Host Alternation of Chikungunya Virus Increases Fitness while Restricting Population Diversity and Adaptability to Novel Selective Pressures

Overcoming host resistance in gene-for-gene host-virus interactions is an important instance of host range expansion, which can be hindered by across-host fitness trade-offs. Trade-offs are generated by negative effects of host range mutations on the virus fitness in the original host, i.e., by antagonistic pleiotropy. It has been reported that different mutations in Pepper mild mottle virus (PMMoV) coat protein result in overcoming L-gene resistance in pepper. To analyze if resistance-breaking mutations in PMMoV result in antagonistic pleiotropy, all reported mutations determining the overcoming of L 3 and L 4 alleles were introduced in biologically active cDNA clones. Then, the parental and mutant virus genotypes were assayed in susceptible pepper genotypes with an L ؉ , L 1 , or L 2 allele, in single and in mixed infections. Resistance-breaking mutations had pleiotropic effects on the virus fitness that, according to the specific mutation, the host genotype, and the type of infection, single or mixed with other virus genotypes, were antagonistic or positive. Thus, resistance-breaking mutations can generate fitness trade-offs both across hosts and across types of infection, and the frequency of host range mutants will depend on the genetic structure of the host population and on the frequency of mixed infections by different virus genotypes. Also, resistance-breaking mutations variously affected virulence, which may further influence the evolution of host range expansion. Changes in virus host range affect virus ecology and epidemiology, condition virus emergence, and can compromise the success of strategies for the control of viral diseases (1-4). The acquisition of new hosts, that is, host range expansion, would provide a virus with more opportunities for transmission and survival. However, differential host-associated selection may result in across-host fitness trade-offs so that increasing the virus fitness in a new host will decrease its fitness in the original one, which will hinder host range expansion (4-6). The simplest mechanism generating across-hosts fitness trade-offs is antagonistic pleiotropy, in which mutations that increase fitness in one host are deleterious in another one (7). Evidence indicates that antagonistic pleiotropy is common in RNA viruses as a result of their small genomes, which are compacted with genetic information and encode few, multifunctional proteins (5,8).Host range evolution is particularly relevant for the sustainable use of genetic resistance to control viral diseases of crops. Disease control based on resistant cultivars is target specific and highly efficient but is not durable due to the appearance of new virus genotypes able to infect otherwise resistant host genotypes. The increase in frequency of resistance-breaking virus genotypes eventually renders resistance inefficient (9-11). Plant-virus interactions can often be explained by the gene-for-gene (GFG) model, under which direct or indirect recognition of viral proteins by those encoded by plant resistan...

Section: Discussionsupporting

confidence: 69%

Mutations That Determine Resistance Breaking in a Plant RNA Virus Have Pleiotropic Effects on Its Fitness That Depend on the Host Environment and on the Type, Single or Mixed, of Infection

Moreno‐Pérez

García-Luque

Fraile

et al. 2016

“…Not all potential hosts in the host range (different species or different genotypes of the same species) of a virus are equally susceptible to infection, and it is generally assumed that a tight match may exist between host genotypes and virus genotypes to allow a virus to successfully infect a host (6). Indeed, a substantial amount of data supports the idea that by evolving in a single host species or genotype, viruses become specialists (7)(8)(9)(10), whereas by evolving in multiple host species, the result may be no-cost generalists (7,(11)(12)(13).…”

Section: Importancementioning

confidence: 78%

Effect of Host Species on Topography of the Fitness Landscape for a Plant RNA Virus

Cervera

Lalić

Elena

2016

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. IMPORTANCEDespite 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. T he effects of mutations can be influenced by their interactions with other mutations, with the environment, or both. Epistatic interactions among genetic loci determine the ruggedness of fitness landscapes. In the absence of epistasis, landscapes are single peaked and smooth (1). For such simple landscapes, predicting the result of evolution is an easy task. In contrast, epistatic interactions create curvature in the lands...

“…The need to infect both vertebrates and mosquitoes exerts evolutionary pressure on arboviruses by constraining their adaptation to a single host, presumably due to fitness tradeoffs for replication in vertebrates versus invertebrates (40)(41)(42)(43)(44)(45). In some cases, once the requirement for replication in one of the hosts is eliminated, these evolutionary con- straints are greatly reduced, and adaptation to the retained host accelerates, coinciding with a loss of fitness for infection of the abandoned host (40)(41)(42)(43)(44)(45). EILV appears to be an example of this host-specific adaptation.…”

Section: Fig 8 Predicted Secondary Structure Of Eilv (A) and Sinv (B) 3=mentioning

confidence: 99%

Eilat Virus Host Range Restriction Is Present at Multiple Levels of the Virus Life Cycle

Nasar

Gorchakov

Tesh

et al. 2015

Most alphaviruses are mosquito-borne and exhibit a broad host range, infecting many different vertebrates, including birds, rodents, equids, humans, and nonhuman primates. This ability of most alphaviruses to infect arthropods and vertebrates is essential for their maintenance in nature. Recently, a new alphavirus, Eilat virus (EILV), was described, and in contrast to all other mosquito-borne viruses, it is unable to replicate in vertebrate cell lines. Investigations into the nature of its host range restriction showed the inability of genomic EILV RNA to replicate in vertebrate cells. Here, we investigated whether the EILV host range restriction is present at the entry level and further explored the viral factors responsible for the lack of genomic RNA replication. Utilizing Sindbis virus (SINV) and EILV chimeras, we show that the EILV vertebrate host range restriction is also manifested at the entry level. Furthermore, the EILV RNA replication restriction is independent of the 3= untranslated genome region (UTR). Complementation experiments with SINV suggested that RNA replication is restricted by the inability of the EILV nonstructural proteins to form functional replicative complexes. These data demonstrate that the EILV host range restriction is multigenic, involving at least one gene from both nonstructural protein (nsP) and structural protein (sP) open reading frames (ORFs). As EILV groups phylogenetically within the mosquito-borne virus clade of pathogenic alphaviruses, our findings have important evolutionary implications for arboviruses. IMPORTANCE Our work explores the nature of host range restriction of the first "mosquito-only alphavirus," EILV. EILV is related to pathogenic mosquito-borne viruses (Eastern equine encephalitis virus [EEEV], Western equine encephalitis virus [WEEV], Venezuelan equine encephalitis virus [VEEV], and Chikungunya virus [CHIKV]) that cause severe disease in humans. Our data demonstrate that EILV is restricted both at entry and genomic RNA replication levels in vertebrate cells. These findings have important implications for arbovirus evolution and will help elucidate the viral factors responsible for the broad host range of pathogenic mosquito-borne alphaviruses, facilitate vaccine development, and inform potential strategies to reduce/prevent alphavirus transmission.A rthropod-borne viruses (arboviruses) such as dengue virus, Chikungunya virus, West Nile virus, and Rift Valley fever virus are important causes of human and animal disease worldwide (1, 2). Arboviruses encompass diverse virus families, including Togaviridae, Bunyaviridae, Flaviviridae, Rhabdoviridae, Orthomyxoviridae, Reoviridae, and Asfarviridae, and are maintained in nature primarily through biological transmission between susceptible vertebrate hosts and hematophagous arthropods such as ticks, mosquitoes, and other biting flies (1, 2). This ability to infect diverse vertebrate and arthropod hosts enables arboviruses to persist in nature; however, the viral factors that facilitate their broad host ...