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ABSTRACT: Duck hepatitis A virus 1 (DHAV-1) is the primary cause of duck viral hepatitis, leading to sudden mortality in ducklings and significant economic losses in the duck industry. However, little is known about how DHAV-1 affects duckling liver at the molecular level. We conducted an analysis comparing the expression patterns of mRNAs and miRNAs in DHAV-1-infected duckling livers to understand the underlying mechanisms and dynamic changes. We identified 6,818 differentially expressed mRNAs (DEGs) and 144 differentially expressed microRNAs (DEMs) during DHAV-1 infection. Functional enrichment analysis of DEGs and miRNA target genes using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed their potential involvement in innate antiviral immunity, mitophagy, and pyroptosis. We constructed coexpression networks of mRNA-miRNA interactions and confirmed key DEMs (novel-mir333, novel-mir288, novel-mir197, and novel-mir71) using RT-qPCR. Further investigation demonstrated that DHAV-1 activates the RLRs signaling pathway, disrupts mitophagy, and induces pyroptosis. In conclusion, DHAV-1-induced antiviral immunity is closely linked to mitophagy, suggesting it could be a promising therapeutic target.

ABSTRACT: The cytokine storm induced by duck hepatitis A virus type 1 (DHAV-1) infection significantly contributes to severe, rapid deaths and economic losses in the duck industry in Egypt. This study aimed to investigate the potential inhibitory effect of a nanoemulsion containing turmeric and black pepper oil on the immune response and pathogenesis of DHAV-1 in ducklings. A total of 105 ducklings from nonvaccinated breeders were divided into 5 experimental groups, each comprising 21 birds. The negative control group (G1) remained noninfected with DHAV-1 and nontreated with nanoemulsion, while the positive control group (G2) was infected with DHAV-1 but not treated with nanoemulsion. The other 2 groups (G3, the supplemented group which was noninfected with DHAV-1), and group 4 (the prophylactic group G4) which was infected with DHAV-1, both received nanoemulsion throughout the experiment. Group 5 (G5, the therapeutic group), on the other hand, which was infected with DHAV-1 received nanoemulsion only from the onset of clinical signs. At 5 days old, the ducklings in the positive control (G2), the prophylactic (G4), and the therapeutic group (G5) were infected with DHAV-1. All the ducklings in the infected groups exhibited depression, anorexia, and opisthotonos, and their livers displayed various degrees of ecchymotic hemorrhage, liver enlargement, and microscopic pathological lesions. Notably, the positive control group (G2) experienced the most severe and pronounced effects compared to the other infected groups treated with the nanoemulsion. Meanwhile, the viral RNA loads were lower in the liver tissues of the infected ducklings treated with the nanoemulsion (G4, and G5) compared to the positive control group G2. Additionally, the nanoemulsion effectively modulated proinflammatory cytokine expression, antioxidant enzymes, liver enzymes, and lipid profile of treated ducklings. In conclusion, the turmeric and black pepper oil nanoemulsion has the potential to be a therapeutic agent for regulating and modulating the immune response, decreasing DHAV-1-induced cytokine storms, and minimizing mortality and economic losses in the duck business. More research is needed to understand how turmeric and black pepper oil nanoemulsion alleviates DHVA-1-induced cytokine storms and lowers duckling mortality.

ABSTRACT: Duck hepatitis A virus type 1 (DHAV-1) can cause severe liver damage in infected ducklings and is a fatal and contagious pathogen that endangers the Chinese duck industry. The objective of this study was to explore the correlation mechanism of liver metabolism-gut microbiota in DHAV-1 infection. Briefly, liquid chromatography-mass spectrometry and 16S rDNA sequencing combined with multivariate statistical analysis were used to evaluate the effects of DHAV-1 infection on liver metabolism, gut microbiota regulation, and other potential mechanisms in ducklings. In DHAV-1-infected ducklings at 72 h postinfection, changes were found in metabolites associated with key metabolic pathways such as lipid metabolism, sugar metabolism, and nucleotide metabolism, which participated in signaling networks and ultimately affecting the function of the liver. The abundance and composition of gut microbiota were also changed, and gut microbiota is significantly involved in lipid metabolism in the liver. The evident correlation between gut microbiota and liver metabolites indicates that DHAV-host gut microbiome interactions play important roles in the development of duck viral hepatitis (DVH).

