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.
Abstract
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.
Glaesserella parasuis (G. parasuis, GPS) is a known causative agent of meningitis. A growing body of research indicates that non-coding RNAs (ncRNAs) are deeply involved in modulating inflammatory responses. In our study, we profiled the expression changes in circRNAs, lncRNAs, miRNAs, and mRNAs using a G. parasuis-induced mouse meningitis model and constructed the ceRNA networks by integrated analysis of the expression data. A total of 674 circRNAs, 376 lncRNAs, 57 miRNAs, and 373 mRNAs were differentially expressed. Functional GO and KEGG analysis showed enrichment of the source genes of differentially expressed (DE) circRNAs in protein binding, tight junction, and inflammatory pathways such as NF-kappaB, PI3K–Akt, and MAPK. The target genes of DEmiRNAs were enriched in phospholipase D, calcium, Rap1, and mTOR signaling pathways, whereas those of DElncRNAs were largely connected to tight junction, cytokine–cytokine receptor interaction, inflammatory response, and immune system processes. Subsequently, the DEcircRNAs–DEmiRNAs–DEmRNAs ceRNA network consisted of 177 DEcircRNAs, 20 DEmiRNAs, and 134 DEmRNAs, and the DElncRNAs–DEmiRNAs–DEmRNAs ceRNA network consisted of 152 DElncRNAs, 36 DEmiRNAs, and 177 DEmRNAs. Furthermore, the differential expression of randomly selected DEcircRNAs, DElncRNAs, DEmiRNAs, and DEmRNAs was confirmed by qRT-PCR, and the results were consistent with transcriptome sequencing. As far as we know, this study is the first integrative analysis for the ceRNA regulatory networks in G. parasuis-induced mouse meningitis, providing a theoretical basis for elucidating the pathogenic mechanisms of G. parasuis infection.
ABSTRACT African swine fever virus (ASFV) causes an incurable swine disease with nearly 100% mortality, posing a catastrophic threat to global pig production. The soft tick Ornithodoros lahorensis acts as a critical biological vector that sustains persistent ASFV replication and mediates long‐distance viral transmission, yet the molecular mechanisms governing ASFV‐tick interplay remain poorly understood. Here, we integrated transcriptomics and metabolomics to systematically dissect molecular changes in O. lahorensis across three infection stages: Uninfected control, early infection (7 days post‐infection, dpi), and late persistent infection (21 dpi). Multi‐omics integration revealed that ASFV extensively remodels tick host metabolism, predominantly activating purine/pyrimidine metabolism, lipid biosynthesis, and energy metabolism. We further characterized a conserved regulatory module consisting of 12 core genes and 8 signature metabolites that collectively support ASFV genome replication and virion assembly. Three hub metabolic genes (TK1, ATP5F1B, and IMPDH) were selected for functional validation via siRNA silencing in ticks; individual gene silencing suppressed ASFV loads by 89.2%, 91.5%, and 87.8%, respectively (p < 0.001***). This work represents the first comprehensive multi‐omics investigation of ASFV infection in O. lahorensis . We identified tick‐specific molecular targets to block vector‐mediated ASFV spread and established a standardized multi‐omics analytical pipeline for tick–virus interaction research. Our findings elucidate the mechanistic basis of long‐term ASFV persistence in soft ticks and deliver novel actionable clues for developing vector‐targeted ASF intervention strategies.
Jin Luo, Kai-Fei Guo, Fang Xiao et al.· The FASEB Journal· 0 citations
Findings provide the first functional evidence that CMPK2 restricts RGNNV infection in S. chuatsi, highlighting a conserved interferon-responsive antiviral module in teleost fish and identifying CMPK2 as a potential antiviral effector involved in host defense against RGNNV infection.
