Cyclic GMP-AMP (cGAMP) synthase (cGAS) is an intracellular sensor of cytoplasmic viral DNA created during virus infection, which subsequently activates the stimulator of interferon gene (STING)-dependent type I interferon response to eliminate pathogens. In contrast, viruses have developed different strategies to modulate this signalling pathway. Pseudorabies virus (PRV), an alphaherpesvirus, is the causative agent of Aujeszky’s disease (AD), a notable disease that causes substantial economic loss to the swine industry globally. Previous reports have shown that PRV infection induces cGAS-dependent IFN-β production, conversely hydrolysing cGAMP, a second messenger synthesized by cGAS, and attenuates PRV-induced IRF3 activation and IFN-β secretion. However, it is not clear whether PRV open reading frames (ORFs) modulate the cGAS–STING-IRF3 pathway. Here, 50 PRV ORFs were screened, showing that PRV UL13 serine/threonine kinase blocks the cGAS–STING-IRF3-, poly(I:C)- or VSV-mediated transcriptional activation of the IFN-β gene. Importantly, it was discovered that UL13 phosphorylates IRF3, and its kinase activity is indispensable for such an inhibitory effect. Moreover, UL13 does not affect IRF3 dimerization, nuclear translocation or association with CREB-binding protein (CBP) but attenuates the binding of IRF3 to the IRF3-responsive promoter. Consistent with this, it was discovered that UL13 inhibits the expression of multiple interferon-stimulated genes (ISGs) induced by cGAS–STING or poly(I:C). Finally, it was determined that PRV infection can activate IRF3 by recruiting it to the nucleus, and PRVΔUL13 mutants enhance the transactivation level of the IFN-β gene. Taken together, the data from the present study demonstrated that PRV UL13 inhibits cGAS–STING-mediated IFN-β production by phosphorylating IRF3.

Porcine epidemic diarrhea virus (PEDV) is a major causative pathogen of a highly contagious, acute enteric viral disease. This study evaluated the emergence of nine variants in Jiangsu and Anhui provinces of China from 2020 to 2023. S gene-based phylogenetic analysis indicated that three variants belong to the G1c subgroup, while the other six strains are clustered within the G2c subgroup. Recombination analyses supported that three variants of the G1c subgroup were likely derived from recombination of parental variants FR0012014 and a donor variant AJ1102. In addition, there are novel mutations on amino acid 141–148 and these likely resulted in changes in antigenicity in the three variants. These results illustrated that the study provides novel insights into the epidemiology, evolution, and transmission of PEDV in China.

Porcine epidemic diarrhea virus (PEDV), a highly infectious alphacoronavirus, has resulted in substantial economic losses within the global swine industry. Existing vaccines and therapeutic agents have proven inadequate in effectively preventing and controlling PEDV. Natural compounds offer distinct advantages in antiviral research due to their abundant availability, diverse biological activities, and low toxicity. In this study, the antiviral properties of the naturally occurring alkaloid 1-deoxynojirimycin (DNJ) against PEDV were examined. The CC₅₀ of DNJ was determined to be 912.5 μM through experimental analysis on Vero-E6 cells. DNJ demonstrated an inhibitory effect on PEDV activity, with a 50% inhibitory concentration (IC₅₀) of 57.76 μM. The compound primarily inhibited PEDV proliferation during the viral life cycle stages of attachment and replication. Moreover, DNJ mitigated the production of reactive oxygen species (ROS) and inflammation associated with PEDV infection. Computational docking predictions suggest that the viral non-structural proteins include Nsp12, Nsp14, and Nsp16 may serve as potential targets for DNJ. Consequently, DNJ represents a promising candidate for the development of novel therapeutic agents against PEDV.

Porcine epidemic diarrhea virus (PEDV) is the etiological agent responsible for the acute infectious intestinal disease known as porcine epidemic diarrhea (PED), which results in severe diarrhea in piglets and causes substantial economic losses to the global swine industry. Currently, no specific therapeutic agent is available for the clinical treatment of PEDV, highlighting the urgent need to screen antiviral compounds and investigate antiviral mechanisms to develop effective antiviral therapies. Using active natural ingredients in animal husbandry represents a significant contemporary trend. Natural herbal products offer numerous advantages, including abundant availability, diverse biological activities, and low toxicity and side effects, as well as a reduced likelihood of developing drug resistance. These attributes position them as valuable resources for the development of effective anti-PEDV drugs. This paper provides a comprehensive review of the current research on the inhibitory effects of herbal monomers (isolated compounds), single-herb extracts, and compound herbal formulations (derived from research) against PEDV. The aim is to establish a theoretical foundation for the screening and development of therapeutic and prophylactic agents targeting PEDV.

