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Comparison of SARS-CoV-2 Evolution in Paediatric Primary Airway Epithelial Cell Cultures Compared with Vero-Derived Cell Lines.
Bamford, Connor G G; Broadbent, Lindsay; Aranday-Cortes, Elihu; McCabe, Mary; McKenna, James; Courtney, David G; Touzelet, Olivier; Ali, Ahlam; Roberts, Grace; Lopez Campos, Guillermo; Simpson, David; McCaughey, Conall; Fairley, Derek; Mills, Ken; Power, Ultan F.
  • Bamford CGG; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast BT9 7BL, UK.
  • Broadbent L; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast BT9 7BL, UK.
  • Aranday-Cortes E; Medical Research Council-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK.
  • McCabe M; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast BT9 7BL, UK.
  • McKenna J; Regional Virus Laboratory, Belfast Health and Social Care Trust, Belfast BT12 6BA, UK.
  • Courtney DG; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast BT9 7BL, UK.
  • Touzelet O; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast BT9 7BL, UK.
  • Ali A; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast BT9 7BL, UK.
  • Roberts G; Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast BT9 7AE, UK.
  • Lopez Campos G; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast BT9 7BL, UK.
  • Simpson D; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast BT9 7BL, UK.
  • McCaughey C; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast BT9 7BL, UK.
  • Fairley D; Regional Virus Laboratory, Belfast Health and Social Care Trust, Belfast BT12 6BA, UK.
  • Mills K; Regional Virus Laboratory, Belfast Health and Social Care Trust, Belfast BT12 6BA, UK.
  • Power UF; Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast BT9 7AE, UK.
  • On Behalf Of The Breathing Together Investigators; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast BT9 7BL, UK.
Viruses ; 14(2)2022 02 05.
Article in English | MEDLINE | ID: covidwho-1674824
ABSTRACT
SARS-CoV-2 can efficiently infect both children and adults, albeit with morbidity and mortality positively associated with increasing host age and presence of co-morbidities. SARS-CoV-2 continues to adapt to the human population, resulting in several variants of concern (VOC) with novel properties, such as Alpha and Delta. However, factors driving SARS-CoV-2 fitness and evolution in paediatric cohorts remain poorly explored. Here, we provide evidence that both viral and host factors co-operate to shape SARS-CoV-2 genotypic and phenotypic change in primary airway cell cultures derived from children. Through viral whole-genome sequencing, we explored changes in genetic diversity over time of two pre-VOC clinical isolates of SARS-CoV-2 during passage in paediatric well-differentiated primary nasal epithelial cell (WD-PNEC) cultures and in parallel, in unmodified Vero-derived cell lines. We identified a consistent, rich genetic diversity arising in vitro, variants of which could rapidly rise to near fixation within two passages. Within isolates, SARS-CoV-2 evolution was dependent on host cells, with paediatric WD-PNECs showing a reduced diversity compared to Vero (E6) cells. However, mutations were not shared between strains. Furthermore, comparison of both Vero-grown isolates on WD-PNECs disclosed marked growth attenuation mapping to the loss of the polybasic cleavage site (PBCS) in Spike, while the strain with mutations in Nsp12 (T293I), Spike (P812R) and a truncation of Orf7a remained viable in WD-PNECs. Altogether, our work demonstrates that pre-VOC SARS-CoV-2 efficiently infects paediatric respiratory epithelial cells, and its evolution is restrained compared to Vero (E6) cells, similar to the case of adult cells. We highlight the significant genetic plasticity of SARS-CoV-2 while uncovering an influential role for collaboration between viral and host cell factors in shaping viral evolution and ultimately fitness in human respiratory epithelium.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Evolution, Molecular / Respiratory Mucosa / SARS-CoV-2 Type of study: Cohort study / Observational study / Prognostic study Topics: Variants Limits: Animals / Child / Humans Language: English Year: 2022 Document Type: Article Affiliation country: V14020325

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Evolution, Molecular / Respiratory Mucosa / SARS-CoV-2 Type of study: Cohort study / Observational study / Prognostic study Topics: Variants Limits: Animals / Child / Humans Language: English Year: 2022 Document Type: Article Affiliation country: V14020325