Goose astrovirus 2 (GAstV-2) infection induces visceral gout in goslings, resulting in high mortality rates in birds aged 3–15 days. Despite extensive research since the virus was first identified in 2018, the innate immune defense mechanisms of the host against GAstV-2 remain incompletely characterized, impeding the development of effective vaccines and therapeutics. Here, we demonstrated that GAstV-2 infection upregulated Viperin expression both in vitro and in vivo, suggesting a potential role for Viperin as a host restriction factor. Further studies revealed that the P2 domain of viral ORF2 contributed to stimulate Viperin. Overexpression and knockdown experiments confirmed that Viperin exerts antiviral activity against GAstV-2. However, Viperin did not affect attachment or internalization. Mechanistic studies revealed that Viperin inhibits GAstV-2 by attenuating viral RNA-dependent RNA polymerase (RdRp) activity in a manner dependent on its S-adenosylmethionine (SAM) domain. The SAM domain was found to promote the production of 3'-deoxy-3',4'-didehydro-cytidine-5'-triphosphate (ddhCTP), which correlated with reduced RdRp activity and suppression of viral replication. Furthermore, intramuscular administration of ddhCTP reduced mortality and viral loads, and ameliorated GAstV-2-induced pathological injury in the kidney, spleen, and liver of goslings. Collectively, these findings identify Viperin as a key host restriction factor against GAstV-2 and highlight its potential as a target for antiviral strategies.

Despite long-term vaccination and control efforts, infectious bronchitis virus (IBV) remains a major threat to the global poultry industry, largely due to its high prevalence and extensive genetic diversity. This study aimed to characterize two novel GI-13 (4/91-like) IBV field strains, CK/CH/JS/2302 and CK/CH/AH/2307, isolated from H120-vaccinated broiler flocks in China, in order to elucidate their pathogenicity, genomic characteristics, and evolutionary relationships. Although both isolates belonged to the GI-13 genotype but exhibited divergent pathogenic profiles and evolutionary patterns. CK/CH/JS/2302 exhibited higher virulence, severe respiratory symptoms, tracheal hemorrhage, kidney lesions, and 10% mortality, while CK/CH/AH/2307 induced only mild respiratory signs and slight renal swelling. Phylogenetic analysis revealed that CK/CH/JS/2302 displayed a recombinant genome involving GX-YL5 and IBV/India/ck/01/23, in which the S1 gene was clustered within GI-13 genotype, whereas other genes showed high similarity to domestic GI-7, GI-19, and GI-22 genotypes. In contrast, CK/CH/AH/2307 showed high genomic similarity to the 4/91 vaccine strain without evidence of recombination but still impaired tracheal ciliary activity. Sequence and structural modeling of the S1 protein revealed that amino acid substitutions within hypervariable regions (HVRs) may affect receptor binding and antigenicity, potentially reducing cross-protection from current vaccines. These findings demonstrate the coexistence of a virulent recombinant strain (CK/CH/JS/2302) and a low-pathogenic variant (CK/CH/AH/2307) within the same lineage in China, underscoring the role of recombination and immune selection in IBV evolution. Overall, these findings emphasize the necessity for continuous molecular surveillance and genotype-specific vaccine development to improve protection against emerging 4/91-like IBV variants and reduce the economic losses caused by infectious bronchitis in poultry production.

Feline panleukopenia virus (FPV) is a highly contagious parvovirus that causes acute gastroenteritis, leukopenia, and high mortality in felids. Although domestic cats are commonly vaccinated, FPV continues to threaten captive and wild felids because of its environmental stability, rapid progression, and potential antigenic drift. In June 2022, a one-year-old captive female cougar (Puma concolor) at Hongshan Forest Zoo, Nanjing, China, was found dead following a peracute course without prodromal signs. The animal had previously received a trivalent feline vaccine containing feline panleukopenia, herpesvirus, and calicivirus antigens. Postmortem examination revealed perianal fecal staining, oral discharge, pulmonary congestion with peripheral emphysema, a darkened liver, and intestinal mucosal sloughing with petechiae. Histopathology revealed crypt epithelial necrosis, mucosal sloughing, and lymphoid depletion, which was consistent with parvoviral enteritis. Fecal and intestinal samples tested positive for FPV according to the lateral-flow assay and PCR. Viral replication was confirmed in CRFK cells via indirect immunofluorescence, and FPV antigen was shown to be localized to the intestinal crypt epithelium via immunohistochemistry. VP2 gene sequencing (1,753 bp) revealed that the isolate clustered with field strains from domestic cats in Jiangsu and Shanghai, which share near-complete nucleotide identity but differ from the Felocell vaccine strain in three amino acid substitutions (A91S, I232V, and L562V), two of which lie in antigenic loops and may affect antigenicity. No further FPV cases were detected during or after the 14-day observation period, reflecting successful containment through disinfection, relocation, feral cat control, and movement restrictions. This represents the first confirmed fatal FPV infection in a captive cougar in China and highlights the potential for local spillover from domestic reservoirs. The case underscores the need for continuous molecular surveillance, vaccination evaluation, and One Health–based biosecurity to protect susceptible wildlife populations at the human–domestic–wildlife interface.

Introduction:Enzootic nasal adenocarcinoma (ENA) is a nasal cancer that occurs in goats and sheep infected by enzootic nasal tumour virus. Pathologic examinations are useful for distinguishing tumours from inflammatory hyperplasia. The aim of this study was to describe the pathological characteristics of ENA. Material and Methods:Caprine tumour samples were collected for pathological examination. The tissue sections were stained with haematoxylin-eosin and periodic acid-Schiff (PAS) and processed for immunohistochemical staining. Tumour samples were also processed for routine transmission electron microscopy (TEM). Results:The histopathological structure of the tumours exhibited both papillary formations in the superficial regions and tubular or acinar formations in the deeper layers, representing distinct structural patterns within the same adenocarcinoma. The tumour cells were positive for PAS, and mitotic figures were rare. Low-differentiated cancer nests and epithelial-mesenchymal transition phenomena were observed. Immunohistochemical analysis showed that the tumour cells were strongly positive for pancytokeratin and cytokeratin (CK)18, moderately positive for CK7, and did not express olfactory marker protein. The Kiel 67 labelling index was approximately 23%. Retrovirus-like particles were distributed inside and outside of acinar tumour cells in TEM. Conclusion:The origin site of ENA is the epithelium of the nasal glandular tubules. This cancer is a low-grade adenocarcinoma with malignant potential. Cytokeratin 7 and CK18 can be considered immunophenotypes for identifying ENA tumour cells.

Goose astrovirus 2 (GAstV-2) infection leads to visceral gout and swollen kidneys in goslings, causing a 5–50% mortality rate and significant economic losses for goose flocks. While most studies on the virus’s pathological damage have focused on the kidneys, few reports have examined the effects of this fecal-oral pathogen on the digestive system. This study investigated GAstV-2 localization, cellular targets, and its impact on intestinal structure and homeostasis in orally infected goslings. Twenty 1-day-old goslings were randomly assigned to the infected and control groups. Clinical signs, organ lesions, viral distribution, histopathology, and alterations in intestinal cell populations, cytokine expression, and signaling pathways were assessed at 7 days post-infection. GAstV-2 was detected in the duodenum, jejunum, ileum, cecum, and rectum, with the highest viral load in duodenal crypt cells. Infection induced crypt cell necrosis, reduced villus height, decreased villus-to-crypt ratio, and lowered numbers of goblet cells and Lgr5+ intestinal stem cells. In contrast, Paneth cell abundance, Bmi1+ stem cells, and tight junction-related gene expression increased. Inhibition of stem cell differentiation into goblet cells was observed, mediated by modulation of the Notch signaling pathway. Proinflammatory cytokines, including IL-1β, IL-6, IL-8, IL-22, and TNF-α, were markedly upregulated, indicating a strong inflammatory response. These results demonstrate that GAstV-2 preferentially targets duodenal crypt cells, disrupts epithelial renewal, and impairs mucosal barrier function, while triggering compensatory regenerative and immune mechanisms. This study provides new insights into the intestinal pathogenesis of GAstV-2 and identifies potential targets for interventions to mitigate intestinal injury and economic losses in gosling production.

