Interferon resistance of emerging SARS-CoV-2 variants

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 or neutralizing antibody evasion may drive the emergence of these novel var...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2022-08, Vol.119 (32), p.e2203760119-e2203760119
Main Authors: Guo, Kejun, Barrett, Bradley S, Morrison, James H, Mickens, Kaylee L, Vladar, Eszter K, Hasenkrug, Kim J, Poeschla, Eric M, Santiago, Mario L
Format: Article
Language:English
Subjects:
Antibodies
Antibodies, Neutralizing
Antiviral Agents - pharmacology
Antiviral Agents - therapeutic use
Biological Sciences
COVID-19
COVID-19 - immunology
COVID-19 - prevention & control
COVID-19 - transmission
Evolution
Humans
Infections
Infectivity
Innate immunity
Interferon
Interferons - pharmacology
Interferons - therapeutic use
Lethality
Mutation
Pandemics
Pathogenesis
SARS-CoV-2 - drug effects
SARS-CoV-2 - genetics
SARS-CoV-2 - immunology
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
Spike Glycoprotein, Coronavirus - genetics
Vaccines
Viral diseases
Viruses
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Summary: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 or neutralizing antibody evasion may drive the emergence of these novel variants, studies documenting a critical 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 multiple viral lineages sampled during the course of the global outbreak, including ancestral and five major variants of concern that include the B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma), B.1.617.2 (delta), and B.1.1.529 (omicron) lineages. Our data reveal that relative to ancestral isolates, SARS-CoV-2 variants of concern exhibited increased interferon resistance, suggesting that evasion of innate immunity may be a significant, ongoing driving force for SARS-CoV-2 evolution. These findings have implications for the increased transmissibility and/or lethality of emerging variants and highlight the interferon subtypes that may be most successful in the treatment of early infections.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2203760119