Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2025.01.02.631049

Dissection of the Global Responses of Mandarin Fish Pyloric Caecum to An Acute Ranavirus (MRV) Infection Reveals the Formation of Serositis and Then Ascites

Zhang, W.·Li, Y.·Wu, X.·Sun, Q.·Fu, Y.·Weng, S.·He, J.·Dong, C.
View original source ↗Export metadata ↓

Abstract

Mandarin fish ranavirus (MRV), a variant of largemouth bass virus (LMBV), is a distinct member of the genus Ranavirus within the family Iridoviridae. Acute MRV infection predominantly affects the pyloric caecum, a critical visceral organ in mandarin fish, and is hypothesized to drive the characteristic external clinical sign of severe ascites. In this study, we reveal that acute MRV infection initially targets the serosal layer of the pyloric caecum of mandarin fish, leading to rapid progression into fibrinous serositis characterized by serosal hypertrophy, fibrosis, hyperemia, edema, and tissue adhesions. Using single-cell RNA sequencing, we dissect the cellular composition of epithelial, immune, and stromal populations, identifying significant enrichment of macrophages and granulocytes, alongside T and natural killer cells, as key mediators of acute cytokine and inflammatory responses. Then, robust experimental evidence demonstrates that MRV attacks specific immune cell subsets of T and B cells and stromal cells of fibroblasts, myofibroblasts, endothelial cells, and pericytes, resulting in upregulation of genes and pathways associated with extracellular matrix (ECM) formation, collagen biosynthesis, and vascular remodeling in the hyperplastic serosal zone. Additionally, both host-derived type V collagens and MRV-encoded collagens are implicated in ECM formation in the hypertrophic serosa. Collectively, this study provides a comprehensive single-cell resolution analysis of the pyloric caecums response to acute MRV infection and highlights virus- driven serositis as the underlying cause of severe ascites in mandarin fish. ImportanceThe pyloric caecum is a vital digestive and immune organ in many bony fish species, including the mandarin fish, a carnivorous species with an exceptionally developed pyloric caecum comprising 207-326 caeca per individual. While MRV/LMBV infects various fish species, severe ascites is uniquely observed in infected mandarin fish. This study demonstrates that acute MRV infection induces fibrinous serositis in the pyloric caecum, characterized by hyperemia, edema, and hyperplasia, ultimately resulting in ascites and mortality. Leveraging single-cell RNA sequencing, we provide a detailed landscape of the cell types affected or involved in the inflammatory response, revealing their roles in the pathogenesis of serositis. These findings advance our understanding of MRV-induced pathology and its species-specific manifestations.

Explore related subjects

microbiologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Zhang, W., Li, Y., Wu, X., Sun, Q., Fu, Y., Weng, S., He, J., Dong, C.. 2025-01-02. Dissection of the Global Responses of Mandarin Fish Pyloric Caecum to An Acute Ranavirus (MRV) Infection Reveals the Formation of Serositis and Then Ascites. https://doi.org/10.1101/2025.01.02.631049

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

KEEP EXPLORING

Related preprints

bioRxiv2026

A population-scale landscape of the subgingival microbiome reveals divergent routes to periodontal dysbiosis

Periodontitis is an archetypical mucosal inflammatory disease in which microbiome dysbiosis at the tooth-epithelial interface interacts with host genetic and behavioral risk factors to drive immune-mediated tissue destruction. Although subgingival microbiome compositional shifts are thought to parallel disease severity, microbiome variation at the population-level and its relationship to periodontal clinical phenotypes and disease-modifying factors remain poorly defined. Here, we use unsupervised manifold learning to map the compositional landscape of the subgingival microbiome in 1,355 adults spanning periodontal health to severe periodontitis. We identified eight latent microbiome states organized along a branching continuum from eubiosis to dysbiosis. An intermediate microbial configuration marked ecological destabilization and bifurcation into two distinct periodontitis-associated dysbiotic trajectories, distinguished by links to gingival inflammation and smoking. Although the microbiome trajectories broadly tracked periodontal destruction, a minority of individuals showed discordant microbiome-clinical phenotypes, with some individuals with periodontitis retaining otherwise eubiotic microbiomes enriched for low-abundance pathobionts, while some cases of health or mild disease had highly dysbiotic communities, suggesting distinct host susceptibility. Together, these findings define a population-scale ecological landscape of the subgingival microbiome, reveal divergent trajectories to periodontal dysbiosis, and highlight heterogeneity in the relationship between microbial community structure and clinical disease expression.

microbiology↗
bioRxiv2026

The iron-binding siderophore enterobactin is required for the response of multi-drug resistant Klebsiella pneumoniae to zinc limitation

To persist during infection Klebsiella pneumoniae must overcome nutrient iron and zinc limitation imposed by the host immune system through a process called nutritional immunity. Secreted small molecule siderophores are a major virulence determinant of Klebsiella pneumoniae pathogenesis and are presumed to overcome nutritional immunity by binding iron for bacterial acquisition. In this work, we set out to identify how a multi-drug resistant K. pneumoniae grows in zinc limited environments. Using unbiased transcriptomics, proteomics, and an arrayed transposon screen, we identified that synthesis and uptake of the siderophore enterobactin is required to allow for growth in low zinc conditions. Iron-specific chelators did not replicate this phenotype and addition of supplemental iron through heme in growth media could not complement severe growth defects of enterobactin mutant K. pneumoniae experiencing zinc limitation. Finally, zinc starvation induced enterobactin production independent of the canonical zinc uptake regulator (Zur) transcription factor suggesting an unidentified regulatory mechanism by which Gram-negative pathogens may respond to zinc stress. Together, these studies expand the role of enterobactin beyond iron regulation and highlight a previously unreported link between iron and zinc homeostasis in Klebsiella pneumoniae.

microbiology↗
bioRxiv2026

A microbiota-derived protease links phage susceptibility to host epithelial responses

Bacteriophages are major ecological drivers of gut microbial ecology, yet whether bacterial mechanisms that determine phage susceptibility have consequences for the mammalian host remains poorly understood. Here, we identify dipeptidyl peptidase 11 (Dpp11a), the predominant active serine protease of the prevalent gut commensal Phocaeicola vulgatus, as an unexpected bacterial defence factor. Dpp11a protects against environmental proteases and confers resistance to bacteriophage infection. Metatranscriptomic analyses further reveal increased expression of both dpp11a and P. vulgatus-associated phage transcripts in ulcerative colitis stool samples, indicating that both components of this interaction are transcriptionally active in disease-associated human microbiomes. Using the microfluidic gut-on-a-chip co-culture model HuMiX, we show that the absence of Dpp11 is accompanied by altered epithelial tight-junction remodelling during phage-bacterial infection. Together, our findings reveal that the consequences of bacterial phage defence can extend beyond phage-bacterium interactions to the mammalian epithelium.

microbiology↗