Misasi[SUP] 1 [/SUP], Peter D Kwong[SUP] 1 [/SUP], Daniel S Chertow[SUP] 2 3 [/SUP], Nancy J Sullivan[SUP] 1 [/SUP], Eli A Boritz[SUP] 1 [/SUP]
Affiliations
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.
. 2021 Apr 8;17(4):e1009431.
doi: 10.1371/journal.ppat.1009431. eCollection 2021 Apr.
High-throughput, single-copy sequencing reveals SARS-CoV-2 spike variants coincident with mounting humoral immunity during acute COVID-19
Sung Hee Ko[SUP] 1 [/SUP], Elham Bayat Mokhtari[SUP] 1 [/SUP], Prakriti Mudvari[SUP] 1 [/SUP], Sydney Stein[SUP] 2 3 [/SUP], Christopher D Stringham[SUP] 1 [/SUP], Danielle Wagner[SUP] 1 [/SUP], Sabrina Ramelli[SUP] 2 [/SUP], Marcos J Ramos-Benitez[SUP] 2 3 [/SUP], Jeffrey R Strich[SUP] 2 [/SUP], Richard T Davey Jr[SUP] 3 [/SUP], Tongqing Zhou[SUP] 1 [/SUP], John Misasi[SUP] 1 [/SUP], Peter D Kwong[SUP] 1 [/SUP], Daniel S Chertow[SUP] 2 3 [/SUP], Nancy J Sullivan[SUP] 1 [/SUP], Eli A Boritz[SUP] 1 [/SUP]
Affiliations
- PMID: 33831133
- DOI: 10.1371/journal.ppat.1009431
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.