0000000000685361
AUTHOR
Ernesto Segredo-otero
Genetic complementation fosters evolvability in complex fitness landscapes
Abstract The ability of natural selection to optimize traits depends on the topology of the genotype-fitness map (fitness landscape). Epistatic interactions produce rugged fitness landscapes, where adaptation is constrained by the presence of low-fitness intermediates. Here, we used simulations to explore how evolvability in rugged fitness landscapes is influenced by genetic complementation, a process whereby different sequence variants can compensate for their deleterious mutations. We designed our model inspired by viral populations, in which genetic variants are known to interact frequently through coinfection. Our simulations indicate that genetic complementation enables a more efficien…
The role of spatial structure in the evolution of viral innate immunity evasion: A diffusion-reaction cellular automaton model
Most viruses have evolved strategies for preventing interferon (IFN) secretion and evading innate immunity. Recent work has shown that viral shutdown of IFN secretion can be viewed as a social trait, since the ability of a given virus to evade IFN-mediated immunity depends on the phenotype of neighbor viruses. Following this idea, we investigate the role of spatial structure in the evolution of innate immunity evasion. For this, we model IFN signaling and viral spread using a spatially explicit approximation that combines a diffusion-reaction model and cellular automaton. Our results indicate that the benefits of preventing IFN secretion for a virus are strongly determined by spatial struct…
The effect of genetic complementation on the fitness and diversity of viruses spreading as collective infectious units
Viruses can spread collectively using different types of structures such as extracellular vesicles, virion aggregates, polyploid capsids, occlusion bodies, and even cells that accumulate virions at their surface, such as bacteria and dendritic cells. Despite the mounting evidence for collective spread, its implications for viral fitness and diversity remain poorly understood. It has been postulated that, by increasing the cellular multiplicity of infection, collective spread could enable mutually beneficial interactions among different viral genetic variants. One such interaction is genetic complementation, whereby deleterious mutations carried by different genomes are compensated. Here, we…
Social evolution of innate immunity evasion in a virus
Antiviral immunity has been studied extensively from the perspective of virus−cell interactions, yet the role of virus−virus interactions remains poorly addressed. Here, we demonstrate that viral escape from interferon (IFN)-based innate immunity is a social process in which IFN-stimulating viruses determine the fitness of neighbouring viruses. We propose a general and simple social evolution framework to analyse how natural selection acts on IFN shutdown and validate it in cell cultures and mice infected with vesicular stomatitis virus. Furthermore, we find that IFN shutdown is costly because it reduces short-term viral progeny production, thus fulfilling the definition of an altruistic tr…