Biology subjects

Villena-Gimenez, A.

Publications and source records attributed to Villena-Gimenez, A..

5 recordsLinked to original sources

bioRxiv2026

Simulated microgravity alters short-term evolutionary trajectories of Orsay virus in Caenorhabdidits elegans

BackgroundEnvironmental conditions shape the evolutionary trajectories of RNA viruses, yet little is known about how complex physical stressors such as microgravity influence host-virus interactions and viral evolution. Here, we investigated the short-term evolutionary consequences of simulated microgravity on the Caenorhabditis elegans - Orsay virus (OrV) system. MethodsOrV was subjected to six serial passages in hosts acclimated to low-shear modeled microgravity, with parallel evolution under standard-gravity. Evolutionary outcomes were evaluated using virulence, transmission, and replication traits, all measured under standard-gravity conditions. ResultsViral load fluctuated across passages in both environments, with lower mean accumulation in microgravity-evolved lineages. After evolution, we detected no significant changes in virulence. Transmission increased in standard-gravity lineages but not in microgravity-evolved ones, while viral replication decreased in all lineages, with a stronger decline in those evolved under microgravity. However, the magnitude of phenotypic changes was generally modest. DiscussionThese results indicate that evolution under microgravity can alter viral phenotypic trajectories over short timescales. However, because all traits were assayed under standard-gravity conditions, we cannot directly assess local adaptation to microgravity, and the observed differences may reflect environment-specific trade-offs rather than reduced fitness per se. Furthermore, the limited number of passages and the modest magnitude of phenotypic change suggest that evolutionary responses may still be in an early stage. ConclusionOverall, our findings provide initial evidence that simulated microgravity can influence the evolutionary dynamics of an RNA virus, while highlighting the need for reciprocal fitness assays and longer-term experiments to fully characterize adaptation to altered gravitational environments.

evolutionary biology↗

bioRxiv2026

Species-specific barriers constrict Orsay virus host range across the Caenorhabditis genus

Predicting the host range and spillover potential of RNA viruses requires understanding how ecological, immunological, and evolutionary factors jointly shape viral life cycles across related hosts. Here we integrate population-level viral load dynamics, single-animal heterogeneity, tissue-level progression, transmission competence, and evolutionary sustainability to map the eco evolutionary barriers that Orsay virus encounters across six Caenorhabditis species. We show that host species identity determines the timing and completeness of the viral life cycle, producing species specific combinations of susceptibility, replication kinetics, RNA2 to RNA1 stoichiometric balance, virion egress, and onward transmission. These phenotypes correspond to distinct host competence phenotypes, ranging from permissive (Caenorhabditis elegans) to restrictive or evolutionarily dead end host species. Alternative host species disrupt viral life cycle synchrony through delayed replication, truncated cycles, or failure to produce lumen localized virus, thereby reducing transmission and preventing viral adaptation upon serial passage. Our results demonstrate how temporal mismatches between viral replication and host physiology create a series of eco evolutionary barriers to emergence, offering a mechanistic framework for predicting viral host range.

evolutionary biology↗

bioRxiv2025

Cosmic silence and viral noise: transcriptomic crosstalk in Caenorhabditis elegans under simulated space conditions

Spaceflight environments pose unique physiological challenges due to altered gravity and radia-tion exposure. To investigate how these abiotic stressors interact with viral infection, we analyzed the transcriptomic response of Caenorhabditis elegans acclimated to simulated microgravity ({micro}G) and below-background muon radiation flux (BBR), upon infection with Orsay virus (OrV). Using RNA-seq, we characterized gene expression profiles across single and combined stress condi-tions. Both {micro}G and BBR elicited distinct stress responses, including modulation of oxidative stress, lipid metabolism, and immune pathways. OrV infection alone induced robust transcrip-tional changes, but its impact was significantly attenuated when combined with either abiotic stress, suggesting antagonistic interactions. Notably, proviral genes such as drl-1, fat-7 and hipr-1 were downregulated under BBR and {micro}G, potentially impairing viral replication. Gene ontology analyses revealed enrichment in immune effectors, RNA metabolism, and proteostasis-related pathways, particularly under BBR. Viral load and RNA2/RNA1 ratios were reduced in both stress conditions, indicating a shift in viral replication dynamics. Moreover, genomic diversity and de-fective viral genome formation were differentially affected, with increased genetic diversity and structural variation under stress. These findings suggest that acclimation to off-Earth conditions primes the host for a dampened response to an acute viral infection, potentially through resource reallocation and transcriptional attenuation. This study provides transcriptomic insight into viral infection under space-relevant conditions, highlighting complex stress interactions and their im-plications for host-pathogen dynamics in extraterrestrial environments.

microbiology↗

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

Microgravity and low muon radiation affect viral pathogenesis and physiology in Caenorhabditis elegans

Environmental conditions fundamentally shape host-pathogen interactions, yet how multiple extreme abiotic stressors combine to influence infection outcomes remains poorly understood. Organisms evolved under specific gravitational and radiation regimes; deviations from these conditions --whether in extreme terrestrial environments or beyond Earth-- may alter immune function and pathogen replication. In this study, we investigated the effects of reduced gravity and lowered muon flux on Orsay virus infection in the nematode Caenorhabditis elegans. We employed a fully factorial experimental design, examining how each factor, alone and in combination, influences physiological traits and viral load. While below-background radiation radically affected viral accumulation dynamics, reduced gravity had a minor effect. Both factors significantly impacted reproduction and morphology, with some effects magnified by viral infection. These results reveal how even partial modifications of Earth-like gravity and radiation levels can alter pathogen-host interactions. By integrating experimental observations with mathematical modeling, we show that these environmental stressors primarily affect prezygotic reproductive processes and modulate viral replication through distinct and sometimes antagonistic mechanisms. Although this work does not encompass the full complexity of space environments, where cosmic radiation includes high-energy protons and heavy ions, it provides insight into how adjustable models of reduced gravity and radiation can advance our understanding of biological adaptation beyond standard terrestrial conditions. IMPORTANCEUnderstanding how extreme environmental conditions affect host-pathogen interactions is critical both for safeguarding biological systems during spaceflight and for exploring fundamental principles of stress biology. This study demonstrates that reduced gravity and diminished muon radiation flux can significantly alter viral infection dynamics and host physiology in Caenorhabditis elegans. By integrating experimental data with mathematical modeling, we reveal that these abiotic stresses impact prezygotic reproductive processes and modulate viral replication in distinct and sometimes antagonistic ways. Our findings suggest that even partial deviations from Earth-like conditions can reshape infection outcomes and developmental trajectories, highlighting the need for deeper mechanistic insights into biological adaptation beyond terrestrial norms. These results have implications for space biosciences, evolutionary virology, radiation hormesis theory, and the design of countermeasures to preserve organismal health in extreme or non-terrestrial habitats.

microbiology↗