Goose astrovirus type 2 (GAstV-2) is a novel pathogen causing visceral gout in goslings; it not only causes necrosis of renal epithelial cells but also causes spleen damage, indicating that GAstV-2 induces immunosuppression in goslings. However, to date, the interaction between GAstV-2 and immune cells remains unclear. In this study, peripheral blood lymphocytes and macrophages were isolated from goslings without GAstV-2 infection and then inoculated in vitro with GAstV-2, and the virus localization in the lymphocytes and macrophages, proliferation and apoptosis of lymphocytes, and phagocytic activity, reactive oxygen species (ROS) and nitric oxide (NO) production, and cell polarity in macrophages were determined. The results showed that GAstV-2 was observed in the cytoplasm of CD4 and CD8 T cells and macrophages, indicating that GAstV-2 can infect both lymphocytes and macrophages. GAstV-2 infection reduced the lymphocyte proliferation induced by Concanavalin A and lipopolysaccharide stimulation and increased the lymphocyte apoptosis rate and mRNA expression of Fas, demonstrating that GAstV-2 causes damage to lymphocytes. Moreover, GAstV-2 infection enhanced phagocytic activity and production of ROS and NO and induced a proinflammatory phenotype in macrophages (M1 macrophages), indicating that macrophages play an antiviral role during GAstV-2 infection. In conclusion, these results demonstrate that GAstV-2 infection causes damages to lymphocytes, and host macrophages inhibit GAstV-2 invasion during infection.

Canine mammary tumor (CMT) is one of the relevant models of human breast cancer (HBC) with histopathological, epidemiological, and clinical characteristics similar to those of humans. This study aimed to establish and characterize a new canine cell line CMT-N7. CMT-N7 tumor is a complex canine mammary carcinoma that stained negative for human epidermal growth receptor-2 (HER2) and progesterone receptors (PR), and positive to estrogen receptor (ER). Cell growth, ultrastructure, doubling time, metastasis capacity, and biomarker characteristics of CMT-N7 were assessed. Xenograft transplantation was conducted to evaluate tumorigenicity. The cell morphology of CMT-N7 was generally epithelioid, with large and irregular nuclei and obvious multinucleation. The established CMT-N7 cell line underwent over 120 generations of subculture, exhibiting a rapid proliferation rate with a doubling time of 20.34h and a chromosome number ranging from 70 to 90. Transwell and wound healing assays demonstrated the CMT-N7 cells had invasive ability. Immunofluorescence analysis revealed positive expression of ER, alpha-SMA, CK-14, SOX-2, Vimentin, Ki-67, E-cadherin, and COX-2 in CMT-N7 cells. Following inoculation with CMT-N7 cells for two weeks, all mice developed tumors. Immunohistochemical analysis showed negative expression of HER-2 and PR, and positive expression of ER, Ki-67, E-cadherin, Vimentin, and COX-2. Consequently, the establishment of the canine mammary cancer cell line CMT-N7 provides a good model for investigating the mechanism of epithelial-mesenchymal transition (EMT) in both dogs and humans.

