الفهرس 
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Abstract
Influenza A viruses (IAVs) are important pathogens of humans and many other species, as, these viruses have been widely circulating in animals are novel to the human immune system; so pose a potential threat to public health. Moreover, recently, low-pathogenic avian influenza viruses (LPAIVs) have caused a global concern to public health therefore attention should be paid to the potential threats to humans posed by LPAIVs. As well as there is an urgent need to more efficient strategies for the prevention and control of such infection. Double stranded ribonucleic acid (dsRNA) has been shown to act as a ligand for Toll like receptor (TLR3) that known to induce type 1 interferons (IFNs) and pro-inflammatory mediators leading to antiviral response against many viral infections. Yet, its effectiveness and involved mechanisms as a mediator against low LPAIV have not been investigated adequately. Therefore, this study was attempted to investigate the effect and mechanism of dsRNA as anti- H4N6 LPAIV. Among those, the pre-hatch treatment of specific pathogen free eggs (at 18 days) with dsRNA was performed and evidenced the reduction of H4N6 replication in lungs by plaque assay. Further studies revealed that the in ovo delivery of dsRNA increases TLR3 expression, type I IFN production and number of macrophages using immunostaining assay in addition to mRNA expression of IL-1 using RT-PCR in lung 24-hours post-treatment. The same level of induction of innate response was not evident in the spleen. Additionally, the treatment of avian fibroblasts with dsRNA induces antiviral response in avian fibroblasts against H4N6 LPAIV through increases the expressions of TLR3, IFN-, IFN- and IL-1 using immunostaining assay. As well as this study emphasized that this antiviral response elicited against H4N6 LPAIV infection correlates but is not attributable to type 1 IFNs or IL-1. These results imply that the TLR3 ligand, dsRNA has antiviral activity in ovo and in vitro against LPAIV highlighting potential value of dsRNA as an antiviral agent against LPAIV infections. Although H4 AIVs are low pathogenic AIVs, it is possible that they will eventually gain the ability to transmit efficiently through the accumulation of mutations and reassortments. Therefore, 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 to prepare for potential pandemics.