Interleukin-27 Inhibition of Pandemic Influenza A Virus Infection in Human Macrophages Partially Relies on Type I IFNs.
Authors
Amsden, Heather
Date
Type
thesis
Language
eng
Keyword
Interleukin-27 , Influenza , Interferons , Viral immunology , Infection , Antiviral immunity
Alternative Title
Abstract
Zoonotic reservoirs as well as high mutation rates make influenza A viruses (IAV) a looming pandemic threat. Recent studies have identified antiviral activities of the cytokine interleukin-27 (IL-27) against several viruses, including seasonal IAV. However, the role of IL-27 during infection with pandemic IAV strains is currently unknown. Here, we demonstrated that IL-27 inhibited pandemic IAV infection (A/New York/18/2009) by type I interferon (IFN)-dependent and -independent pathways. Using THP-1-derived human macrophages, IL-27 treatment was found to dose-dependently inhibit pandemic IAV infection, and this inhibition was associated with increased expression of antiviral genes, such as myxovirus resistance 1 (MX1), radical S-adenosyl methionine domain containing 2 (RSAD2), interferon induced transmembrane protein 3 (IFITM3) and interferon regulatory factor 1 (IRF1). IL-27-mediated upregulation of these antiviral genes was partly reliant on type I IFNs; MX1 and RSAD2 expression was type I IFN-dependent, IFITM3 expression was both type I IFN-dependent and independent, and IRF1 expression was type I IFN-independent. Accordingly, IL-27 inhibition of pandemic IAV infection was reduced, but not completely abrogated, in the absence of type I IFN signaling. Furthermore, IL-27 treatment promoted the production of chemokines important for recruitment of leukocytes, particularly CXCL9 and CXCL10. These findings identify a potential protective role of IL-27 in innate immune responses to pandemic IAV infection and highlight the antiviral therapeutic potential of IL-27.
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ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.