Characterization of the Antiviral Functions of Interleukin-27 during Dengue Virus Infection of Human Macrophages
Loading...
Authors
Roth, Madison
Date
Type
thesis
Language
eng
Keyword
Dengue virus , IL-27 , Macrophages
Alternative Title
Abstract
Dengue virus (DENV) causes the most prevalent mosquito-transmitted viral disease, including dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), with an estimated 390 million infections and 20,000 deaths annually. DENV is an arbovirus transmitted by Aedes mosquitoes, which are expanding into new regions of the world as a result of societal and environmental changes; therefore, DENV is emerging as a significant global health threat. Despite its growing relevance, there are still no widely used vaccines or effective antiviral therapies available for DENV. Recent investigations have uncovered that the cytokine interleukin 27 (IL-27) displays antiviral properties against human immunodeficiency virus (HIV), influenza A virus (IAV), hepatitis B virus (HBV), hepatitis C virus (HCV), and Zika virus (ZIKV). Furthermore, IL-27 has been previously shown to regulate the function of monocytes and macrophages, which are the primary cells infected by DENV. However, the role of IL-27 in innate antiviral immune responses against DENV infection and pathogenesis has not been investigated. Therefore, to address this knowledge gap, we set out to determine if: 1) DENV infection of THP-1-derived human macrophages could induce IL-27 expression and 2) if IL-27 could modulate DENV replication in human macrophages. Here, we show that infection of phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 cells with DENV-2 (strain 16881) resulted in significant induction of IL-27 production. Treatment of uninfected or infected THP-1 macrophages with recombinant human IL-27 (rhIL-27) induced expression of antiviral interferon-stimulated genes (ISGs), such as myxovirus resistance protein 1 (MX1). Furthermore, IL-27 dose-dependently inhibited DENV infection in PMA-differentiated THP-1 macrophages in a manner partially dependent on type I interferons (IFNs). These results identify a role for IL-27 in innate immune defense against DENV infection, potentiating its use as an antiviral agent.
Description
Citation
Publisher
License
Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
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.
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.