Antiviral Response Against Avian Influenza Virus and Avian Infectious Bronchitis Virus: Focus on MicroRNA Regulation

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dc.contributor.advisorAbdul-Careem, Mohamed Faizal
dc.contributor.advisorGagnon, Carl A.
dc.contributor.authorO'Dowd, Kelsey
dc.contributor.committeemembervan der Meer, Franciscus Johannes
dc.contributor.committeememberNiu, Dongyan Xu
dc.contributor.committeememberNiikura, Masahiro
dc.contributor.committeememberSusta, Leonardo
dc.date2024-05
dc.date.accessioned2024-04-30T22:42:26Z
dc.date.available2024-04-30T22:42:26Z
dc.date.issued2024-04-29
dc.description.abstractAvian influenza virus (AIV) and avian infectious bronchitis virus (IBV) are respiratory RNA viruses with significant economic implications due to morbidity, mortality, secondary bacterial infections, and overall decreased flock performances. Current AIV and IBV control methods have limitations and new variants continue to emerge; therefore, there is a need to develop new control strategies and gain a better understanding of host-pathogen interactions during the early stages of viral infection. Micro-ribonucleic acids (microRNAs) are small, non-coding RNA molecules that regulate gene expression by targeting complementary messenger RNA (mRNA) sequences. MicroRNAs can be packaged into extracellular vesicles (EVs), which are membrane-encapsulated vesicles released from host cells that play a role in cell-to-cell communication and regulation. This study focuses on investigating some aspects of the antiviral response against AIV and IBV infections in chickens, focusing on the role of microRNAs. The first two objectives focused on AIV H4N6 infection of chicken tracheal organ cultures (TOCs) to determine the profile of cellular and released EV microRNAs and evaluate the proteomic signature of EVs, as well as the function of EVs on chicken macrophages. The last two objectives explored infection with different strains of IBV in a chicken tracheal epithelial cell (cTEC) in vitro model and in the chicken trachea in vivo to characterize the mRNA and microRNA expression profiles. For the AIV experiments, we demonstrated for the first time that chicken tracheal cells secrete EVs. Differentially expressed (DE) microRNAs, such as miR-146a, miR-146b, miR-205a, miR-205b, and miR-449, were identified as potential targets for further functional validation studies. We determined that released EVs contain DE proteins involved in immune responses and cell signaling pathways and showed that these EVs can activate macrophages. For the IBV experiments, we showed that IBV Delmarva (DMV)/1639 and IBV Massachusetts (Mass)41 replicate in cTECs in vitro and the trachea in vivo, inducing host mRNA and microRNA expression profiles that are strain-, time-and model-dependent. We identified the candidate DE microRNAs, such as gga-miR-155, gga-miR-1388a, gga-miR-7/7b and gga-miR-21-5p. Overall, these findings provide valuable insights into key expression profiles and underlying mechanisms involved in the antiviral response against AIV and IBV infections in chickens.
dc.identifier.citationO'Dowd, K. (2024). Antiviral response against avian influenza virus and avian infectious bronchitis virus: focus on microRNA regulation (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.
dc.identifier.urihttps://hdl.handle.net/1880/118594
dc.identifier.urihttps://doi.org/10.11575/PRISM/43436
dc.language.isoen
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgary
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectavian influenza virus
dc.subjectavian infectious bronchitis virus
dc.subjectextracellular vesicles
dc.subjectmicroRNA
dc.subjectmRNA
dc.subjecttranscriptomics
dc.subjectproteomics
dc.subjecttracheal epithelial cells
dc.subjecttrachea
dc.subjectchicken
dc.subjectimmune response
dc.subject.classificationVeterinary Science
dc.subject.classificationImmunology
dc.subject.classificationVirology
dc.titleAntiviral Response Against Avian Influenza Virus and Avian Infectious Bronchitis Virus: Focus on MicroRNA Regulation
dc.typedoctoral thesis
thesis.degree.disciplineVeterinary Medical Sciences
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.thesis.accesssetbystudentI do not require a thesis withhold – my thesis will have open access and can be viewed and downloaded publicly as soon as possible.
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