Positive selection underlies repeated knockout of ORF8 in SARS-CoV-2 evolution.

Autor: Wagner C; Department of Genome Sciences, University of Washington, Seattle, WA, USA. cassiasw@uw.edu.; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. cassiasw@uw.edu., Kistler KE; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Howard Hughes Medical Institute, Seattle, WA, USA., Perchetti GA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Baker N; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Frisbie LA; Washington State Department of Health, Shoreline, WA, USA., Torres LM; Washington State Department of Health, Shoreline, WA, USA., Aragona F; Washington State Department of Health, Shoreline, WA, USA., Yun C; Washington State Department of Health, Shoreline, WA, USA., Figgins M; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Department of Applied Mathematics, University of Washington, Seattle, WA, USA., Greninger AL; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Cox A; Washington State Department of Health, Shoreline, WA, USA., Oltean HN; Washington State Department of Health, Shoreline, WA, USA., Roychoudhury P; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Bedford T; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Howard Hughes Medical Institute, Seattle, WA, USA.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Apr 13; Vol. 15 (1), pp. 3207. Date of Electronic Publication: 2024 Apr 13.
DOI: 10.1038/s41467-024-47599-5
Abstrakt: Knockout of the ORF8 protein has repeatedly spread through the global viral population during SARS-CoV-2 evolution. Here we use both regional and global pathogen sequencing to explore the selection pressures underlying its loss. In Washington State, we identified transmission clusters with ORF8 knockout throughout SARS-CoV-2 evolution, not just on novel, high fitness viral backbones. Indeed, ORF8 is truncated more frequently and knockouts circulate for longer than for any other gene. Using a global phylogeny, we find evidence of positive selection to explain this phenomenon: nonsense mutations resulting in shortened protein products occur more frequently and are associated with faster clade growth rates than synonymous mutations in ORF8. Loss of ORF8 is also associated with reduced clinical severity, highlighting the diverse clinical impacts of SARS-CoV-2 evolution.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: