RESUMO
BACKGROUND: Fowl adenovirus-4 is a causative agent of hydropericardium hepatitis syndrome (HHS) in chickens and has been frequently reported from many countries. Fowl adenoviruses cause severe disease and mortality in broiler and layer breeders in Azerbaijan. Therefore, in this study, pathological lesions and the dissemination of fowl adenovirus-4 into the visceral organs of infected birds were investigated as well as molecular characterisation of detected strains. For this, liver, heart and spleen from 20 necropsied chickens originated from a broiler breeder flock and a layer breeder flock were embeded on the FTA cards and the samples were analysed for adenovirus-DNA by PCR and sequencing. RESULTS: The findings of necropsy in both broiler and layer breeder chickens were similar, and the liver was severely effected showing hepatitis, and the heart with hydropericardium lesions. The kidneys were swollen with haemorrhages and small white foci on the surface of the spleens were noted. Intestinal congestion and ecchymotic hemorrhages were also observed in some birds. Fowl adenovirus-4-DNA was detected by PCR in all collected organs of 20 birds. The sequence analysis revealed that fowl adenovirus-4 present in Azerbaijan and close similarity of the hexon genes of the adenoviruses existing in the Middle East, North America, far east and Indian subcontinent were determined by phylogenetic analysis. However, sequence diversity was detected from the adenovirus strains circulating in Europe, North and South America. CONCLUSIONS: This study indicates the impact of fowl adenovirus-4 on the poultry health and production, and improved disease control and prevention strategies are necessary to reduce the HHS disease in chickens in Azerbaijan.
Assuntos
Infecções por Adenoviridae , Galinhas , Filogenia , Doenças das Aves Domésticas , Animais , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/epidemiologia , Doenças das Aves Domésticas/patologia , Infecções por Adenoviridae/veterinária , Infecções por Adenoviridae/virologia , Infecções por Adenoviridae/epidemiologia , Azerbaijão/epidemiologia , Aviadenovirus/genética , Aviadenovirus/isolamento & purificação , Aviadenovirus/classificação , Hepatite Viral Animal/virologia , Hepatite Viral Animal/patologia , Hepatite Viral Animal/epidemiologia , DNA Viral/genética , Fígado/patologia , Fígado/virologia , Baço/patologia , Baço/virologiaRESUMO
Adenoviruses are a diverse group of viruses that can cause a variety of diseases in poultry, including respiratory and gastrointestinal infections. In turkeys (Meleagris gallopavo), adenoviruses commonly cause hemorrhagic enteritis and, rarely, inclusion body hepatitis. In this study, we investigated fowl adenoviruses (FAdVs) circulating in turkeys in Egypt. Following clinical examination of 500 birds, a portion of the hexon gene was amplified from four out of 50 samples from diseased birds (8%), and one amplicon that produced a strong band was selected for sequencing. Molecular and phylogenetic analysis revealed that the virus in that sample belonged to serotype FAdV-8b. Histopathological and immunohistochemical examinations of prepared tissue sections were performed to confirm the pathological findings. Diseased birds exhibited ruffled feathers, low body weight, a crouching posture, and diarrhea. Gross examination revealed petechial hemorrhage on the spleen, swollen pale liver, and congested intestine. Microscopic examination revealed the presence of eosinophilic and basophilic intranuclear inclusion bodies, nuclear pyknosis, and apoptotic bodies in the liver, congestion, hemorrhage, and fibrosis in the lungs, and desquamation of enterocytes. The presence of viral antigens in the liver, lungs, and intestine was confirmed by immunohistochemistry. To our knowledge, this is the first report of the characterization of an outbreak of inclusion body hepatitis in turkeys (hybrid converter breeds) due to FAdV-8b in Egypt. This finding raises an epidemiological alarm, necessitating further studies, including full-genome sequencing, to trace the virus's origin and genetic diversity.
Assuntos
Infecções por Adenoviridae , Aviadenovirus , Doenças das Aves Domésticas , Perus , Animais , Infecções por Adenoviridae/veterinária , Infecções por Adenoviridae/virologia , Infecções por Adenoviridae/patologia , Aviadenovirus/genética , Aviadenovirus/classificação , Aviadenovirus/isolamento & purificação , Proteínas do Capsídeo/genética , Egito , Hepatite Viral Animal/virologia , Hepatite Viral Animal/patologia , Corpos de Inclusão Viral/virologia , Fígado/virologia , Fígado/patologia , Filogenia , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/patologia , Perus/virologiaRESUMO
To determine the pathogenicity of two different genotypes of avian hepatitis E strains in two species of birds, a total of thirty healthy 12-week-old birds were used. After inoculation, fecal virus shedding, viremia, seroconversion, serum alanine aminotransferase (ALT) increases and liver lesions were evaluated. The results revealed that CHN-GS-aHEV and CaHEV could both infect Hy-Line hens and silkie fowls, respectively. Compared to the original avian HEV strain, the cross-infected virus exhibited a delay of 2 weeks and 1 week in emerged seroconversion, viremia, fecal virus shedding, and increased ALT level, and also showed mild liver lesions. These findings suggested that CHN-GS-aHEV may have circulated in chickens. Overall, these two different genotypes of avian HEV showed some variant pathogenicity in different bird species. This study provides valuable data for further analysis of the epidemic conditions of two avian HEVs in Hy-Line hens and silkie fowls.
