Activation of Toll-Like Receptor-Mediated Antiviral Response Against Infectious Laryngotracheitis Virus Infection
Date
2023-09-21
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Abstract
Infectious 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.
Description
Keywords
Toll-like receptors,, Respiratory Virus, ILTV, CpG, ssRNA, LPS
Citation
Mohamed Abdul Cader, M. S. (2023). Activation of toll-like receptor-mediated antiviral response against infectious laryngotracheitis virus infection (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.