Evolutionary stability of antigenically escaping viruses

TL;DR

This paper models how immune response characteristics influence the evolution of mutation rates and virulence in antigenically escaping viruses, revealing different evolutionary strategies depending on immune cross-reactivity levels.

Contribution

It introduces a traveling wave model that links immune cross-reactivity to viral evolution, clarifying how mutation rates and virulence are selected in different immune environments.

Findings

Low cross-reactivity favors high mutation rates and virulence.

High cross-reactivity leads to lower mutation rates and virulence.

The model explains differences in viral evolution strategies like influenza.

Abstract

Antigenic variation is the main immune escape mechanism for RNA viruses like influenza or SARS-CoV-2. While high mutation rates promote antigenic escape, they also induce large mutational loads and reduced fitness. It remains unclear how this cost-benefit trade-off selects the mutation rate of viruses. Using a traveling wave model for the co-evolution of viruses and host immune systems in a finite population, we investigate how immunity affects the evolution of the mutation rate and other non-antigenic traits, such as virulence. We first show that the nature of the wave depends on how cross-reactive immune systems are, reconciling previous approaches. The immune-virus system behaves like a Fisher wave at low cross-reactivities, and like a fitness wave at high cross-reactivities. These regimes predict different outcomes for the evolution of non-antigenic traits. At low cross-reactivities, the evolutionarily stable strategy is to maximize the speed of the wave, implying a higher mutation rate and increased virulence. At large cross-reactivities, where our estimates place H3N2 influenza, the stable strategy is to increase the basic reproductive number, keeping the mutation rate to a minimum and virulence low.