Assuntos
Galinhas , Genótipo , Hepatite Viral Animal , Hepevirus , Doenças das Aves Domésticas , Eliminação de Partículas Virais , Animais , Galinhas/virologia , Doenças das Aves Domésticas/virologia , Hepevirus/genética , Hepevirus/patogenicidade , Hepevirus/isolamento & purificação , Hepevirus/classificação , Hepatite Viral Animal/virologia , Hepatite Viral Animal/patologia , Feminino , Fezes/virologia , Fígado/virologia , Fígado/patologia , Viremia/veterinária , Viremia/virologia , Infecções por Vírus de RNA/veterinária , Infecções por Vírus de RNA/virologia , Virulência , Alanina Transaminase/sangueRESUMO
Duck hepatitis A virus genotype 3 (DHAV-3) is the most popular pathogen of duck viral hepatitis (DVH) and has led to a huge economic threat to the Asian duck industry. In this work, we investigated the differences in the LC-MS/MS-based dynamic lipid profiles between susceptible and resistant Pekin duck lines with DHAV-3 infection. We found that the plasma lipidome of the two duck lines was characterized differently in expression levels of lipids during the infection, such as decreased levels of glycerolipids and increased levels of cholesteryl esters and glycerophospholipids in susceptible ducks compared with resistant ducks. By integrating lipidomics and transcriptomics analysis, we showed that the altered homeostasis of lipids was potentially regulated by a variety of differentially expressed genes including CHPT1, PI4K2A, and OSBP2 between the two duck lines, which could account for liver dysfunction, apoptosis, and illness upon DHAV-3 infection. Using the least absolute shrinkage and selection operator (LASSO) approach, we determined a total of 25 infection-related lipids that were able to distinguish between the infection states of susceptible and resistant ducks. This study provides molecular clues for elucidating the pathogenesis and therapeutic strategies of DHAV-3 infection in ducklings, which has implication for the development of resistance breeding.
Assuntos
Vírus da Hepatite do Pato , Hepatite Viral Animal , Infecções por Picornaviridae , Doenças das Aves Domésticas , Animais , Hepatite Viral Animal/patologia , Patos , Lipidômica , Cromatografia Líquida , Infecções por Picornaviridae/patologia , Doenças das Aves Domésticas/genética , Espectrometria de Massas em Tandem , Genótipo , LipídeosRESUMO
In order to ascertain the mechanism underlying the therapeutic efficacy of Bush sophora root polysaccharides (BSRPS) and phosphorylated Bush sophora root polysaccharides (pBSRPS) in the treatment of in duck viral hepatitis (DVH), an investigation was conducted to assess the protective impact of BSRPS and pBSRPS against duck hepatitis A virus type 1 (DHAV-1) induced mitochondrial dysfunction both in vivo and vitro. The BSRPS underwent modification through the utilization of the sodium trimetaphosphate - sodium tripolyphosphate method, and was subsequently characterized though Fourier infrared spectroscopy and scanning electron microscopy. Following this, the degree of mitochondrial oxidative damage and dysfunction was described through the use of fluorescence probes and various antioxidative enzyme assay kits. Furthermore, the utilization of transmission electron microscopy facilitated the observation of alterations in the mitochondrial ultrastructure within the liver tissue. Our findings demonstrated that both BSRPS and pBSRPS effectively mitigated mitochondrial oxidative stress and conserved mitochondrial functionality, as evidenced by heightened antioxidant enzyme activity, augmented ATP production, and stabilized mitochondrial membrane potential. Meanwhile, the histological and biochemical examinations revealed that the administration of BSRPS and pBSRPS resulted in a reduction of focal necrosis and infiltration of inflammatory cells, thereby mitigating liver injury. Additionally, both BSRPS and pBSRPS exhibited the ability to maintain liver mitochondrial membrane integrity and enhance the survival rate of ducklings infected with DHAV-1. Notably, pBSRPS demonstrated superior performance in all aspects of mitochondrial function compared to BSRPS. The findings indicated that maintaining mitochondrial homeostasis is a crucial factor in DHAV-1 infections, and the administration of BSRPS and pBSRPS may mitigate mitochondrial dysfunction and safeguard liver function.
