Browsing by Author "O'Dowd, Kelsey"

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    Antiviral Response Against Avian Influenza Virus and Avian Infectious Bronchitis Virus: Focus on MicroRNA Regulation
    (2024-04-29) O'Dowd, Kelsey; Abdul-Careem, Mohamed Faizal; Gagnon, Carl A.; van der Meer, Franciscus Johannes; Niu, Dongyan Xu; Niikura, Masahiro; Susta, Leonardo
    Avian 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.