Evidence for adaptive evolution in the receptor-binding domain of seasonal coronaviruses OC43 and 229E

  1. Kathryn E Kistler  Is a corresponding author
  2. Trevor Bedford
  1. University of Washington, United States
  2. Fred Hutchinson Cancer Research Center, United States

Abstract

Seasonal coronaviruses (OC43, 229E, NL63 and HKU1) are endemic to the human population, regularly infecting and reinfecting humans while typically causing asymptomatic to mild respiratory infections. It is not known to what extent reinfection by these viruses is due to waning immune memory or antigenic drift of the viruses. Here, we address the influence of antigenic drift on immune evasion of seasonal coronaviruses. We provide evidence that at least two of these viruses, OC43 and 229E, are undergoing adaptive evolution in regions of the viral spike protein that are exposed to human humoral immunity. This suggests that reinfection may be due, in part, to positively-selected genetic changes in these viruses that enable them to escape recognition by the immune system. It is possible that, as with seasonal influenza, these adaptive changes in antigenic regions of the virus would necessitate continual reformulation of a vaccine made against them.

Data availability

All data used in this study can be found at https://www.viprbrc.org/ or in the Github repository for this project: https://github.com/blab/seasonal-cov-adaptive-evolution.

Article and author information

Author details

  1. Kathryn E Kistler

    Molecular and Cellular Biology, University of Washington, Seattle, United States
    For correspondence
    kistlerk@uw.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3216-0020
  2. Trevor Bedford

    Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4039-5794

Funding

National Science Foundation (Graduation Research Fellowship Program,DGE-1762114)

  • Kathryn E Kistler

Pew Charitable Trusts (Pew Biomedical Scholar,NIH R35 GM119774-01)

  • Trevor Bedford

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Daniel B Weissman, Emory University, United States

Publication history

  1. Received: October 31, 2020
  2. Accepted: December 12, 2020
  3. Accepted Manuscript published: January 19, 2021 (version 1)
  4. Version of Record published: February 4, 2021 (version 2)

Copyright

© 2021, Kistler & Bedford

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Kathryn E Kistler
  2. Trevor Bedford
(2021)
Evidence for adaptive evolution in the receptor-binding domain of seasonal coronaviruses OC43 and 229E
eLife 10:e64509.
https://doi.org/10.7554/eLife.64509
  1. Further reading

Further reading

    1. Evolutionary Biology
    2. Medicine
    Jingsong Zhang et al.
    Research Article

    Background:

    Abiraterone acetate is an effective treatment for metastatic castrate-resistant prostate cancer (mCRPC), but evolution of resistance inevitably leads to progression. We present a pilot study in which abiraterone dosing is guided by evolution-informed mathematical models to delay onset of resistance.

    Methods:

    In the study cohort, abiraterone was stopped when PSA was <50% of pretreatment value and resumed when PSA returned to baseline. Results are compared to a contemporaneous cohort who had >50% PSA decline after initial abiraterone administration and met trial eligibility requirements but chose standard of care (SOC) dosing.

    Results:

    17 subjects were enrolled in the adaptive therapy group and 16 in the SOC group. All SOC subjects have progressed, but four patients in the study cohort remain stably cycling (range 53–70 months). The study cohort had significantly improved median time to progression (TTP; 33.5 months; p<0.001) and median overall survival (OS; 58.5 months; hazard ratio, 0.41, 95% confidence interval (CI), 0.20–0.83, p<0.001) compared to 14.3 and 31.3 months in the SOC cohort. On average, study subjects received no abiraterone during 46% of time on trial. Longitudinal trial data demonstrated the competition coefficient ratio (αRSSR) of sensitive and resistant populations, a critical factor in intratumoral evolution, was two- to threefold higher than pre-trial estimates. Computer simulations of intratumoral evolutionary dynamics in the four long-term survivors found that, due to the larger value for αRSSR, cycled therapy significantly decreased the resistant population. Simulations in subjects who progressed predicted further increases in OS could be achieved with prompt abiraterone withdrawal after achieving 50% PSA reduction.

    Conclusions:

    Incorporation of evolution-based mathematical models into abiraterone monotherapy for mCRPC significantly increases TTP and OS. Computer simulations with updated parameters from longitudinal trial data can estimate intratumoral evolutionary dynamics in each subject and identify strategies to improve outcomes.

    Funding:

    Moffitt internal grants and NIH/NCI U54CA143970-05 (Physical Science Oncology Network).

    1. Epidemiology and Global Health
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    Mobile genetic elements (MGEs) are agents of horizontal gene transfer in bacteria, but can also be vertically inherited by daughter cells. Establishing the dynamics that led to contemporary patterns of MGEs in bacterial genomes is central to predicting the emergence and evolution of novel and resistant pathogens. Methicillin-resistant Staphylococcus aureus (MRSA) clonal-complex (CC) 398 is the dominant MRSA in European livestock and a growing cause of human infections. Previous studies have identified three categories of MGEs whose presence or absence distinguishes livestock-associated CC398 from a closely related and less antibiotic-resistant human-associated population. Here, we fully characterise the evolutionary dynamics of these MGEs using a collection of 1180 CC398 genomes, sampled from livestock and humans, over 27 years. We find that the emergence of livestock-associated CC398 coincided with the acquisition of a Tn916 transposon carrying a tetracycline resistance gene, which has been stably inherited for 57 years. This was followed by the acquisition of a type V SCCmec that carries methicillin, tetracycline, and heavy metal resistance genes, which has been maintained for 35 years, with occasional truncations and replacements with type IV SCCmec. In contrast, a class of prophages that carry a human immune evasion gene cluster and that are largely absent from livestock-associated CC398 have been repeatedly gained and lost in both human- and livestock-associated CC398. These contrasting dynamics mean that when livestock-associated MRSA is transmitted to humans, adaptation to the human host outpaces loss of antibiotic resistance. In addition, the stable inheritance of resistance-associated MGEs suggests that the impact of ongoing reductions in antibiotic and zinc oxide use in European farms on livestock-associated MRSA will be slow to be realised.