TBK1 Mediates Innate Antiviral Immune Response against Duck Enteritis Virus

Abstract

Duck enteritis virus (DEV) can infect several types of waterfowl can cause high mortality and huge economic losses to the global waterfowl industry. Type I interferons (IFN) are important for host defense against virus infection through induction of antiviral effector molecules. TANK-binding kinase 1 (TBK1) is a key kinase required for the induction of type I IFNs; however, the role of TBK1 on DEV infection remains unclear. Here, we observed that the expression levels of TBK1 and IFN-β were upregulated during DEV infection in vivo and in vitro. Thus, the function of TBK1 on DEV infection was determined. The results showed that overexpression of TBK1 reduced DEV infection and knockdown of TBK1 resulted in the increased of DEV infection. Additionally, TBK1 overexpression upregulated the expression of IFN-β and a few interferon-stimulated genes (ISGs), which thus inhibited the synthesis of DEV glycoprotein B. On the other hand, the TBK1 inhibitor Amlexanox down-regulated the expression levels of IFN-β and IRF3. Interestingly, the expression levels of MAVS and GSK-3β were decreased in the cells treated with Amlexanox. Furthermore, overexpression of TBK1 activated the expression of upstream molecules MAVS and GSK-3β. Whereas, the expression of TBK1, IRF3 and IFN-β was inhibited by the GSK-3β inhibitor SB216763. Our findings suggest that DEV–stimulated TBK1 may be involved in defense against DEV infection.

Chicken Glycogen Synthase Kinase 3β Suppresses Innate Immune Responses and Enhances Avian Leukosis Virus Replication in DF-1 Cells

“…In previous reports, overexpression of GSK3β was reported to enhance the activation of IRF3 and the transcription of IFN-β by Sendai virus (SeV), and this effect is produced by GSK3β by causing oligomerization and phosphorylation of TANK-binding kinase 1 (TBK1) ( 36 ). It was also reported that GSK3β can interact directly with TBK1 ( 37 ) to promote TBK1 phosphorylation ( 38 ) and that overexpression of TBK1 in DEF cells causes activation of GSK3β ( 39 ). In this study, whether the mechanism of chGSK3β affecting ALV-J replication is also related to TBK1 needs to be clarified by further studies.…”

Histone deacetylase 6’s function in viral infection, innate immunity, and disease: latest advances

“…Recent research shows that HDAC6 controls the phosphorylation of TBK1 and Akt in macrophages by poly (I:C) ( 23 ). Reports show that when double-stranded RNA (dsRNA) binds to TLR3, it turns on TBK1 and starts signaling transduction that leads to the production of IFN-I ( 98 – 101 ). The cell signaling molecule Akt also interacts with MT ( 102 , 103 ).…”

“…Recent research has demonstrated that the suppression of HDAC6 greatly increases the amount of acetylation of a-tubulin, which enhances the fusion and reproduction of human parainfluenza virus type 3 (HPIV3) (66). TANK-binding kinase 1 (TBK1), an IKKrelated serine/threonine kinase, plays a big role in antiviral immunity (98)(99)(100)(101). Recent research shows that HDAC6 controls the phosphorylation of TBK1 and Akt in macrophages by poly (I:C) (23).…”

Untargeted metabolomics of the intestinal tract of DEV-infected ducks

“…Author details 1 School of Animal Science, Guizhou University, Guiyang, China. 2 Guizhou Provincial Animal Biological Products Engineering Technology Research Center, Guiyang, China. • support for research data, including large and complex data types • gold Open Access which fosters wider collaboration and increased citations maximum visibility for your research: over 100M website views per year…”

“…It can cause acute septic and highly contagious infectious disease in ducks, geese, and a variety of Anseridae poultry. DEV is an important pathogen that seriously threatens the development of the duck industry [2]. It mainly replicates in the mucosa of the digestive tract and then spreads to the bursa, thymus, spleen and liver [3].…”