Identification and analysis of lncRNA50877, which is involved in KRT8-mediated mitochondrial homeostasis and GCRV replication in grass carp (Ctenopharyngodon idella).
Aug 2026· Developmental and Comparative Immunology· pp.
105718
· 0 citations· 50 references
Medicine
TL;DR
It is demonstrated that lncRNA50877 disrupts mitochondrial homeostasis by negatively regulating KRT8 expression, thereby modulating ROS levels, apoptosis, and autophagy; promoting oxidative stress-induced cell injury; and providing favorable conditions for GCRV replication.
Abstract
Grass carp (Ctenopharyngodon idella) reovirus (GCRV), the causative agent of hemorrhagic disease, causes substantial economic losses in the grass carp industry every year. However, the biological regulatory roles of long non-coding RNAs (lncRNAs) during GCRV infection remain largely unclear. In this study, high-throughput sequencing technology was used to analyze the expression profiles of lncRNAs in GCRV-infected and mock-infected liver and intestinal tissues of grass carp. In this study, compared with those in the control group, the transcriptomic profiles of grass carp after GCRV genotype II (HZ08 strain) infection revealed 742 upregulated and 1,259 downregulated lncRNA transcripts in the intestines, whereas 709 upregulated and 1,513 downregulated lncRNA transcripts were identified in the liver. GO and KEGG pathway analyses indicated that these lncRNAs were enriched primarily in pathways associated with biological process regulation, including "Pyruvate metabolism" and the "AMPK signaling pathway". Notably, we revealed that lncRNA50877 (PX600394) was upregulated in grass carp tissues and CIK cells following GCRV infection. CIK cells infected with equal titers of GCRV in vitro for 24 h exhibited aggravated cytopathic effect (CPE) upon lncRNA50877 overexpression. Furthermore, ChIRP-MS and RNA pull-down assays confirmed its direct interaction with KRT8 (keratin 8, PX531115). Our results demonstrated that lncRNA50877 disrupts mitochondrial homeostasis by negatively regulating KRT8 expression, thereby modulating ROS levels, apoptosis, and autophagy; promoting oxidative stress-induced cell injury; and providing favorable conditions for GCRV replication. In summary, lncRNA50877 may act as an autophagy-related lncRNA that regulates mitochondrial function and contributes to innate immune responses, offering new insights into the crosstalk between autophagy and innate immunity.
Findings suggest that NEAT1 and SNHG17, which have been reported to regulate inflammatory responses in multiple pathological conditions, may play important roles in the host response to L. donovani infection and could serve as potential targets for the prevention and treatment of leishmaniasis.
The molecular mechanism that CiATG13 mediates autophagy to regulate CiHSP70 expression and promote GCRV-I/II replication is revealed, the understanding of the interaction between fish viruses and autophagic molecules is enriched, and the potential strategy targeting CiATG13 for the prevention and control of GCHD is provided.
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Findings reveal temporally coordinated hepatic lipid metabolic reprogramming during GCRV-II infection and provide a foundation for further studies on how host lipid metabolism contributes to viral replication and pathogenesis.
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Overall, the findings indicate that lncRNAs exhibit origin-specific regulatory roles and are modulated by P. salmonis infection, highlighting their potential importance in fish immune responses.
Rodrigo Zuloaga, Luciano Ahumada-Langer, P. Dettleff et al.· Fishes· 0 citations
Simple Summary Cephalopholis sonnerati is an economically new aquaculture species in China. The red-spotted grouper nervous necrosis virus (RGNNV) exhibits high pathogenicity in larval C. sonnerati, but its immune response mechanisms remain unexplored, impeding the development of aquaculture. In the present study, we profiled brain transcriptome from healthy and naturally RGNNV-infected larvae. Many differentially expressed microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and fewer circular RNAs were identified. Enrichment analysis demonstrated that these targeted genes of differentially expressed ncRNAs were markedly enriched in innate immune defense, inflammatory, and cell death related pathways, such as JAK-STAT signaling pathway, NF-κB signaling pathway, apoptosis, and necroptosis. Furthermore, a lncRNA–miRNA–mRNA regulatory network focused on miR-93 was established, which may provide a valuable candidate target for future antiviral strategies in C. sonnerati. This study offers the first ncRNA transcriptome landscape of C. sonnerati during RGNNV infection, establishing a theoretical basis for elucidating host-RGNNV interaction mechanism in groupers.
Glaesserella parasuis (G. parasuis) is a major respiratory pathogen in piglets, but the regulatory mechanisms underlying its induced pulmonary inflammation remain poorly understood. In this study, whole-transcriptome sequencing was carried out on lung tissues from colostrum-deprived piglets with mild and severe serotype 5 G. parasuis infection and healthy controls. Differential expression (DE) analysis revealed 299 nominally DE mRNAs and 408 nominally DE lncRNAs in the mild group, increasing to 625 and 1193, respectively, in the severe group. Ingenuity Pathway Analysis identified the S100 family signaling pathway as a core inflammatory module predicted to be activated across both infection grades, with its transcriptional involvement expanding from 8 genes in mild infection to 42 genes in severe infection. Notably, G-protein-coupled receptors (GPCRs) accounted for nearly half (19/42) of the S100-associated DE genes in severe infection, covering multiple functional categories including chemokine receptors, lipid mediator receptors, and metabotropic receptors, suggesting systemic activation of the GPCR family in severe inflammation. Weighted gene co-expression network analysis identified multiple lncRNA candidates, among which two—LOC110256217 and LOC110259349—showed severity-associated connectivity patterns and were selected for further validation. Following G. parasuis infection, time-series RT-qPCR in 3D4/21 cells confirmed their co-expression with corresponding mRNAs and revealed distinct temporal patterns, suggesting their potential differential involvement at early and late stages of the inflammatory response. Collectively, these findings identify a putative lncRNA-S100-GPCR-associated inflammatory module linked to pulmonary inflammation in G. parasuis infection, providing a transcriptomic resource and candidate lncRNA-mRNA pairs for further functional studies and investigation into host resilience. Given the limited sample size (n = 3 per group), these findings should be considered exploratory and warrant validation in larger cohorts.
Jiayi Zeng, Xinqi Zeng, Xiangwei Deng et al.· Animals· 0 citations
