Toll-like receptor (TLR)3 signaling pathway is known to induce type 1 interferons (IFNs) and proinflammatory mediators leading to antiviral response against many viral infections. Double-stranded ribonucleic acid (dsRNA) has been shown to act as a ligand for TLR3 and, as such, has been a focus as a potential antiviral agent in many host-viral infection models. Yet, its effectiveness and involved mechanisms as a mediator against low pathogenic avian influenza virus (LPAIV) have not been investigated adequately. In this study, we used avian fibroblasts to verify whether dsRNA induces antiviral response against H4N6 LPAIV and clarify whether type 1 IFNs and proinflammatory mediators such as interleukin (IL)-1β are contributing to the dsRNA-mediated antiviral response against H4N6 LPAIV. We found that dsRNA induces antiviral response in avian fibroblasts against H4N6 LPAIV infection. The treatment of avian fibroblasts with dsRNA increases the expressions of TLR3, IFN-α, IFN-β, and IL-1β. We also confirmed that this antiviral response elicited against H4N6 LPAIV infection correlates, but is not attributable to type 1 IFNs or IL-1β. Our findings imply that the TLR3 ligand, dsRNA, can elicit antiviral response in avian fibroblasts against LPAIV infection, highlighting potential value of dsRNA as an antiviral agent against LPAIV infections. However, further investigations are required to determine the potential role of other innate immune mediators or combination of the tested cytokines in the dsRNA-mediated antiviral response against H4N6 LPAIV infection.
Keywords: antiviral response; avian fibroblast; avian influenza virus; dsRNA; interleukin 1β; toll-like receptor 3; type 1 interferon.