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

Abstract

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...

Pleiotropic Effects of Resistance-Breaking Mutations on Particle Stability Provide Insight into Life History Evolution of a Plant RNA Virus

“…These results confirm our previous finding that deployment of resistance in the host population results in selection for resistance breaking (12) and for differential survival, a trait unrelated to the plant-virus interaction (24). As was the case for virus multiplication in susceptible hosts (25), the sense and magnitude of the pleiotropy depend on the specific mutations that determine resistance breaking and not on the pathotype. Hence, there is no trade-off in this system between increased host range (i.e., resistance breaking) and survival, as has been reported for bacteriophages (55,58).…”

“…There is abundant evidence of resistancebreaking fitness costs in plant viruses, which are expressed as reduced multiplication in susceptible host genotypes compared with the wild-type virus genotypes (11,12,14,16,25,(47)(48)(49). Evidence also indicates that a major cause of across-host fitness trade-offs in RNA viruses (1, 50-52) is antagonistic pleiotropy (53), i.e., opposite phenotypic effects of mutations in different environments.…”

“…Resistancebreaking costs were due to pleiotropic effects of resistance-breaking mutations and depended on the specific genotype of the susceptible host and the type of infection, single or mixed (25). Also, the analysis of P 0, P 1,2 , and P 1,2,3 pathotype field isolates showed that the stability of their particles differed and that the capacity to survive in the soil was positively correlated with particle stability (24).…”

“…The present work builds on previous results from our group on resistance-breaking costs, and their generating mechanisms, in the interaction between virus species in the genus Tobamovirus and pepper (Capsicum annuum L.) (12,24,25). Tobamoviruses have a single-stranded, monopartite genome encapsidated into rod-shaped particles, whose structure has been resolved by X-ray crystallography for several species (26)(27)(28).…”

“…Conclusive evidence of resistance-breaking costs, expressed as reduced virus multiplication in susceptible host genotypes, was obtained from the analysis of Spanish field isolates of TMGMV (P 0 pathotype) and PMMoV (P 1,2 and P 1,2,3 pathotypes) and of PMMoV CP mutants engineered into infectious cDNA clones (12,25). Resistancebreaking costs were due to pleiotropic effects of resistance-breaking mutations and depended on the specific genotype of the susceptible host and the type of infection, single or mixed (25).…”