COS 80-5 - Variation of Intrinsic Host Fitness Increases Likelihood of Viral Escapes in Stochastic Model of Microbe-Lytic Virus Coevolution

Abstract: Many microbial species are known to evade viral infection through their adaptive immunity obtained via the CRISPR system and CRISPR-associated (Cas) proteins. CRISPR-Cas immunity confers traits that provide sequence-specific protection against viruses. These `spacers' exhibit significant variation within and between microbes, and underlie non-trivial network structures of who infects whom, and who is protected from whom. Previous theoretical studies have examined the effect of CRISPR immune diversification and network structure on microbe-lytic virus coevolution, as the result of frequency-dependent selection with hosts typically equivalent except for their immune memory. Alongside CRISPR-mediated immunity, hosts can also possess traits that confer fixed fitness advantages. Here, we address the combined effect of both kinds of traits on the likelihood of viral escape. To this end, we develop a fully stochastic model of CRISPR-induced microbe-lytic virus coevolution wherein host fitness abides by Fisher's geometric model. We computationally examine probabilistic patterns of viral diversification, adaptation and extinction as a function of host fitness effect size, and compare the results to recent experiments by Guillemet et al. (2022).

We show an increase in both the likelihood of a viral escape and the number of viral escapes with the intensity of selection on the variation of intrinsic host fitness. The observed relationship between the intensity of selection and viral escape is found to be consistent with experiments. Furthermore, we observe that the probability of extinction of the viral population remains effectively constant as the intensity of selection is increased. We also find that the onsets of viral epidemics are correlated to declines in the expected time to the most recent common viral ancestor. Our results provide more accurate expectations for the persistence and diversity of microbe-lytic virus systems in nature and laboratory settings.