Browsing by Author "Nagy, Eva"

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    Antiviral response elicited against avian influenza virus infection following activation of toll-like receptor (TLR)7 signaling pathway is attributable to interleukin (IL)-1β production
    (2018-12-04) Abdul-Cader, Mohamed S; De Silva Senapathi, Upasama; Nagy, Eva; Sharif, Shayan; Abdul-Careem, Mohamed F
    Abstract Objective Single stranded ribonucleic acid (ssRNA) binds to toll-like receptor (TLR)7 leading to recruitment of immune cells and production of pro-inflammatory cytokines, which has been shown in mammals. In chickens, ssRNA has been shown to elicit antiviral response against infectious bursal disease virus infection. The objectives of this study were to determine the pro-inflammatory mediators that are activated downstream of TLR7 signaling pathway in avian macrophages and their roles in antiviral response against avian influenza virus (AIV) infection. Results In this study, first, we stimulated avian macrophages with the analog of ssRNA, resiquimod, and found that the ssRNA was capable of increasing nitric oxide (NO) and interleukin (IL-1β) production in avian macrophages. Second, we observed when the avian macrophages were stimulated with ssRNA, it elicits an antiviral response against AIV. Finally, we demonstrated that when we blocked the IL-1β response using IL-1 receptor antagonist (IL-1Ra) and the NO production using a selective inhibitor of inducible nitric oxide synthase (iNOS), N-([3-(aminomethyl)phenyl]methyl)ethanimidamide dihydrochloride (1400 W), the antiviral response against AIV is attributable to IL-1β production and not to the NO production. This study provides insights into the mechanisms of antiviral response mediated by ssRNA, particularly against AIV infection.
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    Potential mediators of in ovo delivered double stranded (ds) RNA-induced innate response against low pathogenic avian influenza virus infection
    (2018-03-12) Ahmed-Hassan, Hanaa; Abdul-Cader, Mohamed S; De Silva Senapathi, Upasama; Sabry, Maha A; Hamza, Eman; Nagy, Eva; Sharif, Shayan; Abdul-Careem, Mohamed F
    Abstract Background Toll like receptor (TLR) 3 is a critically important innate pattern recognizing receptor that senses many viral infections. Although, it has been shown that double stranded (ds) RNA can be used for the stimulation of TLR3 signaling pathway in a number of host-viral infection models, it’s effectiveness as an antiviral agent against low pathogenic avian influenza virus (LPAIV) needs further investigation. Methods In this study, first, we delivered TLR3 ligand, dsRNA, in ovo at embryo day (ED)18 since in ovo route is routinely used for vaccination against poultry viral and parasitic infections and infected with H4N6 LPAIV 24-h post-treatment. A subset of in ovo dsRNA treated and control groups were observed for the expressions of TLR3 and type I interferon (IFN)s, mRNA expression of interleukin (IL)-1β and macrophage recruitment coinciding with the time of H4N6 LPAIV infection (24 h post-treatment). Additionally, Day 1 chickens were given dsRNA intra-tracheally along with a control group and a subset of chickens were infected with H4N6 LPAIV 24-h post-treatment whereas the rest of the animals were observed for macrophage and type 1 IFN responses coinciding with the time of viral infection. Results Our results demonstrate that the pre-hatch treatment of eggs with dsRNA reduces H4N6 replication in lungs. Further studies revealed that in ovo delivery of dsRNA increases TLR3 expression, type I IFN production and number of macrophages in addition to mRNA expression of IL-1β in lung 24-h post-treatment. The same level of induction of innate response was not evident in the spleen. Moreover, we discovered that dsRNA elicits antiviral response against LPAIV correlating with type I IFN activity in macrophages in vitro. Post-hatch, we found no difference in H4N6 LPAIV genome loads between dsRNA treated and control chickens although we observed higher macrophage recruitment and IFN-β response coinciding with the time of viral infection. Conclusions Our findings imply that the TLR3 ligand, dsRNA has antiviral activity in ovo and in vitro but not in chickens post-hatch and dsRNA-mediated innate host response is characterized by macrophage recruitment and expressions of TLR3 and type 1 IFNs.