Goose astrovirus genotype 2 ( GAstV-2 ) mainly causes gout in goslings; therefore, it is a major pathogen threatening to goose flocks. However, the mechanisms underlying host-GAstV-2 interactions remain unclear because host cells suitable for GAstV-2 replication have been unavailable. We previously noted that GAstV2 is primarily located in goose renal epithelial cells, where it causes kidney damage. Therefore, here, we derived goose primary renal tubular epithelial ( RTE ) cells ( GRTE cells) from the kidneys of goose embryos after collagenase I digestion. After culture in Dulbecco 's modified Eagle medium/Nutrient mixture F-12 with 10% fetal bovine serum ( FBS ), the isolated cells had polygonal with roadstone-like morphology; they were identi fied to be epithelial cells based on the presence of cytokeratin 18 expression detected through immuno fluorescence assay ( IFA ). GAstV-2 infection in GRTE cells led to no obvious cytopathic effects; the maximum amounts of infectious virions were observed 48 h post infection through IFA and quantitative PCR. Next, RNA-seq was performed to identify and map post - GAstV-2 infection differentially expressed genes. The downregulated pathways were mainly related to metabolism, including tryptophan metabolism, drug metabolism by cytochrome P450, xenobiotic metabolism by cytochrome P450, retinol metabolism, butanoate metabolism, starch and sucrose metabolism, ascorbate and aldarate metabolism, and drug metabolism by other enzymes and peroxisome. In contrast, the upregulated pathways were mostly related to the host cell defense and proliferation, including extracellular matrix - receptor interaction, complement and coagulation cascades, phagosome, PI3K-Akt signaling pathway, human T-lymphotropic virus 1 infection, lysosome, and tumor necrosis factor signaling pathway. In conclusion, we developed a GRTE cell line for GAstV-2 replication and analyzed the potential host - GAstV-2 interactions through RNA-seq; our results may aid in further investigating the pathogenic mechanisms underlying GAstV-2 infection and provide strategies for its prevention and control.

Goose astrovirus (GAstV)-2, a novel pathogen identified in 2018, mainly causes visceral gout in goslings, leading to approximately 50% mortality. At present, no commercial veterinary products are available to prevent and treat the disease. Our previous studies showed that nitric oxide (NO) and inducible NO synthase (iNOS) were markedly higher in the kidney and spleen of goslings infected with GAstV-2, but their effects during GAstV-2 infection remain unclear. In the present study, goslings were intraperitoneally injected with aminoguanidine (AG)-an iNOS inhibitor-to examine the role of NO during GAstV-2 infection. AG significantly decreased the serum NO concentration and iNOS mRNA expression in the kidney. Moreover, AG reduced the mortality, serum uric acid and creatinine content, and urate deposition in visceral organs and joints. Histopathological analysis demonstrated that AG reduced renal tubular cell necrosis, inflammatory cell infiltration, glycogen deposition in glomerular mesangium, and interstitial fibrosis, suggesting alleviation of kidney lesions. Furthermore, AG decreased the expression of renal injury markers such as KIM-1 and desmin; inflammatory cytokine-related genes such as IL-1β, IL-8, and MMP-9; and autophagy-related genes and proteins such as LC3II, ATG5, and Beclin1. However, quantitative real-time PCR and immunohistochemistry showed that treatment with AG did not affect the kidney and liver viral load. These findings suggest that AG decreases the mortality rate and kidney lesions in goslings infected with GAstV-2 through mechanisms associated with autophagy and inhibition of inflammatory cytokine production in the kidney but not with GAstV-2 replication.

N6-methyladenosine (m6A), the most common modification in mammalian mRNA and viral RNA, regulates mRNA structure, stability, translation, and nuclear export. The Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus causing severe neurologic disease in humans. To date, the role of m6A modification in JEV infection remains unclear. Herein, we aimed to determine the impact of m6A methylation modification on JEV replication in vitro and in vivo. Our results demonstrated that the overexpression of the m6A reader protein YTHDF1 in vitro significantly inhibits JEV proliferation. Additionally, YTHDF1 negatively regulates JEV proliferation in YTHDF1 knockdown cells and YTHDF1 knockout mice. MeRIP-seq analysis indicated that YTHDF1 interacts with several interferon-stimulated genes (ISGs), especially in IFIT3. Overall, our data showed that YTHDF1 played a vital role in inhibiting JEV replication. These findings bring novel insights into the specific mechanisms involved in the innate immune response to infection with JEV. They can be used in the development of novel therapeutics for controlling JEV infection.

The aim of this study was to describe radiography, computed tomography (CT), and magnetic resonance imaging (MRI) findings of enzootic nasal tumors in goats infected with enzootic nasal tumor viruses. Five of six goats with a mean age of 2 years, showed clinical signs of respiratory disease. Head radiographs showed increased density of the unilateral or bilateral nasal cavity in four goats, and a CT scan showed that the space-occupying lesion of the nasal cavity originated from the ethmoid bone and was enhanced homogeneously postcontrast in all goats. The nasal concha was destroyed and the paranasal sinus mucosa was thickened and filled with fluid in some goats. On MRI, the mass exhibited equal or slightly higher signal intensity on T2 weighted images, equal signal intensity on T1 weighted images, a high signal on fluid-attenuated inversion recovery images and heterogeneous enhancement postcontrast. After dissection, histopathological examination of the mass and virus genome detection of the nasal secretions confirmed that the intranasal mass was a low-grade adenocarcinoma and that the goats were infected with enzootic nasal tumor virus type 2. In conclusion, CT and MRI have high diagnostic values for enzootic nasal tumors because they match the postmortem findings and are more accurate than radiography.

Goose astrovirus (GAstV) is a novel pathogen that was discovered in 2018. It has two genotypes, GAstV-1 and GAstV-2, and both can cause visceral gout of goslings and result in significant economic losses. The present work aimed to develop a duplex TaqMan real-time quantitative reverse transcription PCR (RT-qPCR) assay to distinguish the two genotypes. MegAlign software was used to design two pairs of primers and a pair of matched probes based on the open reading frame 2 (ORF2) sequence with the greatest difference between GAstV-1 and GAstV-2, and primer and probe concentrations and annealing temperatures were optimised. Fluorescence signals were obtained for GAstV-1 and GAstV-2 in the FAM and VIC channels, respectively, but no fluorescent signal was observed for other pathogens. The detection limit for GAstV-1 and GAstV-2 was 33.3 and 33.7 DNA copies/μL, respectively. Intra- and inter-assay variability tests revealed excellent reproducibility. Furthermore, the assay detected GAstV-1 and GAstV-2 in allantoic fluids (100% positive) spiked with viruses, and 70 clinical gout gosling samples were examined, of which 11.4% were positive for GAstV-1, 74.3% were positive for GAstV-2%, and 5.7% were positive for mixed infection. In summary, the developed duplex RT-qPCR assay has high specificity, sensitivity, and reproducibility, and can be used in the clinic for detection of GAstV-1 and GAstV-2.

Goose nephritic astrovirus (GNAstV) was first isolated in 2018, causing great economic losses to the goose industry. However, little is known about host immune response to GNAstV infection. In this study, forty 2-day-old goslings were randomly divided into 2 groups: infection and negative control groups. Each gosling in the infection group was challenged with 0.5 mL GNAstV-JSHA intramuscularly, whereas the gosling in the negative control group was inoculated with the same amount of PBS. Histopathological changes and virus location in the spleen and kidney were examined, and the expression of immune-related genes was determined by qPCR at 7 and 14 d after infection. Our results showed that GNAstV infection induced degeneration and necrosis of splenic lymphocytes and renal epithelial cells, and these cells were positive for the virus. In addition, GNAstV infection induced the activation of pattern recognition receptors (RIG-I, MDA-5, and TLR3) and key adaptor molecules (MyD88, MAVS, and IRF7) in the spleen and kidney, and upregulated the gene expression of interferon-α in the spleen and antiviral proteins (MX1, OASL, and IFITM3) in the spleen and kidney. Moreover, high expression levels of interleukin (IL)-1β and IL-8 in the spleen and iNOS in the spleen and kidney were found. These results indicated that GNAstV infection activated host innate immune response. Furthermore, GNAstV infection increased the expression levels of CD8+, MHCI, and MHCII, indicating that adaptive immune response was activated. Besides, TGF-β was highly expressed in the spleen and kidney, which may be an immune evasion strategy of GNAstV to cause infection. Interestingly, both IL-1β and IL-6 mRNA levels were decreased in the kidney, which may help reduce kidney lesions. This is the first study to report changes in immune-related gene expression in response to GNAstV infection, and our results provide insights into viral pathogenesis.

Goose nephritic astrovirus (GNAstV) has recently been identified, which causes kidney swelling and visceral gout in goslings. However, the pathological changes in kidney tissue due to GNAstV infection have not yet been described. In the study, fifty goslings were orally infected with GNAstV, and fifty goslings received PBS as a control. Kidney tissue was collected at different days following infection (dpi) to assess the injury. GNAstV infection reduced body weight, increased the relative weight of the kidney, and increased serum uric acid and creatinine levels. GNAstV was found within renal epithelial cells, and the viral load in the kidney peaked at 7 dpi. Pale and swollen kidney tissue was observed in infected goslings, especially at 5 and 7 dpi. GNAstV infection caused degeneration and necrosis of renal epithelial cells, structural destruction of the brush border, glycogen deposition in the glomerular mesangium, increased fibrosis, and infiltration of inflammatory cells into the renal interstitium. Moreover, swollen mitochondria, broken mitochondrial ridges, autophagosomes, and autophagolysosomes were observed under ultrahistopathological examination. GNAstV infection increased levels of LC3B, ATG5, and Beclin 1, and decreased p62, and downregulated WT1 mRNA and upregulated desmin mRNA. At early stages, GNAstV infection decreased expression of intercellular junction-related genes, including ZO-1, occludin, claudin-10, and catenin-α2. In conclusion, GNAstV infection causes renal epithelial cell autophagy, destruction of brush border and intercellular junctions, podocyte damage, and increased fibrosis, ultimately resulting in damage to the kidney.

Cyclic GMP-AMP synthase (cGAS) is a main sensor used to detect microbial DNA in the cytoplasm, which subsequently induces the production of interferon (IFN) via the cGAS/STING/IRF3 signaling pathway, leading to an antiviral response. However, some viruses have evolved multiple strategies to escape this process. Pseudorabies virus (PRV) is a double-stranded DNA virus belonging to the Alphaherpesvirinae subfamily, which can cause serious damage to the porcine industry. Many herpesvirus components have been reported to counteract IFN production, whereas little is known of PRV. In the present study, we found that PRV glycoprotein E (gE) was involved in counteracting cGAS/STING-mediated IFN production. Ectopic expression of gE decreased cGAS/STING-mediated IFN-β promoter activity and the level of mRNA expression. Moreover, gE targeted at or downstream of IRF3 was found to inhibit IFN-β production. However, gE did not affect the phosphorylation, dimerization and nuclear translocation of IRF3. Furthermore, gE is located on the nuclear membrane and could subsequently degrade CREB-binding protein (CBP). MG132, a proteasome inhibitor, decreased CBP degradation and restored the IFN-β production induced by gE. Finally, gE-deleted PRV induced a higher level of IFN-β production and reduced CBP degradation compared to wild-type PRV. Together, these results demonstrate that PRV gE can inhibit cGAS/STING-mediated IFN-β production by degrading CBP to interrupt the enhanced assembly of IRF3 and CBP.

The emergence of a novel goose nephritic astrovirus (GNAstV) has caused economic losses to the Chinese goose industry. High viral load is found in the spleen of goslings infected with GNAstV, but pathological injuries to the spleen due to GNAstV are largely unknown. In this study, 50 two-day-old goslings were infected orally with GNAstV, and 50 goslings were treated with PBS as control. Spleens were collected at different times following infection to assess damage. GNAstV infection caused visceral gout and urate deposition in joints, and resulted in 16% mortality. GNAstV was found in the lymphocytes and macrophages within the spleen. Lymphocyte loss, especially around the white pulp, and destruction and decline in the number of reticular fibers was observed in GNAstV-infected goslings. Moreover, in GNAstV-infected goslings, ultrahistopathological examination found that splenic lymphocytes exhibited condensed chromatin and apoptotic bodies, and reticular cells displayed damage to plasma membrane integrity and swollen mitochondria. Furthermore, TUNEL staining confirmed apoptosis of lymphocytes, and the mRNA levels of Fas and FasL were significantly increased in the GNAstV-infected goslings. In addition, GNAstV infection reduced the number and protein expression of CD8. In conclusion, GNAstV infection causes lymphocyte depletion, reticular cell necrosis, reticular fiber destruction, lymphocyte apoptosis, and reduction in CD8 levels, which contribute to spleen injury.

