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

© The Author(s) 2024. Published by Oxford University Press..

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.

Medienart:	E-Artikel

Erscheinungsjahr:	2024
Erschienen:	2024

Enthalten in:	Zur Gesamtaufnahme - volume:10
Enthalten in:	Virus evolution - 10(2024), 1 vom: 19., Seite veae006

Sprache:	Englisch

Beteiligte Personen:	Korosec, Chapin S [VerfasserIn] Wahl, Lindi M [VerfasserIn] Heffernan, Jane M [VerfasserIn]

Links:	Volltext

Themen:	Bottleneck dynamics COVID-19 De novo mutations Evolution of immune escape Journal Article SARS-CoV-2 Transmission dynamics Variants of concern Viral evolution Viral evolvability Virus evolutionary dynamics Virus life history evolution

Anmerkungen:	Date Revised 02.03.2024 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE

doi:	10.1093/ve/veae006

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	NLM369153685