Oxidative stress (OS) significantly impairs poultry production; however, the protective mechanisms of rutin in the chicken liver remain unclear. In this study, we investigated the regulatory effects of rutin on oxidative stress and lipid metabolism using H₂O₂-exposed primary hepatocytes derived from chicken embryos. Specifically, we focused on antioxidant indicators, the Nrf2/Keap1 signaling pathway, and the ZAKα-mediated ribotoxic stress response (RSR). Results showed that pretreatment with 800 μmol/L rutin significantly alleviated oxidative damage by increasing superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activities, while decreasing malondialdehyde (MDA) and reactive oxygen species (ROS) levels. This protective effect was mediated by activation of the Nrf2/Keap1 signaling pathway and its downstream effectors, HO-1 and SOD2. Concurrently, rutin suppressed lipid accumulation, as evidenced by reduced levels of triglyceride (TG), total cholesterol (T-CHO), and low-density lipoprotein cholesterol (LDL-C), along with the downregulation of SREBP1 expression. Mechanistically, we found that rutin inhibited ZAKα and its downstream signaling, the p38/JNK pathway, which is associated with RSR. Crucially, co-treatment with ZAKα overexpression significantly attenuated the protective effects of rutin on both antioxidant defense and lipid regulation, confirming that rutin functions by inhibiting ZAKα-mediated signaling to restore Nrf2 activity. Molecular docking revealed a binding energy of −8.6 kcal/mol between rutin and ZAKα, verifying that ZAKα serves as a potential target for rutin. Collectively, these findings elucidate a novel mechanism whereby rutin enhances antioxidant defense and inhibits lipid deposition via the ZAKα-p38/JNK-Nrf2 signaling pathway, providing a theoretical basis for the application of rutin as a targeted regulator in poultry health.

Objective: Microtubule dynamics regulator protein 2 (RMDN2) plays a crucial role in cell division, cytoskeleton maintenance, and various cellular processes, thereby establishing it as a candidate gene influencing chicken follicle development in our previous studies. This research aims to explore single-nucleotide polymorphisms (SNPs), perform phylogenetic analysis, and assess sequence characteristics of RMDN2, offering valuable insights for molecular marker-assisted breeding and enhancing the understanding of its regulatory mechanisms.Methods: SNPs within the RMDN2 coding sequence region were identified in an F2 resource population. Bioinformatics tools were employed to investigate the effects of SNP mutations on the structure and function of RMDN2 protein. Additionally, a phylogenetic tree was constructed to elucidate the potential mechanisms underlying the role of RMDN2 in chicken laying traits.Results: Four novel exonic SNPs were identified: SNP1 (c.250G>A, p.Val84Ile), SNP2 (c.270G>C, p.Lys90Asn), SNP3 (c.533G>T, p.Gly178Val), and SNP4 (c.606G>A). The heterozygous genotypes of SNP1, SNP3, and SNP4 showed a significant association with increased egg number at 66 weeks (p<0.05). In contrast, the heterozygous genotype of SNP2 is associated with higher body weight at first egg (BWFE) (p<0.05). Notably, the H1H1 haplotype combination demonstrated a significant association with reduced BWFE, body weight at 105 days, and first egg weight (p<0.05). Missense mutations in SNP1, SNP2, and SNP3 may influence the hydrophilic/hydrophobic properties, transmembrane regions, functional domains, and secondary structure of the RMDN2 protein, potentially reducing its stability. Phylogenetic analysis demonstrated complete sequence homology between chicken and quail, indicating substantial conservation within species of the same order, while showing a marked decrease across different taxonomic orders.Conclusion: These findings enrich the candidate gene pool associated with the regulation of laying traits in chickens. However, further validation through in vivo and in vitro experiments remains necessary to strengthen the theoretical foundation for molecular breeding strategies.