Duck Enteritis Virus VP16 Antagonizes IFN-β-Mediated Antiviral Innate Immunity

Abstract

Duck enteritis virus (DEV) can successfully evade the host innate immune responses and establish a lifelong latent infection in the infected host. However, the study about how DEV escapes host innate immunity is still deficient up to now. In this study, for the first time, we identified a viral protein VP16 by which DEV can obviously downregulate the production of IFN-β in duck embryo fibroblast (DEF). Our results showed that ectopic expression of VP16 decreased duck IFN-β (duIFN-β) promoter activation and significantly inhibited the mRNA transcription of IFN-β. Further study showed that VP16 can also obviously inhibit the mRNA transcription of interferon-stimulated genes (ISGs), such as myxovirus resistance protein (Mx) and interferon-induced oligoadenylate synthetase-like (OASL). Furthermore, we found that this anti-interferon activity of VP16 depended on its N-terminus (aa1-200). Coexpression analysis revealed that VP16 selectively blocked duIFN-β promoter activity at the duIRF7 level rather than duIRF1. Based on the results of coimmunoprecipitation analysis (co-IP) and indirect immunofluorescence assay (IFA), VP16 was able to bind to duck IRF7 (duIRF7) directly, but did not interact with duck IRF1 (duIRF1) in vitro.

Duck Enteritis Virus Protein Kinase US3 Inhibits DNA Sensing Signaling by Phosphorylating Interferon Regulatory Factor 7

“…Duck STING is vital for duck IFN-I induction and plays an important role in the host defense against DEV infection ( 40 ). Moreover, the DEV VP16 protein inhibits DNA sensing by interacting with duck IRF7 ( 22 ). However, it remains unclear whether other DEV viral proteins are involved in the antagonization of the DNA sensing pathway.…”

“…Comparatively, chicken, duck, and goose cGAS exhibit shortened N termini with 22.4%, 17.4%, and 7.7% similarity to human cGAS, respectively ( 19 , 20 ). As in mammals, the cGAS-STING axis plays a critical role in restricting DNA virus infection in chicken and duck cells ( 21 , 22 ). Recently, the DEV VP16 protein was shown to inhibit DNA sensing by interacting with duck IRF7 ( 22 ).…”

“…As in mammals, the cGAS-STING axis plays a critical role in restricting DNA virus infection in chicken and duck cells ( 21 , 22 ). Recently, the DEV VP16 protein was shown to inhibit DNA sensing by interacting with duck IRF7 ( 22 ). However, it remains unclear whether other DEV viral proteins are involved in the antagonization of the DNA sensing pathway.…”

Mechanism of herpesvirus UL24 protein regulating viral immune escape and virulence

“…To break through this innate immune response and proliferate effectively in host cells, herpesviruses have evolved numerous ways to resist the innate immune response of the host. One of the most important strategies is immune escape ( Kolb et al, 2016 ; Li et al, 2020 ; Zhu and Zheng, 2020 ; He et al, 2022 ; Kong et al, 2022 ). UL24, as a viral tegument protein, has been shown to act on multiple immune signaling pathways to participate in immune escape from the host antiviral response ( Table 1 ).…”