Browsing by Author "Mohamed Abdul Cader, Mohamed Sarjoon"
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Item Open Access Activation of Toll-Like Receptor-Mediated Antiviral Response Against Infectious Laryngotracheitis Virus Infection(2023-09-21) Mohamed Abdul Cader, Mohamed Sarjoon; Abdul-Careem, Mohamed Faizal; van der Meer, Frank; Van Marle, Guido; Gomis, SusanthaInfectious laryngotracheitis virus (ILTV) is a highly prevalent avian respiratory virus in Canada and globally, which can cause mild to severe respiratory illnesses. Although the live attenuated ILTV vaccines are commonly used for control, they pose challenges such as establishing lifelong latent infections, reactivating and shedding latent viruses, and regaining virulence in vaccine strains. Therefore, it is essential to develop novel control measures to address the limitations of current approaches. Inducing innate antiviral responses via the activation of toll-like receptors (TLRs) is a promising strategy for reducing ILTV replication. Endosomal TLRs in chickens, such as TLR7 and TLR21, recognize viral genetic materials, while surface TLRs (e.g., TLR4) primarily recognize bacterial molecules, but may also contribute to antiviral responses by recognizing viral proteins. Synthetic TLR ligands have been shown to induce antiviral responses against some avian viruses, such as avian influenza virus (AIV), infectious bursal disease virus (IBDV), ILTV, and infectious bronchitis virus (IBV). However, the impacts of in-ovo delivery of endosomal TLR7 and TLR21 ligands and surface TLR4 ligand (single-stranded (ss) RNA, cytosine-guanosine deoxynucleotides (CpG) DNA, and lipopolysaccharide (LPS), respectively) in reducing ILTV replication in chickens post-hatch through induction of antiviral responses is unknown. This thesis aimed to study the enhanced immune response following in-ovo treatment of these TLR ligands against ILTV infection in young chickens. Our hypothesis is that in-ovo delivery of these ligands will enhance antiviral immune responses and reduce ILTV replication in chickens post-hatch. Our results confirmed the following findings: Firstly, the in-ovo administration of synthetic TLR7 ligand, resiquimod, reduces ILTV shedding post-hatch, correlating with enhanced macrophage responses. Secondly, the in-ovo delivered CpG DNA stimulates cellular immune responses in multiple organs post-hatch, potentially reducing ILTV infection. Thirdly, the in-ovo LPS treatment stimulates protective antiviral responses against ILTV infection post-hatch, correlating with the expansion of macrophage population in the lungs. Overall, the studies provide insights into the mechanisms of host responses elicited following in-ovo delivery of these three TLR ligands against ILTV in chickens. The outcomes of the current studies can be helpful in fine-tuning the currently used vaccine strategies against ILTV in chicken to achieve maximum protection.Item Open Access Cytosine-guanosine deoxynucleotides (CpG DNA)-mediated Antiviral Response Against Avian Influenza Virus Infection(2016) Mohamed Abdul Cader, Mohamed Sarjoon; Abdul-Careem, Faizal; Schaetzl, Hermann; Fonseca, Kevin; Liljebjelke, KarenCytosine-guanosine deoxynucleotides (CpG DNA) can be used for the stimulation of toll-like receptor (TLR)21 signaling pathway in avian species, that ultimately leads to upregulation of gene transcription for pro-inflammatory molecules including nitric oxide (NO) and recruitment of innate immune cells. These innate immune mediators, play various roles in the innate immune system against viruses that infect mammals and avian species. The objective of the study was to determine the antiviral effect of NO, produced in response to in ovo delivery of CpG DNA, against H4N6 low pathogenic avian influenza virus (LPAIV) infection in the avian respiratory system. First, we observed that when CpG DNA is delivered at embryo day (ED)18 in ovo and subsequently challenged with H4N6 LPAIV at ED19 pre-hatch and day 1 post-hatch, CpG DNA reduces H4N6 LPAIV replication in the respiratory tract. Second, we observed that CpG DNA-mediated H4N6 LPAIV inhibition was attributable to NO production. Third, we observed that the antiviral response elicited by in ovo CpG DNA delivery is also associated with macrophage recruitment in the lungs. Finally, we showed that NO originated from macrophages is capable of eliciting antiviral response against H4N6 LPAIV infection in a dose-dependent manner. Altogether, CpG DNA-mediated antiviral response against H4N6 LPAIV infection is attributable to increased macrophage numbers in the lungs and elevated NO production originated from macrophages. The study provides insights into the mechanisms of CpG DNA-mediated antiviral response, particularly against H4N6 LPAIV infection in avian species.