ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Virology
Cosmic silence and viral noise: transcriptomic crosstalk in Caenorhabditis elegans under simulated space conditions
Provisionally accepted
Santiago F Elena1*
Ana Villena-Giménez1,2
Esmeralda G. Legarda1
Rubén González3Victoria G. Castiglioni1- 1I2SysBio, Spanish National Research Council (CSIC), Madrid, Spain
- 2I2SysBio, Consejo Superior de Investigaciones Cientificas, Madrid, Spain
- 3Institut Pasteur, Paris, France
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Spaceflight environments pose unique physiological challenges due to altered gravity and radiation exposure. To investigate how these abiotic stressors interact with viral infection, we analyzed the transcriptomic response of Caenorhabditis elegans acclimated to low shear modeled micro-gravity (LSMMG) and radiologically shielded environments (RSE), upon infection with Orsay virus (OrV). Using RNA-seq, we characterized gene expression profiles across single and combined stress conditions. Both LSMMG and RSE elicited distinct stress responses, including modulation of oxidative stress, lipid metabolism, and immune pathways. OrV infection alone induced robust transcriptional 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 RSE and LSMMG, potentially impairing viral replication. Gene ontology analyses revealed enrichment in immune effectors, RNA metabolism, and proteostasis-related pathways, particularly under RSE. Viral load and RNA2/RNA1 ratios were reduced in both stress conditions, indicating a shift in viral replication dynamics. Moreover, genomic diversity and defective viral genome formation were differentially affected, with increased genetic diversity and structural variation under stress. These findings suggest that acclimation to simulated off-Earth conditions primes the host for a dampened response to an acute viral infection, potentially through resource reallocation and transcriptional attenuation. This study pro-vides transcriptomic insight into viral infection under space-relevant conditions, highlighting complex stress interactions and their implications for host-pathogen dynamics in extraterrestrial environments.
Keywords: defective viral genomes, Gene Expression, host-pathogen interaction, microgravity, Orsay virus, radiologically shielded environments, stress response
Received: 05 Jan 2026; Accepted: 16 Feb 2026.
Copyright: © 2026 Elena, Villena-Giménez, Legarda, González and Castiglioni. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Santiago F Elena
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