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SARS-CoV-2 variant of concern fitness and adaptation in primary human airway epithelia.
Meganck, Rita M; Edwards, Caitlin E; Mallory, Michael L; Lee, Rhianna E; Dang, Hong; Bailey, Alexis B; Wykoff, Jason A; Gallant, Samuel C; Zhu, Deanna R; Yount, Boyd L; Kato, Takafumi; Shaffer, Kendall M; Nakano, Satoko; Cawley, Anne Marie; Sontake, Vishwaraj; Wang, Jeremy R; Hagan, Robert S; Miller, Melissa B; Tata, Purushothama Rao; Randell, Scott H; Tse, Longping V; Ehre, Camille; Okuda, Kenichi; Boucher, Richard C; Baric, Ralph S.
Afiliação
  • Meganck RM; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Edwards CE; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Mallory ML; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Lee RE; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Dang H; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Bailey AB; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Wykoff JA; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Gallant SC; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Zhu DR; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Yount BL; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Kato T; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Shaffer KM; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Nakano S; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Cawley AM; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Sontake V; Department of Cell Biology, Duke University, Durham, NC 27710, USA.
  • Wang JR; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Hagan RS; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA; Division of Pulmonary Diseases and Critical Care Medicine, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Miller MB; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Tata PR; Department of Cell Biology, Duke University, Durham, NC 27710, USA.
  • Randell SH; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Tse LV; Department of Molecular Microbiology & Immunology, Saint Louis University, St. Louis, MO 63104, USA.
  • Ehre C; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Okuda K; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Boucher RC; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Baric RS; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA. Electronic address: rbaric@email.unc.edu.
Cell Rep ; 43(4): 114076, 2024 Apr 23.
Article em En | MEDLINE | ID: mdl-38607917
ABSTRACT
The severe acute respiratory syndrome coronavirus 2 pandemic is characterized by the emergence of novel variants of concern (VOCs) that replace ancestral strains. Here, we dissect the complex selective pressures by evaluating variant fitness and adaptation in human respiratory tissues. We evaluate viral properties and host responses to reconstruct forces behind D614G through Omicron (BA.1) emergence. We observe differential replication in airway epithelia, differences in cellular tropism, and virus-induced cytotoxicity. D614G accumulates the most mutations after infection, supporting zoonosis and adaptation to the human airway. We perform head-to-head competitions and observe the highest fitness for Gamma and Delta. Under these conditions, RNA recombination favors variants encoding the B.1.617.1 lineage 3' end. Based on viral growth kinetics, Alpha, Gamma, and Delta exhibit increased fitness compared to D614G. In contrast, the global success of Omicron likely derives from increased transmission and antigenic variation. Our data provide molecular evidence to support epidemiological observations of VOC emergence.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: SARS-CoV-2 / COVID-19 Limite: Animals / Humans Idioma: En Revista: Cell Rep Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: SARS-CoV-2 / COVID-19 Limite: Animals / Humans Idioma: En Revista: Cell Rep Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
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