SARS-CoV-2 variant of concern fitness and adaptation in primary human airway epithelia

Rita M. Meganck; Caitlin E. Edwards; Michael L. Mallory; Rhianna E. Lee; Hong Dang; Alexis B. Bailey; Jason A. Wykoff; Samuel C. Gallant; Deanna R. Zhu; Boyd L. Yount; Takafumi Kato; Kendall M. Shaffer; Satoko Nakano; Anne Marie Cawley; Vishwaraj Sontake; Jeremy R. Wang; Robert S. Hagan; Melissa B. Miller; Purushothama Rao Tata; Scott H. Randell; Longping V. Tse; Camille Ehre; Kenichi Okuda; Richard C. Boucher; Ralph S. Baric

Cell Reports (Apr 2024)

SARS-CoV-2 variant of concern fitness and adaptation in primary human airway epithelia

Rita M. Meganck,
Caitlin E. Edwards,
Michael L. Mallory,
Rhianna E. Lee,
Hong Dang,
Alexis B. Bailey,
Jason A. Wykoff,
Samuel C. Gallant,
Deanna R. Zhu,
Boyd L. Yount,
Takafumi Kato,
Kendall M. Shaffer,
Satoko Nakano,
Anne Marie Cawley,
Vishwaraj Sontake,
Jeremy R. Wang,
Robert S. Hagan,
Melissa B. Miller,
Purushothama Rao Tata,
Scott H. Randell,
Longping V. Tse,
Camille Ehre,
Kenichi Okuda,
Richard C. Boucher,
Ralph S. Baric

Affiliations

Rita M. Meganck: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Caitlin E. Edwards: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Michael L. Mallory: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Rhianna E. Lee: Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Hong Dang: Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Alexis B. Bailey: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Jason A. Wykoff: Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Samuel C. Gallant: Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Deanna R. Zhu: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Boyd L. Yount: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Takafumi Kato: Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Kendall M. Shaffer: Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Satoko Nakano: Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Anne Marie Cawley: Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Vishwaraj Sontake: Department of Cell Biology, Duke University, Durham, NC 27710, USA
Jeremy R. Wang: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Robert S. Hagan: 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
Melissa B. Miller: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Purushothama Rao Tata: Department of Cell Biology, Duke University, Durham, NC 27710, USA
Scott H. Randell: Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Longping V. Tse: Department of Molecular Microbiology & Immunology, Saint Louis University, St. Louis, MO 63104, USA
Camille Ehre: Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Kenichi Okuda: Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Richard C. Boucher: Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Ralph S. Baric: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA; Corresponding author

Journal volume & issue: Vol. 43, no. 4
p. 114076

Abstract

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Summary: 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.

CP: Microbiology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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