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Iran J Vet Res. 2021;22(3):209-216. doi: 10.22099/ijvr.2021.38240.5568.

The dUTPase of caprine arthritis-encephalitis virus negatively regulates interferon signaling pathway.

Iranian journal of veterinary research

J Shi, X Li, M Zhu, H Chi, Y Song, J Wang, J Huang

Affiliations

  1. MSc Student in Biology, Department of Microbiology & Immunology, School of Life Sciences, Tianjin University, Tianjin, 300072, China.
  2. These authors contributed equally to this work.
  3. Departmet of Microbiology & Immunology, School of Life Sciences, Tianjin University, Tianjin, 300072, China.

PMID: 34777521 PMCID: PMC8573393 DOI: 10.22099/ijvr.2021.38240.5568

Abstract

BACKGROUND: Deoxyuracil triphosphate nucleotide (dUTP) pyrophosphatase (dUTPase, DU) is an enzyme of caprine arthritis-encephalitis virus (CAEV) that minimizes incorporation of dUTP into the DNA. Caprine arthritis-encephalitis virus relies partly on its ability to escape from innate immunity to cause persistent infections. Interferon β (IFN-β) is an important marker for evaluating the innate immune system, and it has a broad spectrum of antiviral activity.

AIMS: This study was conducted to investigate the details of the IFN-β response to CAEV infection.

METHODS: The expression of IFN-β and the proliferation of Sendai virus (SeV) and vesicular stomatitis virus (VSV) were determined by real-time quantitative polymerase chain reaction (qPCR). The effect of DU on the IFN signaling pathway was evaluated using luciferase reporter assays.

RESULTS: In our study, the expression of IFN-β was significantly inhibited and the proliferation of SeV and VSV was promoted in cells overexpressing CAEV-DU. DU affected interferon stimulated response element (ISRE) and IFN-β promoter activities induced by RIG-I/MDA5/MAVS/TBK1 pathway, while did not affect them induced by interferon regulatory factor 3 (IRF3-5D).

CONCLUSION: DU protein downregulated the production of IFN-β by inhibiting the activity of the signal transduction molecules upstream of IRF3, thereby, helping CAEV escape innate immunity. Findings of this work provide an evidence to understand the persistent infection and multiple system inflammation of CAEV.

Keywords: Caprine arthritis-encephalitis virus; Innate immunity; Interferon type I; dUTPase

Conflict of interest statement

The authors declare no financial and/or non-financial competing interests.

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