Chanxia Qin, Jinlong Huang, Linmiao Li et al.· Developmental and Comparativ...· 0 citations
Mactra veneriformis is an economically important bivalve mollusc in China, but its aquaculture is frequently threatened by Vibrio infections, particularly Vibrio alginolyticus. To investigate the molecular immune response of M. veneriformis to V. alginolyticus, we performed RNA-seq analysis of hepatopancreatic tissues collected at 48 h post-infection, the peak mortality time point, with PBS-injected individuals used as controls. Infection with V. alginolyticus caused severe histopathological damage in the hepatopancreas and resulted in a cumulative mortality of 53.3% over 14 d, compared with 3.3% in the control group. Transcriptomic analysis identified 2623 differentially expressed genes (DEGs), including 1585 significantly up-regulated genes and 1038 down-regulated genes. KEGG enrichment analysis demonstrated that DEGs were significantly enriched in immune related and metabolism pathways, including the JAK-STAT signaling pathway, RIG-I-like receptor (RLR) signaling pathway, and cytochrome P450 (CYP450) signaling pathway. Collectively, these findings revealed candidate immune related genes (tlr3, tlr5, myd88, nfkb1, il-17d, and ifi44l), a putative TLR-MyD88-NF-κB signaling axis, and KEGG signaling pathways, including JAK-STAT, RLR and CYP450, that may be involved in the innate immune response of M. veneriformis to V. alginolyticus infection. These results provide a transcriptomic basis for understanding host-pathogen interactions in this species and highlight candidate genes and pathways for future functional validation and potential application in disease-resistance breeding.
Hongda Li, Tao Liu, Qiang Li et al.· Comparative Biochemistry and...· 0 citations
High pathogenicity avian influenza (HPAI) poses a significant threat to poultry. Some chickens show resilience to HPAI, but the mechanisms involved are poorly understood. In this study, we aimed to identify the biological mechanisms associated with resilience to HPAIV infection in chickens. Chickens were inoculated with H7N1 HPAIV and classified as susceptible or resilient based on clinical signs, mortality, histopathological lesions, AIV antigen detection in tissues, and viral shedding. Blood transcriptomic analysis revealed that genes from resilient chickens are involved in the integrin-mediated signaling pathway (ITGA5, ITGA6, ITGB1), as well as in adaptive (BTK, TEC) and innate (TRIM13, LCK, TICAM1) immune pathways. Plasma proteomic profiling revealed that ARF4, EIF4A2, and HNRNPAB (proteins involved in fundamental cellular processes) were less abundant in resilient chickens compared to both controls and susceptible birds. Our results suggest that early modulation of these pathways is associated with resilience to HPAIV and likely reflects early viral control or reduced systemic dissemination rather than the absence of infection.
María J. Valdez-May, A. Perlas, M. Nofrarías et al.· Poultry Science· 0 citations
Photobacterium damselae subsp. piscicida (Pdp) is characterized by its broad distribution and is capable of infecting numerous cultured fish species. A previous study revealed the epidemic of Pdp in Lateolabrax maculatus with high mortality. In the current study, comparative transcriptome analysis was carried out on the spleens of L. maculatus infected with Pdp at 6, 12, and 24 hours post infection (hpi). The results demonstrated that compared with unchallenged individuals, Pdp infection resulted in 1631, 2085 and 2085 differentially expressed genes (DEGs) being detected at 6, 12 and 24 hpi, respectively. Among these, immune-related DEGs exhibited a trend of first increasing and then decreasing, particularly those involved in pattern recognition receptors, antigen processing and presentation, and inflammatory factors. In addition to terms related to immune system processes, GO enrichment analysis also identified terms related to signal transduction, metabolic processes, catalytic activity, and molecular function regulation. In KEGG enrichment analysis, numerous immune-related pathways were significantly enriched, such as the TNF signaling, NF-κB signaling, cytokine-cytokine receptor interaction, pattern recognition receptor, and natural killer cell mediated cytotoxicity. Subsequent weighted gene co-expression network analysis (WGCNA) uncovered immune-related pathways that were positively correlated at 6 and 12 hpi, and negatively correlated at 24 hpi, especially identified transcriptional trends suggesting Pdp may interfere with phagosome maturation and reduce endocytosis/autophagy-related gene expression at late infection stage. This study identified multiple immune-related genes and pathways that are dynamically regulated and potentially regulated by Pdp, which may contribute to its immune evasion and colonization in spotted sea bass. These findings provide new insights into the molecular immune mechanisms against Pdp infection and establish a basis for further studies on antibacterial defense in L. maculatus.
Jian Zhang, Dandan Zhou, Yan Gao et al.· Developmental and Comparativ...· 0 citations
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