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

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.

SUBMITTER: Shi J 

PROVIDER: S-EPMC8573393 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature