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Infectious bursal disease virus (IBDV) is an acute and highly infectious RNA virus known for its immunosuppressive capabilities, chiefly inflicting rapid damage to the bursa of Fabricius (BF) of chickens. Current clinical control of IBDV infection relies on vaccination. However, the emergence of novel variant IBDV (nVarIBDV) has posed a threat to the poultry industry across the globe, underscoring the great demand for innovative and effective vaccines. Our previous studies have highlighted the critical role of IBDV VP5 as an apoptosis-inducer in host cells. In this study, we engineered IBDV mutants via a reverse genetic system to introduce amino acid mutations in VP5. We found that the mutant IBDV-VP5/3m strain caused reduced host cell mortality, and that strategic mutations in VP5 reduced IBDV replication early after infection, thereby delaying cell death. Furthermore, inoculation of chickens with IBDV-VP5/3m effectively reduced damage to BF and induced neutralizing antibody production comparable to that of parental IBDV WT strain. Importantly, vaccination with IBDV-VP5/3m protected chickens against challenges with nVarIBDV, an emerging IBDV variant strain in China, reducing nVarIBDV loads in BF while alleviating bursal atrophy and splenomegaly, suggesting that IBDV-VP5/3m might serve as a novel vaccine candidate that could be further developed as an effective vaccine for clinical control of IBD. This study provides a new clue to the development of novel and effective vaccines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Avian reovirus (ARV) is a significant pathogen that causes various clinical diseases in chickens, including viral arthritis, chronic respiratory diseases, retarded growth, and malabsorption syndrome. These conditions result in substantial economic losses for the global poultry industry. MicroRNAs (miRNAs), a type of small noncoding RNAs that regulate gene expression post transcriptionally by silencing or degrading their RNA targets, play crucial roles in response to pathogenic infections. In this study, transfection of DF-1 cells with gga-miR-200a-3p, an upregulated miRNA observed in ARV-infected cells, significantly suppressed ARV-induced apoptosis by directly targeting GRB2 and impeded ARV replication. Conversely, knockdown of endogenous gga-miR-200a-3p in DF-1 cells using a specific miRNA inhibitor enhanced ARV-induced apoptosis and promoted GRB2 expression, thereby facilitating viral growth within cells. Consistently, inhibition of GRB2 activity through siRNA-mediated knockdown reduced viral titers. Therefore, gga-miR-200a-3p plays a vital antiviral role in the host response to ARV infection by suppressing apoptosis via direct targeting of GRB2 protein. This information enhances our understanding of the mechanisms by which host cells combat against ARV infection through self-encoded small RNA molecules and expands our knowledge regarding the involvement of microRNAs in the host response to pathogenic infections., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yongqiang Wang reports financial support was provided by National Natural Science Foundation of China and Earmarked Fund for Modern Agro-Industry Technology Research System of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Avian reovirus (ARV) is the causative agent of avian viral arthritis and causes significant economic losses to the global poultry industry. For clinical diagnosis, detecting ARV-specific antibodies is crucial. We successfully expressed the ARV-σC protein in insect cells using the baculovirus expression vector system, achieving an expression level of approximately 200 mg/L. We developed an indirect enzyme-linked immunosorbent assay (iELISA) using the ARV-σC protein as a coating antigen to detect antibodies against it. The inter-batch and intrabatch coefficients of iELISA variation were less than 10%. Its sensitivity (1:12,800 diluted in serum) was 4 times higher than that of the indirect immunofluorescence assay (IFA; 1:3200 diluted in serum), and it showed no cross-reactivity with antibodies against other common avian viruses (such as Infectious bursal disease virus, Newcastle disease virus). The practicality of the iELISA was further evaluated using clinical samples. 300 clinical sera from chickens vaccinated with the ARV attenuated vaccine and 20 SPF sera were tested using both the iELISA and the IFA, demonstrating a 100% conformity rate. In conclusion, these results suggest that the iELISA developed in this study is a rapid, sensitive, and specific method that could serve as an effective diagnostic tool for monitoring and controlling avian viral arthritis., Competing Interests: DISCLOSURES All authors disclosed no relevant relationships., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Pyroptosis is an inflammatory type of programmed cell death predominantly driven by the formation of plasma membrane pores by the N-terminus generated from the cleaved Gasdermin (GSDM) family proteins. Examination of membrane-attached GSDM- NT by Western Blot is the most commonly used method for evaluating pyroptosis. However, it is difficult to differentiate cells with pyroptosis from other forms of cell death using this method. In this study, Infectious Bursal Disease Virus (IBDV)-infected DF-1 cells were employed as a model to quantify the proportion of cells undergoing pyroptosis by flow cytometry, utilizing specific antibodies against the N-terminal fragment of chicken GSDME (chGSDME- NT ) and propidium iodide (PI) staining. The chGSDME- NT -positive cells were readily detectable by flow cytometry using Alexa Fluor 647-labeled anti-chGSDME- NT antibodies. Moreover, the proportion of chGSDME- NT /PI double-positive cells in IBDV-infected cells (around 33%) was significantly greater than in mock-infected controls (P < 0.001). These findings indicate that examination of membrane-bound chGSDME- NT by flow cytometry is an effective approach for determining pyroptotic cells among cells undergoing cell death.

Fowl Adenoviruses (FAdVs) are widely-distributed pathogens across the globe. Fowl adenovirus serotype 4 (FAdV-4), the causative agent for chicken hydropericardium syndrome (HPS) with a high mortality in the infected flocks, has caused severe economic losses to the poultry industry of China in the past few years. Although vaccination against FAdV-4 has been implemented, the prevention and control of FAdV-4 infection is still not very successful. Here, we report that FAdV-4 markedly inhibits Leghorn male hepatoma (LMH) cell growth and this inhibition could be abolished by a small molecule SP600125, a JNK MAPK specific inhibitor. Furthermore, SP600125 considerably suppressed FAdV-4-induced phosphorylation of p38 and JNK MAPK. Importantly, SP600125 promoted type I interferon production associated with inhibition of FAdV-4 replication. Thus, FAdV-4 might employ the JNK MAPK pathway for the benefit of its replication, and SP600125 may have the potential of being used as an anti-virus drug for the control FAdV-4 infection., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Extraintestinal pathogenic Escherichia coli (ExPEC) are important human pathogens responsible for urinary tract infection and meningitis. Therefore, infection of chickens by highly pathogenic E. coli with multi-drug resistance has become a major concern to food safety. In this study, we isolated a strain of E. coli (HB2016) from the oviduct of a diseased chicken with colibacillosis. Inoculation of chickens with 2 × 10 6  CFU of the isolate E. coli HB2016 by intraperitoneal injection successfully reproduced colibacillosis in chickens. We also found that E. coli HB2016 harbored four more virulence genes (tsh, trat, cvaC and cvaA/B) than E. coli reference strain CVCC1428. Importantly, E. coli HB2016 was resistant to cefuroxime, tobramycin, medemycin, cefazolin, cefoperazone, streptomycin and ampicillin, and carried multiple antibiotic resistance genes such as strA, strB, bla CMY-2 , bla CTX-M-19 , bla TEM-1B , fosA, mph(A), floR, sul2, tet(A) and tet(B). These findings suggest that the causative E. coli act as a potential zoonotic agent affecting human health., (Copyright © 2018. Published by Elsevier B.V.)

Viruses have developed a variety of methods to evade host immune response. Our previous study showed that infectious bursal disease virus (IBDV) inhibited type I interferon production via interaction of VP4 with cellular glucocorticoid-induced leucine zipper (GILZ) protein. However, the exact underlying molecular mechanism is still unclear. In this study, we found that IBDV VP4 suppressed GILZ degradation by inhibiting K48-linked ubiquitylation of GILZ. Furthermore, mutation of VP4 (R41G) abolished the inhibitory effect of VP4 on IFN-β expression and GILZ ubiquitylation, indicating that the amino acid 41R of VP4 was required for the suppression of IFN-β expression and GILZ ubiquitylation. Moreover, IBDV infection or VP4 expression markedly inhibited endogenous GILZ ubiquitylation. Thus, IBDV VP4 suppresses type I interferon expression by inhibiting K48-linked ubiquitylation of GILZ, revealing a new mechanism employed by IBDV to suppress host response., (Copyright © 2017. Published by Elsevier GmbH.)

MicroRNAs (miRNAs) are a class of non-coding small RNAs that play important roles in the regulation of various biological processes including cell development and differentiation, apoptosis, tumorigenesis, immunoregulation and viral infections. Avian immunosuppressive diseases refer to those avian diseases caused by pathogens that target and damage the immune organs or cells of the host, increasing susceptibility to other microbial infections and the risk of failure in subsequent vaccination against other diseases. As such, once a disease with an immunosuppressive feature occurs in flocks, it would be difficult for the stakeholders to have an optimal economic income. Infectious bursal disease (IBD), avian leukemia (AL), Marek's disease (MD), chicken infectious anemia (CIA), reticuloendotheliosis (RE) and avian reovirus infection are on the top list of commonly-seen avian diseases with a feature of immunosuppression, posing an unmeasurable threat to the poultry industry across the globe. Understanding the pathogenesis of avian immunosuppressive disease is the basis for disease prevention and control. miRNAs have been shown to be involved in host response to pathogenic infections in chickens, including regulation of immunity, tumorigenesis, cell proliferation and viral replication. Here we summarize current knowledge on the roles of miRNAs in avian response to viral infection and pathogenesis of avian immunosuppressive diseases, in particular, MD, AL, IBD and RE. [ABSTRACT FROM AUTHOR]

• CIAV VP1 protein inhibits IFN-I expression induced by cGAS-STING signaling. • VP1 inhibits TBK1 phosphorylation. • The 121–150 aa in VP1 is essential for VP1 to interact with TBK1 and inhibit cGAS-STING signaling. Chicken infectious anemia virus (CIAV) infection induces immunosuppression or subclinical immunosuppression in chickens. CIAV infection has been reported to repress type I interferon (IFN-I) expression, but the underlying mechanisms are not yet understood. Here we reported that VP1, the capsid protein of CIAV, the major immunogenic protein that triggers the production of neutralizing antibodies in chickens, inhibited type I interferon (IFN-I) expression induced by cGAS-STING signaling. We showed that VP1 inhibited TBK1 phosphorylation and down stream signal transduction, leading to the inhibition of IFN-I expression. Subsequently, we demonstrated that VP1 interacted with TBK1. Finally, we clarified that aa 120–150 in VP1 was essential for VP1 to interact with TBK1 and inhibit cGAS-STING signaling. These findings will help us further understand the pathogenesis of CIAV in chickens. [ABSTRACT FROM AUTHOR]