Assuntos
Vírus da Hepatite do Pato , Hepatite Viral Animal , Hepatite Viral Humana , Infecções por Picornaviridae , Doenças das Aves Domésticas , Sophora , Animais , Hepatite Viral Animal/tratamento farmacológico , Hepatite Viral Animal/patologia , Patos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Sophora/química , Mitocôndrias , Polissacarídeos/química , Hepatite Viral Humana/tratamento farmacológico , Infecções por Picornaviridae/tratamento farmacológico , Infecções por Picornaviridae/patologia , Doenças das Aves Domésticas/tratamento farmacológicoRESUMO
BACKGROUND & AIMS: Fulminant viral hepatitis (FVH) is a life-threatening disease, but its pathogenesis is not fully understood. Neutrophil extracellular traps (NETs) were an unrecognized link between inflammation and coagulation, which are 2 main features of FVH. Here, we investigated the role and mechanism of NETs in the pathogenesis of FVH. METHODS: A mouse model of FVH was established by murine hepatitis virus strain-3 infection. Liver leukocytes of infected or uninfected mice were used for single-cell RNA sequencing and whole-transcriptome sequencing. NETs depletion was achieved using DNase 1. Acetaminophen was used to establish a mouse model of non-virus-caused acute liver failure. Clinically, NETs-related markers in liver, plasma, and peripheral neutrophils were assessed in patients with hepatitis B virus (HBV)-related acute liver injury. RESULTS: Increased hepatic NETs formation was observed in murine hepatitis virus strain-3-infected mice, but not in acetaminophen-treated mice. NETs depletion improved the liver damage and survival rate in FVH by inhibiting hepatic fibrin deposition and inflammation. An adoptive transfer experiment showed that neutrophil-specific fibrinogen-like protein 2 (FGL2) promoted NETs formation. FGL2 was found to directly interact with mucolipin 3, which regulated calcium influx and initiated autophagy, leading to NETs formation. Clinically, increased plasma NETs level was associated with coagulation dysfunction in patients with HBV acute liver injury. Colocalization of FGL2, NETs, and fibrin in liver was observed in these patients. CONCLUSIONS: NETs aggravated liver injury in FVH by promoting fibrin deposition and inflammation. NETs formation was regulated by the FGL2-mucolipin 3-autophagy axis. Targeting NETs may provide a new strategy for the treatment of FVH.
Assuntos
Armadilhas Extracelulares , Hepatite Viral Animal , Hepatite Viral Humana , Vírus da Hepatite Murina , Camundongos , Animais , Hepatite Viral Animal/metabolismo , Hepatite Viral Animal/patologia , Camundongos Endogâmicos BALB C , Acetaminofen/efeitos adversos , Cálcio/metabolismo , Vírus da Hepatite Murina/metabolismo , Fibrinogênio/genética , Fibrinogênio/metabolismo , Hepatite Viral Humana/complicações , Modelos Animais de Doenças , Inflamação , Autofagia , Fibrina/metabolismo , Desoxirribonucleases/metabolismoRESUMO
Theiler's disease (serum hepatitis) may occur in outbreaks or as single cases of acute hepatitis and is often associated with prior administration of equine-origin biologics approximately 4-10 weeks before the onset of clinical signs. Cases have also been described without any prior administration of blood products. The clinical disease has a low morbidity but high mortality and only adult horses are affected. The course of the disease is short, with horses either dying or completely recovering in a few days. Pathology in affected horses is predominantly centrilobular hepatocyte necrosis with mononuclear cell infiltration of the lesser affected periportal regions of the liver. Subclinical cases of the disease also occur. Based on the epidemiology and pathology of the disease, a viral cause, similar to hepatitis B in humans, has long been suspected. This paper reviews both historical and recent findings on Theiler's disease. Reported epidemics of Theiler's disease in the early 1900s are reviewed, along with their similarities to outbreaks of serum hepatitis in humans following yellow fever virus vaccinations in the 1930s and 1940s. Recent metagenomics-based studies to determine the aetiology of Theiler's disease are discussed, along with both clinical and experimental findings supporting equine parvovirus-hepatitis (EqPV-H) as the likely cause of this 100-year-old disease.
Assuntos
Hepatite Viral Animal , Hepatite , Doenças dos Cavalos , Infecções por Parvoviridae , Parvovirus , Animais , Hepatite Viral Animal/epidemiologia , Hepatite Viral Animal/patologia , Doenças dos Cavalos/epidemiologia , Doenças dos Cavalos/etiologia , Doenças dos Cavalos/patologia , Cavalos , Humanos , Infecções por Parvoviridae/veterináriaRESUMO
Several outbreaks of duck hepatitis A virus type 1 (DHAV-1), which were characterized by yellow coloration and hemorrhage in pancreatic tissues, have occurred in China. The causative agent is called pancreatitis-associated DHAV-1. The mechanisms involved in pancreatitis-associated DHAV-1 infection are still unclear. Transcriptome analysis of duck pancreas infected with classical-type DHAV-1 and pancreatitis-associated DHAV-1 was carried out. Deep sequencing with Illumina-Solexa resulted in a total of 53.9 Gb of clean data from the cDNA library of the pancreas, and a total of 29,597 unigenes with an average length of 993.43 bp were generated by de novo sequence assembly. The expression levels of D-3-phosphoglycerate dehydrogenase, phosphoserine aminotransferase, and phosphoserine phosphatase, which are involved in glycine, serine, and threonine metabolism pathways, were significantly downregulated in ducks infected with pancreatitis-associated DHAV-1 compared with those infected with classical-type DHAV-1. These findings provide information regarding differences in expression levels of metabolism-associated genes between ducks infected with pancreatitis-associated DHAV-1 and those infected with classical-type DHAV-1, indicating that intensive metabolism disorders may contribute to the different phenotypes of DHAV-1-infection.
Assuntos
Vírus da Hepatite do Pato/patogenicidade , Hepatite Viral Animal/virologia , Interações Hospedeiro-Patógeno/genética , Infecções por Picornaviridae/veterinária , Doenças das Aves Domésticas/virologia , Aminoácidos/genética , Aminoácidos/metabolismo , Animais , Patos/virologia , Expressão Gênica , Hepatite Viral Animal/genética , Hepatite Viral Animal/metabolismo , Hepatite Viral Animal/patologia , Pâncreas/citologia , Pâncreas/patologia , Pâncreas/virologia , Pancreatite/patologia , Pancreatite/virologia , Infecções por Picornaviridae/metabolismo , Infecções por Picornaviridae/patologia , Infecções por Picornaviridae/virologia , Doenças das Aves Domésticas/genética , Doenças das Aves Domésticas/metabolismo , Doenças das Aves Domésticas/patologia , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de RNARESUMO
Duck hepatitis A virus 3 (DHAV-3) is a wild endemic virus, which seriously endangers the duck industry in China. The present study aims to elucidate the mechanism of duck resistance to DHAV-3 infection. Both resistant and susceptible ducks were challenged with DHAV-3 in this experiment. The histopathological features and serum biochemical indices (ALT and AST) were analyzed to estimate liver injury status at 6, 12, 15, and 24 h post-infection (hpi). The dynamic transcriptomes of liver were analyzed to explain the molecular regulation mechanism in ducks against DHAV-3. The result showed that the liver injury in susceptible ducks was more serious than that in the resistant ducks throughout the four time points. A total of 2,127 differentially expressed genes (DEGs) were identified by comparing the transcriptome of the two populations. The expression levels of genes involved in innate immune response increased rapidly in susceptible ducks from 12 hpi. Similarly, the expression of genes involved in cytokine regulation also increased at the same time points, while the expression levels of these genes in resistant ducks remained similar between the various time points. KEGG enrichment analysis of the DEGs revealed that the genes involved in cytokine regulation and apoptosis were highly expressed in susceptible ducks than that in resistant ducks, suggesting that excessive cytokine storm and apoptosis may partially explain the mechanism of liver injury caused by DHAV-3 infection. Besides, we found that the FUT9 gene may contribute to resistance towards DHAV-3 in resistant ducklings. These findings will provide insight into duck resistance and susceptibility to DHAV-3 infection in the early phases, facilitate the development of a strategy for DHAV-3 prevention and treatment, and enhance genetic resistance via genetic selection in animal breeding.
Assuntos
Patos/genética , Vírus da Hepatite do Pato , Hepatite Viral Animal/genética , Infecções por Picornaviridae/genética , Doenças das Aves Domésticas/genética , Animais , Hepatite Viral Animal/patologia , Fígado/metabolismo , Fígado/patologia , Infecções por Picornaviridae/patologia , Infecções por Picornaviridae/veterinária , Doenças das Aves Domésticas/patologia , TranscriptomaRESUMO
Common marmosets infected with GB virus-B (GBV-B) chimeras containing hepatitis C virus (HCV) core and envelope proteins (CE1E2p7) developed more severe hepatitis than those infected with HCV envelope proteins (E1E2p7), suggesting that HCV core protein might be involved in the pathogenesis of viral hepatitis. The potential role of HCV core in hepatic inflammation was investigated. Six individual cDNA libraries of liver tissues from HCV CE1E2p7 or E1E2p7 chimera-infected marmosets (three animals per group) were constructed and sequenced. By differential expression gene analysis, 30 of 632 mRNA transcripts were correlated with the immune system process, which might be associated with hepatitis. A protein-protein interaction network was constituted by STRING database based on these 30 differentially expressed genes (DEGs), showing that IL-32 might play a central regulatory role in HCV core-related hepatitis. To investigate the effect of HCV core protein on IL-32 production, HCV core expressing and mock constructs were transfected into Huh7 cells. IL-32 mRNA and secretion protein were detected at significantly higher levels in cells expressing HCV core protein than in those without HCV core expression (P < 0.01 and P < 0.001, respectively). By KEGG enrichment analysis and using the specific signaling pathway inhibitor LY294002 for inhibition of PI3K, IL-32 expression was significantly reduced (P < 0.001). In conclusion, HCV core protein induces an increase of IL-32 expression via the PI3K pathway in hepatic cells, which played a major role in development of HCV-related severe hepatitis.
Assuntos
Callithrix , Hepatite Viral Animal/patologia , Inflamação , Interleucinas , Proteínas do Core Viral , Animais , Fosfatidilinositol 3-Quinases , Simplexvirus , Proteínas do Core Viral/genéticaRESUMO
Equine parvovirus-hepatitis (EqPV-H) has recently been associated with cases of Theiler's disease, a form of fulminant hepatic necrosis in horses. To assess whether EqPV-H is the cause of Theiler's disease, we first demonstrated hepatotropism by PCR on tissues from acutely infected horses. We then experimentally inoculated horses with EqPV-H and 8 of 10 horses developed hepatitis. One horse showed clinical signs of liver failure. The onset of hepatitis was temporally associated with seroconversion and a decline in viremia. Liver histology and in situ hybridization showed lymphocytic infiltrates and necrotic EqPV-H-infected hepatocytes. We next investigated potential modes of transmission. Iatrogenic transmission via allogeneic stem cell therapy for orthopedic injuries was previously suggested in a case series of Theiler's disease, and was demonstrated here for the first time. Vertical transmission and mechanical vectoring by horse fly bites could not be demonstrated in this study, potentially due to limited sample size. We found EqPV-H shedding in oral and nasal secretions, and in feces. Importantly, we could demonstrate EqPV-H transmission via oral inoculation with viremic serum. Together, our findings provide additional information that EqPV-H is the likely cause of Theiler's disease and that transmission of EqPV-H occurs via both iatrogenic and natural routes.
Assuntos
Hepatite Viral Animal/virologia , Doenças dos Cavalos/virologia , Fígado/virologia , Infecções por Parvoviridae/veterinária , Parvovirus/fisiologia , Animais , Dípteros/virologia , Fezes/virologia , Feminino , Hepatite Viral Animal/patologia , Hepatite Viral Animal/transmissão , Hepatócitos/patologia , Hepatócitos/virologia , Doenças dos Cavalos/patologia , Doenças dos Cavalos/transmissão , Cavalos , Transmissão Vertical de Doenças Infecciosas , Insetos Vetores/virologia , Fígado/patologia , Linfócitos , Masculino , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/virologia , Boca/virologia , Necrose , Infecções por Parvoviridae/patologia , Infecções por Parvoviridae/transmissão , Infecções por Parvoviridae/virologia , Parvovirus/isolamento & purificação , Parvovirus/patogenicidade , Tropismo Viral , Viremia , Eliminação de Partículas ViraisRESUMO
OBJECTIVE: The Fragile X mental retardation (FMR) syndrome is a frequently inherited intellectual disability caused by decreased or absent expression of the FMR protein (FMRP). Lack of FMRP is associated with neuronal degradation and cognitive dysfunction but its role outside the central nervous system is insufficiently studied. Here, we identify a role of FMRP in liver disease. DESIGN: Mice lacking Fmr1 gene expression were used to study the role of FMRP during tumour necrosis factor (TNF)-induced liver damage in disease model systems. Liver damage and mechanistic studies were performed using real-time PCR, Western Blot, staining of tissue sections and clinical chemistry. RESULTS: Fmr1null mice exhibited increased liver damage during virus-mediated hepatitis following infection with the lymphocytic choriomeningitis virus. Exposure to TNF resulted in severe liver damage due to increased hepatocyte cell death. Consistently, we found increased caspase-8 and caspase-3 activation following TNF stimulation. Furthermore, we demonstrate FMRP to be critically important for regulating key molecules in TNF receptor 1 (TNFR1)-dependent apoptosis and necroptosis including CYLD, c-FLIPS and JNK, which contribute to prolonged RIPK1 expression. Accordingly, the RIPK1 inhibitor Necrostatin-1s could reduce liver cell death and alleviate liver damage in Fmr1null mice following TNF exposure. Consistently, FMRP-deficient mice developed increased pathology during acute cholestasis following bile duct ligation, which coincided with increased hepatic expression of RIPK1, RIPK3 and phosphorylation of MLKL. CONCLUSIONS: We show that FMRP plays a central role in the inhibition of TNF-mediated cell death during infection and liver disease.
Assuntos
Proteína do X Frágil da Deficiência Intelectual/fisiologia , Hepatite Viral Animal/imunologia , Fator de Necrose Tumoral alfa/imunologia , Animais , Infecções por Arenaviridae/imunologia , Infecções por Arenaviridae/patologia , Linfócitos T CD8-Positivos/imunologia , Morte Celular/efeitos dos fármacos , Morte Celular/imunologia , Morte Celular/fisiologia , Células Cultivadas , Colestase/imunologia , Colestase/metabolismo , Colestase/patologia , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Hepatite Viral Animal/patologia , Hepatite Viral Animal/prevenção & controle , Hepatócitos/patologia , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Indóis/farmacologia , Indóis/uso terapêutico , Vírus da Coriomeningite Linfocítica , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína Serina-Treonina Quinases de Interação com Receptores/antagonistas & inibidores , Proteína Serina-Treonina Quinases de Interação com Receptores/fisiologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Formula Le-Cao-Shi (LCS) is a traditional Chinese medicine (TCM), which has long been used as a folk remedy against hepatitis B in China. The present study was conducted to evaluate the anti-hepatitis B effects of aqueous extract of LCS in vivo and in vitro. MATERIALS AND METHOD: we investigated the anti-HBV effects of LCS in vivo and in vitro with duck hepatitis B model and HepG2.2.15â¯cell line model, respectively. The serologic and cellular biomarkers and the histopathological changes were examined. RESULTS: By a duck hepatitis B model, the extract of LCS was found to restrain the expressions of duck hepatitis B surface antigen (DHBsAg), hepatitis B e antigen (DHBeAg), and HBV-DNA (DHBV-DNA). Moreover, LCS could decrease the levels of aspartate and alanine aminotransferases (AST and ALT) and ameliorate duck liver histological lesions. Correspondingly, in a HepG2.2.15 cellular model, LCS could also significantly inhibit the secretions of HBsAg and HBeAg. CONCLUSION: LCS exerted potent anti-hepatitis effects against the infection of HBV. The above results demonstrated the first-hand experimental evidences for the anti-hepatitis B efficiency of LCS. Our study provides a basis for further exploration and development of this promising compound prescription to treat hepatitis B disease.
Assuntos
Antivirais/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Hepatite B/tratamento farmacológico , Hepatite Viral Animal/tratamento farmacológico , Animais , Antivirais/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , DNA Viral , Patos , Hepatite B/imunologia , Hepatite B/patologia , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B do Pato/efeitos dos fármacos , Vírus da Hepatite B do Pato/genética , Vírus da Hepatite B do Pato/imunologia , Antígenos E da Hepatite B/imunologia , Hepatite Viral Animal/imunologia , Hepatite Viral Animal/patologia , Hepatite Viral Animal/virologia , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Medicina Tradicional ChinesaRESUMO
Duck hepatitis A virus (DHAV) is one of the pathogens that cause fatal duck viral hepatitis (DVH) in ducklings, which is an acute and contagious disease with a high mortality rate. Despite a continuing official duck vaccination program, DHAV infection remains a major threat to the duck industry. Considerable changes were observed in the epidemiology of DHAV-1/-3 in China over time. Therefore, comparing the pathogenicity of different DHAV serotypes can provide a theoretical basis for the diagnosis and prevention of DVH. In this study, we systematically investigated the effects of infection with DHAV-1/-3 field strains on clinical signs, gross lesions, histopathological changes, viral RNA detection, enzymatic systems, and metabolite concentrations. The results demonstrated that the major macroscopic and microscopic lesions in ducks infected with DHAV-1/-3 in the liver, brain, spleen, pancreas, and kidneys exhibited no significant differences. After 24 h of infection, DHAV quickly appeared in blood and major organs. Significant changes in clinical chemical markers together with histopathological lesions and viral RNA detection indicated that the liver is the major target organ for both viruses, resulting in impaired of liver integrity and function. In addition, we found that both viruses were able to invade both central and peripheral immune organs. Also lipase plasma activity was substantially affected by DHAV-1/-3, indicating that the integrity and function of the pancreas was compromised. However, there was no significant difference in pathogenicity between DHAV-1 and -3. The results of this study provide new insights into the pathogenesis of DHAV-1/3, two viruses that cause serious depression, metabolic disorders, and immunosuppression.
Assuntos
Patos , Vírus da Hepatite do Pato/fisiologia , Vírus da Hepatite do Pato/patogenicidade , Hepatite Viral Animal/virologia , Infecções por Picornaviridae/veterinária , Doenças das Aves Domésticas/virologia , Animais , Hepatite Viral Animal/patologia , Infecções por Picornaviridae/patologia , Infecções por Picornaviridae/virologia , RNA Viral/isolamento & purificação , VirulênciaRESUMO
BACKGROUND: Duck virus hepatitis (DVH) caused by duck hepatitis A virus type 1 (DHAV-1) is a malignant disease in ducklings, causing economic losses in the duck industry. However, there is still no antiviral drug against DHAV-1 in the clinic. OBJECTIVE: Our aim is to investigate the anti-DHAV-1 effect of baicalin, which is a flavonoid derived from the Chinese medicinal herb huangqin (Scutellaria baicalensis Georgi). METHODS: Here, we first detected its anti-DHAV-1 ability in vitro and in vivo. At the same time, the inhibition of baicalin on DHAV-1 reproduction was determined. Finally, we tested and verified the anti-oxidative and immuno-enhancing roles of baicalin on its curative effect on DVH. RESULTS: Baicalin possessed anti-DHAV-1 effect. It improved the cytoactive of DEH which was infected by DHAV-1 as well as reduced the DHAV-1 reproduction in DEH. Under baicalin treatment, mortality of ducklings infected by DHAV-1 decreased, additionally the DHAV-1 level and liver injury in such ducklings were significantly reduced or alleviated. The in vitro mechanism study indicated baicalin inhibited DHAV-1 reproduction via interfering the viral replication and release. Furthermore, the in vivo mechanism study manifested both the anti-oxidative and immuno-enhancing abilities of baicalin, which played crucial roles in its curative effect on DVH. CONCLUSION: This study may provide a scientific basis for developing baicalin as one or a part of the anti-DHAV-1 drugs.
