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DDX1 from Cherry valley duck mediates signaling pathways and anti-NDRV activity.

ABSTRACT: Novel duck reovirus (NDRV) causes severe economic losses to the duck industry, which is characterized by hemorrhagic spots and necrotic foci of the livers and spleens. DEAD-box helicase 1 (DDX1) plays a critical role in the innate immune system against viral infection. However, the role of duck DDX1 (duDDX1) in anti-RNA virus infection, especially in the anti-NDRV infection, has yet to be elucidated. In the present study, the full-length cDNA of duDDX1 (2223 bp encode 740 amino acids) was firstly cloned from the spleen of healthy Cherry valley ducks, and the phylogenetic tree indicated that the duDDX1 has the closest relationship with Anas platyrhynchos in the bird branch. The duDDX1 mRNA was widely distributed in all tested tissues, especially in the duodenum, liver, and spleen. Overexpression of duDDX1 in primary duck embryo fibroblast (DEF) cells triggered the activation of transcription factors IRF-7 and NF-κB, as well as IFN-β expression, and the expression of the Toll-like receptors (TLR2, TLR3, and TLR4) was significantly increased. Importantly, after overexpressing or knocking down duDDX1 and infecting NDRV in DEF cells, duDDX1 inhibits the replication of NDRV virus and also regulates the expression of pattern recognition receptors and cytokines. This indicates that duDDX1 may play an important role in the innate immune response of ducks to NDRV. Collectively, we first cloned DDX1 from ducks and analyzed its biological functions. Secondly, we proved that duck DDX1 participates in anti-NDRV infection, and innovated new ideas for the prevention and control of duck virus infection.

SUBMITTER: Zhang H

PROVIDER: S-EPMC7816157 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAlthough several studies have revealed that the sensitivity of ducklings to duck Tembusu virus (DTMUV) was related to age, however, DTMUV was originally isolated from egg-laying ducks, and the ovary was the target organ of this virus. Cherry Valley breeding ducks aged 15- and 55-week-old (they are reserve breeding ducks and the normal egg-laying breeding ducks, respectively) were infected with DTMUV, using intramuscular injection, to study the effect of age-related difference on the pathogenicity of DTMUV in breeding ducks.ResultsExaminations of clinical symptoms, gross and microscopic lesions, viral loads, cytokines and serum neutralizing antibodies were performed. Results showed that obvious clinical symptoms, such as depression, ruffled feathers, ataxia and egg-laying drop were observed in the 55-week-old laying ducks, with five ducks dying at 5-7 days post infection (dpi). The 15-week-old ducks showed slight symptoms during infection. Gross lesions were severe and characterized by the congestion, hemorrhage and swelling of some organs in the 55-week-old ducks, including the hemorrhage of endocardium, hepatomegaly, splenomegaly, oviduct hemorrhage, hyperemia and deformation of the ovary. Mild endocardial hemorrhage and hepatosplenomegaly were observed in the 15-week-old ducks. Similarly, there was a significant difference in microscopic lesions between the two groups. The older ducks displayed severe microscopic lesions, specifically in the hemorrhage, interstitial inflammatory cell infiltration of the endocardium, typical viral encephalitis and hemorrhage in the ovary. But on the whole, the 15-week-old ducks showed milder lesions. Viral loads in tissues of the older group were significantly higher than those of the younger group. The levels of interferon (IFN)-γ, interleukin (IL)-2 and neutralizing antibody in the 15-week-old ducks were higher than in the 55-week-old ducks at the early stage of the DTMUV infection, suggesting the immune response in the younger ducks to DTMUV was stronger than in the older ducks.ConclusionsThese results demonstrated that age-related differences in susceptibility to DTMUV in breeding ducks was significant, with 55-week-old egg-laying ducks being more susceptible to DTMUV than 15-week-old reserve breeding ducks.

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DDX1 from Cherry valley duck mediates signaling pathways and anti-NDRV activity.

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