Project description:The pathogenesis of enteric viral infections arises from dual mechanisms: intrinsic viral replication dynamics and dysregulated host immune-inflammatory cascades. To bridge this knowledge gap, we developed macrophage-augmented intestinal organoids (MaugOs), a physiologically relevant model engineered by co-culturing primary human intestinal organoids with autologous macrophages. Using this platform, we interrogated five enteric viruses with distinct intestinal tropisms: Echovirus 1, Echovirus 6, Rotavirus, seasonal coronavirus OC43, and *SARS-CoV-2*. Key findings revealed that all tested viruses exhibited robust replication in MaugOs and activated canonical antiviral pathways (e.g., IFN-β/ISG15). Notably, Rotavirus, OC43, and *SARS-CoV-2* uniquely elicited inflammatory responses (IL-6/IL-8 upregulation), contrasting with the non-inflammatory phenotype of echoviruses. Mechanistically, acetate—a dominant gut microbial metabolite—dose-dependently attenuated virus-induced inflammation (NF-κB/STAT3 inhibition), while exhibiting cell-compartment-specific effects on viral replication: suppressing OC43 replication in macrophages but enhancing it in organoids. Furthermore, we established a combinatorial therapeutic strategy in MaugOs by pairing the antiviral agent nirmatrelvir with either anti-inflammatory drugs or acetate, achieving dual suppression of viral load (↓90%) and cytokine storm (IL-6/IL-8 ↓70%). These results position MaugOs as a transformative platform for 1) dissecting spatial virus-immune-epithelial interactions and 2) accelerating drug discovery targeting both viral pathogenesis and immunopathology.
2025-04-28 | GSE295767 | GEO
Project description:Phylodynamics of emerging echovirus 30 in Europe
Project description:Crassulacean acid metabolism (CAM) is a water-use efficient adaptation of photosynthesis that has evolved independently many times in diverse lineages of flowering plants. We hypothesize that convergent evolution of protein sequence and temporal gene expression underpins the independent emergences of CAM from C3 photosynthesis. To test this hypothesis, we generated a de novo genome assembly and genome-wide transcript expression data for Kalanchoe fedtschenkoi, an obligate CAM species within the core eudicots with a relatively small genome (~260 Mb). Our comparative analyses identified signatures of convergence in protein sequence and re-scheduling of diel transcript expression of genes involved in nocturnal CO2 fixation, stomatal movement, heat tolerance, circadian clock and carbohydrate metabolism in K. fedtschenkoi and other CAM species in comparison with non-CAM species. These findings provide new insights into molecular convergence and building blocks of CAM and will facilitate CAM-into-C3 photosynthesis engineering to enhance water-use efficiency in crops.
2018-01-09 | MTBLS519 | MetaboLights
Project description:Echovirus 30 from a large aseptic meningitis cluster
| PRJNA564342 | ENA
Project description:Direct diagnosis by near whole genome sequencing of Echovirus 12 meningitis, France