The Vif protein of caprine arthritis encephalitis virus inhibits interferon production

Caprine arthritis-encephalitis (CAE) is a chronic progressive infectious disease caused by caprine arthritis-encephalitis virus (CAEV) that seriously threatens the goat industry. Chronic infection and life-long multi-tissue inflammation are the typical features of the disease. Innate antiviral immunity is essential for the host defense system that rapidly recognizes and eliminates invading viruses. Interferon β (IFN-β) is important for innate immunity and regulates immunity against a broad spectrum of viruses. To investigate the details of the IFN-β response to CAEV infection, the effects of six viral proteins and the molecular mechanisms by which they affect IFN-β production were analyzed. Overexpression of DU and Vif promote virus proliferation and inhibit the production of IFN-β. qRT-PCR and luciferase reporter assays showed that overexpression of Vif inhibits the expression of luciferase under the control of the ISRE, NF-κB or IFN-β promoter but does not affect the expression of IFN-β activated by IRF3, indicating that Vif negatively regulates IFN-β production by affecting upstream signal transduction of IRF3. Amino acids 149-164 of Vif were found to be necessary for the inhibitory effect of IFN-β production. Our results indicate that CAEV evades surveillance and clearance by intracellular innate immunity by downregulating IFN-β production.