Assuntos
Antivirais/farmacologia , Flavonoides/farmacologia , Vírus da Hepatite do Pato/efeitos dos fármacos , Hepatite Viral Animal/virologia , Animais , Antioxidantes/farmacologia , Células Cultivadas , Patos , Vírus da Hepatite do Pato/genética , Hepatite Viral Animal/tratamento farmacológico , Hepatite Viral Animal/mortalidade , Hepatite Viral Animal/patologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/virologia , Testes de Função Hepática , Extratos Vegetais , Scutellaria baicalensis , Liberação de Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacosRESUMO
Duck hepatitis A virus type 1 (DHAV-1) causes acute hepatitis with high morbidity and mortality in ducklings of the genera Cairina and Anas and is characterized by ecchymotic haemorrhage and necrosis of the liver surface. Since September 2011, a new subtype of DHAV-1 (named pancreatitis-type DHAV-1) has been isolated. This new subtype is characterized by yellowish or haemorrhagic pancreatitis, but with no significant pathological changes in the liver. To further investigate the difference in pathogenicity between hepatitis-type DHAV-1 and pancreatitis-type DHAV-1, we infected Muscovy ducklings with a hepatitis-type DHAV-1 strain, FZ86, or a pancreatitis-type DHAV-1 strain, MPZJ1206, and then compared the resulting gross lesions, histopathological changes, viral distribution and cellular apoptosis in the liver and pancreas of Muscovy ducklings. The results suggested that FZ86 induced a more efficient viral propagation in the liver than MPZJ1206, and the gross and histopathological lesions were also limited to the liver. However, MPZJ1206 induced more effective viral replication in the pancreas than FZ86. The MPZJ1206-infected Muscovy ducklings showed an obviously yellowed and haemorrhagic pancreas, but with no significant pathological changes in the liver. Furthermore, FZ86 induced notable hepatocyte apoptosis and increased the expression of caspase-3 in the liver, whereas MPZJ1206 caused apoptosis in a large number of acinar epithelial cells and elevated the expression of caspase-3 in the pancreas. Taken together, these results demonstrated that pancreatitis-type DHAV-1 has many new pathogenic features which distinguish it from the hepatitis-type DHAV-1. RESEARCH HIGHLIGHTS Pancreatitis-type DHAV-1 (MPZJ1206) was characterized by pancreatic haemorrhage and yellow discolouration, but with no obvious haemorrhage and necrosis in the liver. Pancreatitis-type DHAV-1 (MPZJ1206) exhibits many new pathogenic features which distinguish it from the hepatitis-type DHAV-1 (FZ86).
Assuntos
Patos , Vírus da Hepatite do Pato/patogenicidade , Hepatite Viral Animal/virologia , Pancreatite Necrosante Aguda/veterinária , Infecções por Picornaviridae/veterinária , Doenças das Aves Domésticas/virologia , Animais , Vírus da Hepatite do Pato/classificação , Hepatite Viral Animal/patologia , Fígado/patologia , Pâncreas/patologia , Pancreatite Necrosante Aguda/patologia , Pancreatite Necrosante Aguda/virologia , Infecções por Picornaviridae/patologia , Infecções por Picornaviridae/virologia , Doenças das Aves Domésticas/patologiaRESUMO
We previously showed that potassium channel tetramerization domain containing 9 (KCTD9) is aberrantly expressed in natural killer (NK) cells in patients with hepatitis B virus-associated acute-on-chronic liver failure and mice with experimental fulminant hepatitis. However, the mechanism underlying the regulation of NK cell function and fulminant hepatitis progression by KCTD9 is unknown. Here, we investigated the role of Kctd9 in regulation of early development, maturation, and function of NK cells using Kctd9-knockout mice. Compared to wild-type mice, Kctd9-deficient mice exhibited impaired NK cell lineage commitment, as evidenced by selective reduction in the refined NK progenitors, and incomplete NK cell maturation, as manifested by a higher proportion of CD11b- NK cells and a lower percentage of CD11b+ NK cells with high proliferative potential. Moreover, Kctd9-depleted NK cells displayed insufficient IFN-γ production, degranulation, and granzyme B production in response to cytokine stimulation, and attenuated cytotoxicity to tumor cells in vitro. The defect in NK cells was further supported by ameliorated liver damage and improved survival in Kctd9-deficient mice following murine hepatitis virus strain-3 (MHV-3) infection, which otherwise leads to immune-mediated fulminant hepatitis, a phenotype homologous to that caused by NK cell depletion in wild-type mice. Further investigation to identify the underlying mechanism revealed that Kctd9 deficiency hindered the expression of transcription factors, including Ets1, Nfil3, Eomes, and Id2 in NK cells. Collectively, our data reveal that Kctd9 acts as a novel regulator for NK cell commitment, maturation, and effector function.
Assuntos
Células Matadoras Naturais/metabolismo , Canais de Potássio/deficiência , Animais , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Proliferação de Células , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Regulação para Baixo , Hepatite Viral Animal/imunologia , Hepatite Viral Animal/patologia , Humanos , Células Matadoras Naturais/citologia , Células Matadoras Naturais/imunologia , Fígado/imunologia , Fígado/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Vírus da Hepatite Murina , Canais de Potássio/genética , Canais de Potássio/imunologia , Fatores de Transcrição/genética , Fatores de Transcrição/imunologiaRESUMO
Hydropericardium-hepatitis syndrome (HHS) is characterized by pericardial effusion and hepatitis and causes huge economic losses in the poultry industry in China. In this study, a strain of fowl adenoviruses (FAdV-4) (GX-1) was isolated from liver samples of diseased chickens with HHS. Phylogenetic analysis based on complete genome gene revealed that GX-1 clustered with the C-type fowl adenovirus and was serotyped as FAdV-4. Pathogenicity testing showed that the GX-1 strain caused 100% mortality in 10-day-old specific pathogen-free chickens at a dose of 104 tissue culture infective doses (TCID50) within 3 d post-infection. A viral dose of 103 TCID50 resulted in a 16% survival rate before day 9 and at 102 TCID50 an 80% rate before day 6. At necropsy, livers from infected chickens were swollen and yellow brown with necrotic foci. The hearts were flabby with amber-colored and jelly-like fluid in the pericardial sacs. The kidneys were swollen and congested. Histologically eosinophilic intranuclear inclusion body could be seen in the hepatic cell. The result of histopathological examination also revealed that heart muscle fibers were fractured with extensive congestion and hemorrhaging. Other tissues like kidney, bursa of Fabricius, thymus, and spleen were observed degeneration and necrosis. Virus-specific antibodies appeared in serum beginning at day 14 and reached statistically significant levels at 21, 28, 35, and 42 dpi (P < 0.001). In conclusion, we identified a highly virulent FAdV-4 virus as causative agent of the HHS outbreak reported here. The FAdV-4 GX-1 strain will be valuable for vaccine evaluation and development to prevent and reduce the spread of HHS in the poultry industry.
Assuntos
Infecções por Adenoviridae/veterinária , Aviadenovirus/isolamento & purificação , Derrame Pericárdico/veterinária , Doenças das Aves Domésticas/virologia , Infecções por Adenoviridae/patologia , Infecções por Adenoviridae/virologia , Animais , Aviadenovirus/genética , Galinhas , China , Hepatite Viral Animal/patologia , Hepatite Viral Animal/virologia , Derrame Pericárdico/virologia , Pericárdio , Sorogrupo , Organismos Livres de Patógenos Específicos , VirulênciaRESUMO
A 15-year-old female cockatiel (Nymphicus hollandicus) undergoing long term management for hepatopathy died and underwent necropsy. Microscopic findings were consistent with chronic liver disease characterized by distorted hepatic architecture, fibrosis and biliary proliferation. The additional finding of large intranuclear inclusion bodies within hepatocytes and renal tubular epithelium prompted diagnostic next generation sequencing. The assembled sequences isolated from pooled kidney and liver were related to siadenoviruses. The genus Siadenovirus, within the family Adenoviridae, includes several species of viruses that pathogenically infect avian species including hemorrhagic enteritis virus of turkeys and marble spleen virus of pheasants. Siadenoviruses have previously been reported in seven psittacine species: a plum-headed parakeet (Psittacula cyanocephala), an umbrella cockatoo (Cacatua alba) budgerigars (Melopsittacus undulates), an eastern rosella (Platycercus eximius), a scarlet chested parrot (Neophema splendida), a cockatiel (Nymphicus hollandicus), and a red-crowned parakeet (Cyanoramphus novaezelandiae). This report describes a novel siadenovirus in a cockatiel that is highly identical to budgerigar adenovirus 1 and distinct from PsAdV-2 in cockatiels. We report the clinical pathologic, gross, and histopathologic findings in a cockatiel with chronic hepatitis and a novel siadenovirus, PsAdV-5. The sequencing data is presented with a phylogenetic analysis.
Assuntos
Infecções por Adenoviridae/veterinária , Doenças das Aves/virologia , Cacatuas , Hepatite Viral Animal/virologia , Siadenovirus/classificação , Siadenovirus/isolamento & purificação , Infecções por Adenoviridae/virologia , Animais , Doenças das Aves/patologia , Feminino , Hepatite Viral Animal/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Histocitoquímica , Túbulos Renais/patologia , Túbulos Renais/virologia , Fígado/patologia , Fígado/virologia , Filogenia , Homologia de Sequência , Siadenovirus/genéticaRESUMO
BACKGROUND: A novel equine parvovirus (EqPV-H) was recently discovered in the equine liver with Theiler's disease. OBJECTIVES: To determine the prevalence of EqPV-H infection in naturally occurring Theiler's disease cases and in-contact horses in the absence of historical equine biologic product administration. ANIMALS: Ten cases of Theiler's disease from 6 separate properties were included in the study, based on the criteria of acute onset of clinical signs of liver failure with laboratory or histopathologic findings characteristic of Theiler's disease and no history of receiving an equine biologic product within the preceding 4 months. In addition, 37 in-contact horses from 4 of the 6 properties were screened for EqPV-H infection and hepatitis. METHODS: In prospective case series, cases were diagnosed with Theiler's disease by the attending veterinarian and were tested for EqPV-H by PCR of liver or serum. In-contact horses were assessed via serum chemistry and PCR at the attending veterinarian's discretion. Hepatitis was defined as serum gamma-glutamyltransferase activity above reference interval. The association of EqPV-H with hepatitis was determined by Fisher's exact test. RESULTS: Nine of 10 (90%) Theiler's disease cases and 54% of tested in-contact horses were EqPV-H positive. Hepatitis was significantly associated with EqPV-H infection (P = .036). CONCLUSIONS AND CLINICAL IMPORTANCE: Although further study is required to identify EqPV-H as the causative agent of Theiler's disease, EqPV-H appears strongly associated with cases of fatal Theiler's disease and subclinical hepatitis in horses in contact with those cases. The prevalence of EqPV-H infection on affected properties can be high.