In 2018, a new goose astrovirus (GAstrV) was reported in China, which causes 2 to 20% deaths in 4- to 16-day-old goslings causing great damages to the livestock industry. Gout is the typical feature of GAstrV infection in goslings. However, the mechanism of gout formation remains unclear. In the present study, 2-day-old goslings were infected intramuscularly with GAstrV for 14 D. One quarter of the infected goslings died, and typical gout pathological changes were found in the dead infected goslings. Pathological changes were observed in the morphology of the kidney and liver, such as degeneration, necrosis, and inflammatory cell infiltration. Accordingly, a high virus load was found in both organs. The serum level of uric acid in the inoculated goslings was higher, whereas no differences were found in levels of creatinine, calcium, and phosphorus. Moreover, the xanthine dehydrogenase (XOD) and adenosine deaminase (ADA) activities and the mRNA levels of xanthine dehydrogenase, adenosine deaminase, phosphoribosyl pyrophosphate amidotransferase, and phosphoribosyl pyrophosphate synthetase 1 in livers increased, wheres the multidrug resistance–associated protein 4 mRNA level and Na-K-ATPase activity in the kidneys decreased. These results showed that GAstrV infection could cause lesions on the liver and kidney and then increase the expression or activity of enzymes related to uric acid production in the liver and decrease renal excretion function, which contribute to hyperuricemia and gout formation.

Entering the nucleus is important for Porcine circovirus type 2 (PCV2) replication. Karyopherins (KPNs) mediate the nuclear import of many cytoplasmic proteins. Our previous study showed that KPNA3 is involved in interferon production during PCV2 infection induced by Poly I:C and ISD (Interferon stimulatory DNA). However, it remains unclear whether PCV2 replication is associated with KPNA3. In the present study, knockdown of KPNA3 promoted the replication of PCV2, whereas overexpression of KPNA3 inhibited PCV2 replication in PK-15 cells. Furthermore, KPNA3 knockdown inhibited IRF3 and reduced the expression of antiviral genes including IFN-β, ISG54, Mx1 and ISG56, while the opposite results were obtained after KPNA3 overexpression. KPNA3 knockdown also promoted p65 nuclear translocation and increased the mRNA expression of IL-10 and IL-1β. These results suggested that KPNA3 facilitates IRF3 entry into the nucleus and the production of an antiviral response, resulting in PCV2 replication inhibition and blockage of NF-κB signal activation.

S. Pullorum is a causative agent of enteric disease of poultry with serious diarrhea. However, the detailed mechanism behind its injury to intestinal mucosa barrier, especially for intestinal stem cells, is unclear. In this study, S. Pullorum were orally administrated to 3 days old chicken to investigate the pathogenesis of S. Pullorum on intestinal mucosal barrier, especially on the proliferation of epithelial cells. We found that S. Pullorum could colonize in the cecum and invade into the liver through intestinal mucosa damage, which caused obvious pathological changes in liver and intestine and even leaded to death, as well as significant reduction of body weight. We also found that S. Pullorum infection enhanced the mRNA expression of IL-1β and IL-6 through TLR4/MyD88 pathway, which was also further verified by the increased lipopolysaccharide (LPS) levels in serum. Furthermore, S. Pullorum increased the depth of crypt and density of PCNA+ cells significantly through the over-activation of Wnt/β-catenin signaling pathway. The expression of intestinal stem cells markers Lgr5 and Bmi1 was also increased after S. Pullorum infection to support the crypt hyperplasia. In addition, we verified that S. Pullorum infection enhanced the mRNA expression of IL-1β, TLR4, Lgr5 and Bmi1. Our study indicated that S. Pullorum infection damaged the intestinal mucosa barrier to induce diarrhea, affected the abnormal proliferation of intestinal stem cells by over-activation of Wnt/β-catenin pathway in chicken.

蛋鸡养殖过程中涉及多种影响蛋鸡产蛋和蛋壳质量下降的疾病问题,其中蛋鸡前殖吸虫病是一种较为严重的流行性疾病。文章通过蛋鸡前殖吸虫病的临床症状、病理剖检变化观察、实验室诊断及治疗进行探讨,提出对蛋鸡前殖吸虫病的防治策略。