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Interferon Resistance of Emerging SARS-CoV-2 Variants

Kejun Guo, Bradley S. Barrett, Kaylee L. Mickens, Kim J. Hasenkrug, View ORCID ProfileMario L. Santiago
doi: https://doi.org/10.1101/2021.03.20.436257
Kejun Guo
1Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA 80045
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Bradley S. Barrett
1Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA 80045
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Kaylee L. Mickens
1Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA 80045
2Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA 80045
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Kim J. Hasenkrug
3Rocky Mountain Laboratories, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840
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Mario L. Santiago
1Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA 80045
2Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA 80045
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  • ORCID record for Mario L. Santiago
  • For correspondence: mario.santiago@ucdenver.edu
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Abstract

The emergence of SARS-CoV-2 variants with enhanced transmissibility, pathogenesis and resistance to vaccines presents urgent challenges for curbing the COVID-19 pandemic. While Spike mutations that enhance virus infectivity may drive the emergence of these novel variants, studies documenting a critical a role for interferon responses in the early control of SARS-CoV-2 infection, combined with the presence of viral genes that limit these responses, suggest that interferons may also influence SARS-CoV-2 evolution. Here, we compared the potency of 17 different human interferons against 5 viral lineages sampled during the course of the global outbreak that included ancestral and emerging variants. Our data revealed increased interferon resistance in emerging SARS-CoV-2 variants, indicating that evasion of innate immunity is a significant driving force for SARS-CoV-2 evolution. These findings have implications for the increased lethality of emerging variants and highlight the interferon subtypes that may be most successful in the treatment of early infections.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 21, 2021.
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Interferon Resistance of Emerging SARS-CoV-2 Variants
Kejun Guo, Bradley S. Barrett, Kaylee L. Mickens, Kim J. Hasenkrug, Mario L. Santiago
bioRxiv 2021.03.20.436257; doi: https://doi.org/10.1101/2021.03.20.436257
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Interferon Resistance of Emerging SARS-CoV-2 Variants
Kejun Guo, Bradley S. Barrett, Kaylee L. Mickens, Kim J. Hasenkrug, Mario L. Santiago
bioRxiv 2021.03.20.436257; doi: https://doi.org/10.1101/2021.03.20.436257

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