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Structural considerations in the fitness landscape of a virus.

ABSTRACT: Viral fitness is determined by replication within hosts and transmission between them. We examine how pleiotropic mutations that have antagonistic effects (i.e., antibody evasion vs. receptor binding) on viral replication within hosts can impact viral immune escape in the host population. When the host population is vaccinated, the virus escapes from passive immunity by mutations in the antibody-binding region on the surface of the target protein. However, the reduced ability of the antibody to bind the virus is often accompanied by a reduced ability of the virus to bind the cell receptor because the antibody-binding region overlaps with the receptor-binding domain (RBD). The types of permitted mutations are limited. To investigate the causal relation between a mutation in a viral genome and adaptive evolution of a viral population, we developed a mathematical model that describes the population dynamics of viruses, antibodies, and normal/infected cells within a host. The coefficients describe the binding affinity between the virus and the induced antibody and that between the virus and its receptor. Our knowledge-based index enables us to estimate the effect of a mutation in a binding region on the binding affinity. Using population genetic theory, we evaluated the probability that a mutant is fixed in a host population. The mutations that can be fixed with high probabilities may determine how long a vaccine remains effective. We simulate the adaptive evolution of coronavirus, the etiological agent of severe acute respiratory syndrome, and show that some of mutations in the RBD may have high fixation probabilities in the vaccinated host population.

SUBMITTER: Watabe T

PROVIDER: S-EPMC7187634 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Adaptive fitness landscapes are a fundamental concept in evolutionary biology that relate the genotypes of individuals to their fitness. In the end, the evolutionary fate of evolving populations depends on the topography of the landscape, that is, the numbers of accessible mutational pathways and possible fitness peaks (i.e., adaptive solutions). For a long time, fitness landscapes were only theoretical constructions due to a lack of precise information on the mapping between genotypes and phenotypes. In recent years, however, efforts have been devoted to characterizing the properties of empirical fitness landscapes for individual proteins or for microbes adapting to artificial environments. In a previous study, we characterized the properties of the empirical fitness landscape defined by the first five mutations fixed during adaptation of tobacco etch potyvirus (TEV) to a new experimental host, Arabidopsis thaliana Here we evaluate the topography of this landscape in the ancestral host Nicotiana tabacum By comparing the topographies of the landscapes for the two hosts, we found that some features remained similar, such as the existence of fitness holes and the prevalence of epistasis, including cases of sign and reciprocal sign epistasis that created rugged, uncorrelated, and highly random topographies. However, we also observed significant differences in the fine-grained details between the two landscapes due to changes in the fitness and epistatic interactions of some genotypes. Our results support the idea that not only fitness tradeoffs between hosts but also topographical incongruences among fitness landscapes in alternative hosts may contribute to virus specialization. IMPORTANCE Despite its importance for understanding virus evolutionary dynamics, very little is known about the topography of virus adaptive fitness landscapes, and even less is known about the effects that different host species and environmental conditions may have on this topography. To bridge this gap, we evaluated the topography of a small fitness landscape formed by all genotypes that result from every possible combination of the first five mutations fixed during adaptation of TEV to the novel host A. thaliana To assess the effect that host species may have on this topography, we evaluated the fitness of every genotype in both the ancestral and novel hosts. We found that both landscapes share some macroscopic properties, such as the existence of holes and being highly rugged and uncorrelated, yet they differ in microscopic details due to changes in the magnitude and sign of fitness and epistatic effects.

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Structural considerations in the fitness landscape of a virus.

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