Evaluating the within-host fitness effects of mutations fixed during virus adaptation to different ecotypes of a new host

Abstract

One contribution of 17 to a theme issue 'Within-host dynamics of infection: from ecological insights to evolutionary predictions'. The existence of genetic variation for resistance in host populations is assumed to be essential to the spread of an emerging virus. Models predict that the rate of spread slows down with the increasing frequency and higher diversity of resistance alleles in the host population. We have been using the experimental pathosystem Arabidopsis thaliana-tobacco etch potyvirus (TEV) to explore the interplay between genetic variation in host's susceptibility and virus diversity. We have recently shown that TEV populations evolving in A. thaliana ecotypes that differ in susceptibility to infection gained within-host fitness, virulence and infectivity in a manner compatible with a gene-for-gene model of host-parasite interactions: hard-to-infect ecotypes were infected by generalist viruses, whereas easy-to-infect ecotypes were infected by every virus. We characterized the genomes of the evolved viruses and found cases of host-driven convergent mutations. To gain further insights in the mechanistic basis of this gene-for-gene model, we have generated all viral mutations individually as well as in specific combinations and tested their within-host fitness effects across ecotypes. Most of these mutations were deleterious or neutral in their local ecotype and only a very reduced number had a hostspecific beneficial effect. We conclude that most of the mutations fixed during the evolution experiment were so by drift or by selective sweeps along with the selected driver mutation. In addition, we evaluated the ruggedness of the underlying adaptive fitness landscape and found that mutational effects were mostly multiplicative, with few cases of significant epistasis.

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

“…Some readers may consider the following to be caveats of this study: (i) A. thaliana is not a natural host of TEV, and (ii) all our experiments were performed under controlled greenhouse conditions that may be optimal for virus replication and accumulation. We do not consider the first to be a real problem, as this study, and all previous ones performed with the same experimental pathosystem (25,26,30,(55)(56)(57)(58)(59), deal with the evolutionary determinants and consequences of viral emergence and adaptation to a fully novel host. The second may certainly be an issue to be considered.…”

Evolutionary transitions during RNA virus experimental evolution

“…The severity of symptoms induced varies widely between species and even between varieties of the same species: from vein clearing, mottling, necrotic etching and plant stunting to less severe symptoms. In a series of evolution experiments [5][6][7][8][9][10][11], we have explored the ability of TEV to expand its host range to a new species that is completely outside its natural host range, the brassica Arabidopsis thaliana ecotype Ler-0. Brassicaceae belong to a different order than Solanaceae within the class Magnoliopsida, hence, adaptation of TEV to A. thaliana represents a jump in host species at the taxonomic level of orders.…”

Synonymous Co-Variation across the E1/E2 Gene Junction of Hepatitis C Virus Defines Virion Fitness

“…The perception that synonymous change equates to ‘silent’ change is false [9, 10, 12, 40]. In this report, we add to observations that synonymous substitutions occurring amongst related viral variants may hold answers with respect to viral fitness and evolutionary strategies [9, 14, 41].…”

“…HIV-1 treatment resistance mutations have been observed to occur in tandem with subsequent compensatory mutations to correct for consequential loss of fitness [11]. A number of studies have indicated that significant fitness effects can result solely as a consequence of synonymous mutation [10, 12–14]. …”