Intranasal infection of ferrets with sars-cov-2 as a model for asymptomatic human infection

Helen E. Everett, Fabian Z.X. Lean, Alexander M.P. Byrne, Pauline M. van Diemen, Shelley Rhodes, Joe James, Benjamin Mollett, Vivien J. Coward, Paul Skinner, Caroline J. Warren, Kevin R. Bewley, Samantha Watson, Shellene Hurley, Kathryn A. Ryan, Yper Hall, Hugh Simmons, Alejandro Núñez, Miles Carroll, Ian H. Brown, Sharon M. Brookes

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Ferrets were experimentally inoculated with SARS-CoV-2 (severe acute respiratory syndrome (SARS)-related coronavirus 2) to assess infection dynamics and host response. During the resulting subclinical infection, viral RNA was monitored between 2 and 21 days post-inoculation (dpi), and reached a peak in the upper respiratory cavity between 4 and 6 dpi. Viral genomic sequence analysis in samples from three animals identified the Y453F nucleotide substitution relative to the inoculum. Viral RNA was also detected in environmental samples, specifically in swabs of ferret fur. Microscopy analysis revealed viral protein and RNA in upper respiratory tract tissues, notably in cells of the respiratory and olfactory mucosae of the nasal turbinates, including olfactory neuronal cells. Antibody responses to the spike and nucleoprotein were detected from 21 dpi, but virus-neutralizing activity was low. A second intranasal inoculation (re-exposure) of two ferrets after a 17-day interval did not produce re-initiation of viral RNA shedding, but did amplify the humoral response in one animal. Therefore, ferrets can be experimentally infected with SARS-CoV-2 to model human asymptomatic infection.

Original languageEnglish
Article number113
Number of pages14
JournalViruses
Volume13
Issue number1
DOIs
Publication statusPublished - Jan 2021

Bibliographical note

Funding Information:
Funding: This study was funded by the UK Department for Environment, Food & Rural Affairs (DEFRA) and the devolved Scottish and Welsh administrations, Grant numbers SE0557 and SV3700. The funder had no role in study design, analysis, interpretation or writing of this article. A virus isolate was obtained through the European Virus Archive GLOBAL (EVA-GLOBAL) project that has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 871029.

Funding Information:
Acknowledgments: We greatly appreciate Public Health England, United Kingdom and the Victorian Infectious Diseases Reference Laboratory (VIDRL) and the Peter Doherty Institute, Australia (Julian Druce) for sharing the virus isolate SARS-CoV-2/human/Australia/VIC01/2020. We would like to thank Erasmus Medical Centre, Netherlands (Bart Haagmans and Mart Lamers) for sharing knowledge on pathology techniques. We thank Andy Lane at The Native Antigen Company, Kidlington, Oxford, UK (for the provision of recombinant Covid-19 antigens. The SARS-CoV-2/human/Italy/LAZ-INMI1-isl/2020 isolate was kindly provided by the Italian Institute for Infectious Diseases (INMI) through the European Virus Archive GLOBAL (EVA-GLOBAL) project.

Funding Information:
This study was funded by the UK Department for Environment, Food & Rural Affairs (DEFRA) and the devolved Scottish and Welsh administrations, Grant numbers SE0557 and SV3700. The funder had no role in study design, analysis, interpretation or writing of this article. A virus isolate was obtained through the European Virus Archive GLOBAL (EVA-GLOBAL) project that has received funding from the European Union?s Horizon 2020 research and innovation programme under grant agreement No 871029. We greatly appreciate Public Health England, United Kingdom and the Victorian Infectious Diseases Reference Laboratory (VIDRL) and the Peter Doherty Institute, Australia (Julian Druce) for sharing the virus isolate SARS-CoV-2/human/Australia/VIC01/2020. We would like to thank Erasmus Medical Centre, Netherlands (Bart Haagmans and Mart Lamers) for sharing knowledge on pathology techniques. We thank Andy Lane at The Native Antigen Company, Kidlington, Oxford, UK (for the provision of recombinant Covid-19 antigens. The SARSCoV-2/human/Italy/LAZ-INMI1-isl/2020 isolate was kindly provided by the Italian Institute for Infectious Diseases (INMI) through the European Virus Archive GLOBAL (EVA-GLOBAL) project.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Ferret
  • Olfactory neuronal cells
  • SARS-CoV-2
  • Y453F

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