Biology subjects

Toft, C.

Publications and source records attributed to Toft, C..

4 recordsLinked to original sources

bioRxiv2026

Evolution of virulence of a plant RNA virus in age-diverse host populations

Natural host populations are intrinsically age-structured, and developmental stages differ in susceptibility and within-host dynamics, meaning age compositions can impose distinct selective pressure on pathogens. However, how host age structure shapes viral evolution remains largely untested. We experimentally evolved turnip mosaic virus (TuMV) for five passages in Arabidopsis thaliana populations spanning seven demographic regimes (from juvenile-dominated to mature-dominated cohorts). We quantified disease progression, symptom severity and viral load, cross-inoculated evolved lineages across host stages to build quantitative infection matrices, and performed whole-population sequencing at passages 1 and 5 to infer selection coefficients and test for parallelism. Disease traits changed strongly with passage, demography, and their interaction. Disease progression evolved faster in older host populations, whereas severity showed no detectable dependence on median age, implying demographic reweighting of virulence components. Viral load increased through passages and positively correlated with severity, linking within-host fitness to symptoms. Cross-assays revealed a non-nested but modular infection network: juvenile-evolved lineages specialized on pre-bolting plants, whereas lineages from intermediate/older demographies were more stage-generalist. Genomically, both parallel and demography-specific solutions emerged, with a dense cluster of recurrent changes in VPg and several synonymous variants showing consistent or sign-flipping selection across demographies. In conclusion, host age structure is a primary ecological driver of virulence evolution, determining whether viruses evolve faster disease timing versus stronger severity, and whether they specialize or generalize across host stages. These results integrate phenotypes with genome-level responses and suggest that manipulating crop age pyramids could steer virus evolution toward less damaging outcomes.

evolutionary biology↗

bioRxiv2024

Chronic infection of Caenorhabditis elegans by Orsay virus induces age-dependent immunity and superinfection exclusion

Orsay virus (OrV) is a natural pathogen of C. elegans, which mounts an antiviral response upon infection and enables the investigation of the mechanisms governing infection and immunity. Here, we focus on two of these features, namely the effect of life-long infections and superinfection dynamics. By following the course of an infection throughout the lifespan of a synchronous wild-type population, we describe several viral load peaks followed by sharp decreases in viral load, suggesting that the infection is chronic and that animals manage to suppress viral replication successfully throughout most of their lives. Moreover, we show that animals that have been previously exposed to the virus are able to control viral replication upon a subsequent inoculation, indicative of superinfection exclusion. Primary infections produced transcriptomic and small RNA alterations, whose extent was highly dependent on the developmental stage of the worm at the time of infection and the time until sampling. Superinfection, in turn, had little impact on the overall transcriptome, but showed a misregulation of piRNAs, rRNAs, and tsRNAs. Superinfection exclusion was robust throughout larval development and adulthood, providing protection against various OrV isolates. However, the protective effect of the initial infection diminished over time, suggesting different mechanisms of action and ultimately favoring the primary infecting virus. This phenomenon was dependent on a functional RNA interference pathway.

genomics↗

bioRxiv2024

Mapping the mutational landscape of a full viral proteome reveals distinct profiles of mutation tolerability

RNA viruses have notoriously high mutation rates due to error-prone replication by their RNA polymerase. However, natural selection concentrates variability in a few key viral proteins. To test whether this stems from different mutation tolerance profiles among viral proteins, we measured the effect of >40,000 non-synonymous mutations across the full proteome of coxsackievirus B3 as well as >97% of all codon deletions in the non-structural proteins. We find significant variation in mutational tolerance within and between individual viral proteins, which correlated with both general and protein-specific structural and functional attributes. Further, mutational fitness effects remained largely constant across cell lines, highlighting conserved selection pressures. In addition to providing a rich dataset for understanding virus biology and evolution, our results illustrate that incorporation of mutational tolerance data into druggable pocket discovery can aid in selecting targets with high barriers to drug resistance.

microbiology↗

bioRxiv2021

Defining the prototypical DNA replication fork trap in bacteria

In Escherichia coli, DNA replication termination is orchestrated by two clusters of Ter sites forming a DNA replication fork trap when bound by Tus proteins. The formation of a locked Tus-Ter complex is essential for halting incoming DNA replication forks. However, the absence of replication fork arrest at some Ter sites raised questions about their significance. In this study, we examined the genome-wide distribution of Tus and found that only the six innermost Ter sites (TerA-E and G) were significantly bound by Tus. We also found that a single ectopic insertion of TerB in its non-permissive orientation could not be achieved, advocating against a need for back-up Ter sites. Finally, examination of the genomes of a variety of Enterobacterales revealed a new replication fork trap architecture exclusively found outside the Enterobacteriaceae family. Taken together, our data enabled the delineation of a narrow prototypical Tus-dependent DNA replication fork trap consisting of only two Ter sites. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=198 HEIGHT=200 SRC="FIGDIR/small/453168v2_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@feb685org.highwire.dtl.DTLVardef@810368org.highwire.dtl.DTLVardef@6bed9org.highwire.dtl.DTLVardef@dbcff7_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