Investigation of the antiviral activity of duck viperin against influenza A virus

Ducks are the natural reservoir of influenza A virus. Normally, the virus replicates in their intestine and is passed in the feces, although highly pathogenic influenza A virus replicates in the lungs. Influenza infection in ducks is frequently asymptomatic. During infection with highly pathogenic avian influenza H5N1, viperin (virus-induced protein endoplasmic reticulum-associated interferon-inducible) was the most up-regulated innate immune gene in the duck lungs but was not upregulated in the duck intestine. Here we determined the effect of duck viperin on influenza A virus during infection. Chicken fibroblast cells stably expressing duck viperin or vector only were infected with low pathogenic influenza A virus A/chicken/CA/431/2000. Viperin decreased the viral titre after 24, 48 and 72 hours of infection. Viperin was suspected to decrease the lipid rafts through interacting with farnesyl diphosphate synthase. Using confocal microscopy and flow cytometry, we showed that duck viperin expression decreased the lipid rafts in the chicken fibroblast cells. The addition of exogenous farnesol, which works downstream of farnesyl diphosphate synthase, reversed the antiviral effect of duck viperin. Finally, we identified the critical regions and residues important for function of duck viperin. The central domain contains radical S-Adenosyl methionine motifs, mutation of which leads to loss of viperin antiviral effect. Viperin, which is induced by highly pathogenic influenza A virus, has an antiviral function.