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Updated: Jun 28, 2025
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In Vitro Selection of Aptamers to Differentiate Infectious from Non-Infectious Viruses
Published on: September 7, 2022
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Positive selection underlies repeated knockout of ORF8 in SARS-CoV-2 evolution.
Cassia Wagner1,2, Kathryn E Kistler3,4, Garrett A Perchetti5
1Department of Genome Sciences, University of Washington, Seattle, WA, USA. cassiasw@uw.edu.
Nature Communications
|April 13, 2024
Summary
The loss of the ORF8 protein in SARS-CoV-2, the virus that causes COVID-19, has become common due to positive selection. This viral evolution is linked to reduced disease severity.
Area of Science:
- Virology
- Evolutionary Biology
- Genomics
Background:
- The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has undergone significant evolution since its emergence.
- The ORF8 protein is a accessory protein known to be rapidly evolving and frequently deleted in SARS-CoV-2 variants.
Purpose of the Study:
- To investigate the evolutionary pressures driving the loss of the ORF8 protein in SARS-CoV-2.
- To understand the impact of ORF8 knockout on viral fitness and clinical severity.
Main Methods:
- Analysis of regional (Washington State) and global SARS-CoV-2 pathogen sequencing data.
- Phylogenetic analysis to identify patterns of ORF8 gene loss and selection.
- Comparison of mutation rates (nonsense vs. synonymous) and clade growth rates.
Main Results:
- ORF8 knockout events were observed throughout SARS-CoV-2 evolution, not limited to specific high-fitness viral backbones.
- ORF8 truncation occurred more frequently and persisted longer than for any other gene.
- Nonsense mutations leading to ORF8 loss showed evidence of positive selection, correlating with faster clade growth rates.
- Loss of ORF8 was associated with reduced clinical severity of COVID-19.
Conclusions:
- Positive selection favors the loss of the ORF8 protein in SARS-CoV-2.
- ORF8 knockout contributes to viral evolution and may reduce disease severity.
- Understanding ORF8's role provides insights into the diverse clinical impacts of SARS-CoV-2 evolution.
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