Within-host evolution of SARS-CoV-2: how often are de novo mutations transmitted from symptomatic infections?

Autor:	Korosec CS; Modelling Infection and Immunity Lab, Mathematics and Statistics, York University, 4700 Keele St, Toronto, ON M3J 1P3, Canada.; Centre for Disease Modelling, Mathematics and Statistics, York University, 4700 Keele St, Toronto, ON M3J 1P3, Canada., Wahl LM; Applied Mathematics, Western University, 1151 Richmond St, London, ON N6A 5B7, Canada., Heffernan JM; Modelling Infection and Immunity Lab, Mathematics and Statistics, York University, 4700 Keele St, Toronto, ON M3J 1P3, Canada.; Centre for Disease Modelling, Mathematics and Statistics, York University, 4700 Keele St, Toronto, ON M3J 1P3, Canada.
Jazyk:	angličtina
Zdroj:	Virus evolution [Virus Evol] 2024 Feb 21; Vol. 10 (1), pp. veae006. Date of Electronic Publication: 2024 Feb 21 (Print Publication: 2024).
DOI:	10.1093/ve/veae006
Abstrakt:	Despite a relatively low mutation rate, the large number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has allowed for substantial genetic change, leading to a multitude of emerging variants. Using a recently determined mutation rate (per site replication), as well as within-host parameter estimates for symptomatic SARS-CoV-2 infection, we apply a stochastic transmission-bottleneck model to describe the survival probability of de novo SARS-CoV-2 mutations as a function of bottleneck size and selection coefficient. For narrow bottlenecks, we find that mutations affecting per-target-cell attachment rate (with phenotypes associated with fusogenicity and ACE2 binding) have similar transmission probabilities to mutations affecting viral load clearance (with phenotypes associated with humoral evasion). We further find that mutations affecting the eclipse rate (with phenotypes associated with reorganization of cellular metabolic processes and synthesis of viral budding precursor material) are highly favoured relative to all other traits examined. We find that mutations leading to reduced removal rates of infected cells (with phenotypes associated with innate immune evasion) have limited transmission advantage relative to mutations leading to humoral evasion. Predicted transmission probabilities, however, for mutations affecting innate immune evasion are more consistent with the range of clinically estimated household transmission probabilities for de novo mutations. This result suggests that although mutations affecting humoral evasion are more easily transmitted when they occur, mutations affecting innate immune evasion may occur more readily. We examine our predictions in the context of a number of previously characterized mutations in circulating strains of SARS-CoV-2. Our work offers both a null model for SARS-CoV-2 mutation rates and predicts which aspects of viral life history are most likely to successfully evolve, despite low mutation rates and repeated transmission bottlenecks. (© The Author(s) 2024. Published by Oxford University Press.)
Databáze:	MEDLINE
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