Duck hepatitis A virus type 1 (DHAV-1) is the main pathogen of duck viral hepatitis, but the efficacy of the licensed commercial vaccine needs to be further improved. Therapeutic measures of specific drugs for DHAV-1-infected ducklings need to be urgently developed. Baicalin possesses good antiviral effects. This study aims to investigate the mechanism of baicalin in protecting hepatic mitochondrial function from DHAV-1. The ELISA method was used to detect changes of hepatic and mitochondrial catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX), inducible nitric oxide synthase (iNOS), adenosine triphosphate (ATP), and malondialdehyde (MDA) levels in vivo and vitro. Hematoxylin and eosin sections and transmission electron microscopy were used to observe liver pathological changes and mitochondrial structural changes. The changes in mitochondrial membrane potential were detected by JC-1 staining method. Western blot and quantitative real-time PCR were employed to analyze the gene and protein expressions in the nuclear erythroid 2-related factor 2 (Nrf2)/antioxidant responsive element (ARE) pathway in duck embryonic hepatocytes infected with DHAV-1. Results showed the administration of baicalin increased the survival rate of ducklings, and alleviated hepatic damage caused by DHAV-1 by enhancing the antioxidant enzyme activities of the liver and mitochondria, including SOD, GPX, CAT, and reducing lipid peroxidative damage (MDA content) and iNOS activities. The mitochondrial ultrastructure changed and the significant increase of ATP content showed that baicalin maintained the structural integrity and ameliorated mitochondrial dysfunction after DHAV-1 infection. In vitro, DHAV-1 infection led to loss of mitochondrial membrane potential and lipid peroxidation and decreased antioxidative enzyme activities (SOD, GPX) and mitochondrial respiratory chain complex activities (succinate dehydrogenase, cytochrome c oxidase). Baicalin relieved the above changes caused by DHAV-1 and activated the gene and protein expressions of Nrf2, which activated ARE-dependent genes including heme oxygenase-1 (HO-1), nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1 (NQO1), SOD-1, and GPX-1. In addition, baicalin increased the protein expressions of antioxidative enzymes (SOD, GPX). Hence, baicalin protects the liver against oxidative stress in hepatic mitochondria caused by DHAV-1 via activating the Nrf2/ARE signaling pathway.

Duck hepatitis A virus type 1 (DHAV-1) is a serious infectious virus of ducklings. Recent study showed baicalin (BA) and baicalin phospholipid complex (BAPC) possessed anti-DHAV-1 effect. However, the antiviral mechanism is not clear. Therefore, the aim of the present work is to study influences and mechanisms of BA and BAPC on DHAV-1. The effects of BA and BAPC on DHAV-1 replication were analyzed by CCK-8 and RT-qPCR methods. And the results showed BA inhibited the replication of DHAV-1, and BAPC was more effective. Then, the influences of BA and BAPC on DHAV-1 protein translation and RNA synthesis were detected by western blot and RT-qPCR. Both BA and BAPC inhibited the protein translation, and BAPC did better. Furthermore, BAPC also inhibited the RNA synthesis. Afterwards, DHAV-1 IRES activity, DHAV-1 3D protein stability, and cellular Hsp70 expression were studied to in-depth understand the inhibition effects of BA and BAPC on DHAV-1 replication. The results indicated BA and BAPC dropped the protein translation via suppressing DHAV-1 IRES activity. Additionally, BAPC dropped the RNA synthesis via reducing the 3D protein stability and inhibiting cellular Hsp70 expression. [ABSTRACT FROM AUTHOR]