bioRxiv Science⌕ Search

bioRxiv · 10.1101/2024.10.03.616447

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

Abstract

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.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Villena-Gimenez, A., Castiglioni, V. G., Legarda, E. G., Munoz-Sanchez, J. C., Gonzalez, R., Elena, S. F.. 2024-10-03. Microgravity and low muon radiation affect viral pathogenesis and physiology in Caenorhabditis elegans. https://doi.org/10.1101/2024.10.03.616447

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

A conserved cysteine-histidine-glutamate metal site identifies DUF501 (Rv1025), an essential uncharacterised protein family of Mycobacterium tuberculosis, as a candidate metalloenzyme and drug target

A substantial fraction of the Mycobacterium tuberculosis proteome remains functionally uncharacterised. Rv1025, a 155-residue protein carrying the domain of unknown function DUF501 (Pfam PF04417), is essential by transposon mutagenesis and vulnerable by CRISPR interference, an attractive but neglected drug target, yet has never been functionally described. The family (4,370 proteins, no Gene Ontology term, no solved structure) is uncharacterised across all organisms and essential in three Actinobacterial genera. A Foldseek search of the AlphaFold model against complete structural databases finds no significant homolog, indicating a novel fold. The operon eno-divIC-Rv1025-ppx2 is conserved across the Actinobacteria phylum, yet AlphaFold-Multimer finds no direct complex between Rv1025 and its neighbour DivIC. Instead, conservation across 8,700 homologous sequences reveals a near-invariant Cys113-His115-Glu59 cluster forming a pocket. Holo AlphaFold3 predictions with Zn, Fe and Mn confidently place a divalent metal on this triad at 2.25-2.47 A; mutating the triad relocates the metal, and an independent backbone-geometry predictor recovers the same site, confirming specificity. The triad is universal across the family: present in all 1,472 near-complete bacterial sequences of the Pfam alignment, with no non-conservative substitution among the 2,228 sequences examined, a defining feature of bacterial DUF501 rather than a mycobacterial peculiarity. We propose that DUF501 is a metal-binding protein and candidate metalloenzyme, the first functional hypothesis for this family, whose conserved, essential metal pocket is a promising drug target. As the predictions build on a conservation-defined site within a fully computational study, they are supportive rather than proof of metal occupancy and warrant experimental validation.

microbiology↗

Mycoplasmal endosymbionts of Trichomonas vaginalis are associated with reduced risk for Chlamydia trachomatis endometrial infection in asymptomatic, coinfected, women.

Trichomonas vaginalis is a protozoan parasite that causes trichomoniasis, the most common curable non-viral sexually transmitted infection, and Chlamydia trachomatis is a bacterial pathogen that can ascend to the upper genital tract and cause pelvic inflammatory disease, infertility, and ectopic pregnancy. T. vaginalis harbors bacterial endosymbionts, including Candidatus Malacoplasma girerdii, an obligate symbiont, and Metamycoplasma hominis, which can live freely or symbiotically. In a 16S rRNA sequencing study of the cervicovaginal microbiome of women at high risk for chlamydial infection, Ca. M. girerdii abundance was one of 13 features predicting lack of chlamydial spread to the endometrium, despite no direct association between T. vaginalis infection and reduced chlamydial ascension. Investigating the relationship between these microorganisms further, we found that T. vaginalis vaginal abundance correlated positively with chlamydial burden in women whose infection was confined to the cervix, while a nonsignificant inverse relationship was seen in women with endometrial spread. Among participants with high chlamydial burden, Ca. M. girerdii was detected exclusively in women without endometrial infection. Both endosymbionts trended toward more frequent detection, and higher abundance, in coinfected women without endometrial spread, while M. hominis abundance correlated strongly with T. vaginalis burden in this group. These findings suggest that mycoplasmal endosymbionts of T. vaginalis, rather than T. vaginalis itself, are microbial factors limiting chlamydial ascension, and point to a three-way interaction between parasite, endosymbiont, and bacterial pathogen that shapes upper genital tract C. trachomatis infection risk.

microbiology↗

Understanding the physiological alterations of Vibrio cholerae upon exposure to L-ascorbic acid

The scourge of cholera remains a major global public health threat. It affects up to 4 million people worldwide and causes tens of thousands of deaths each year. The disease is experiencing a concerning resurgence in many parts of Africa, the Middle East, and Asia. To effectively tackle cholera and circumvent rising antimicrobial resistance, targeted biological and preventive approaches, complementing traditional rehydration, are urgently needed. In this regard, our group has demonstrated the efficacy of L-ascorbic acid in controlling the growth and pathogenesis of Vibrio cholerae in vitro. The present work further provides a mechanistic elucidation of the L-ascorbic acid-mediated physiological changes in V. cholerae and also bolsters such a non-antibiotic approach to control cholera.

microbiology↗