Negash, AA, Olson, RM, Griffin, S orcid.org/0000-0002-7233-5243 et al. (1 more author) (2019) Modulation of calcium signaling pathway by hepatitis C virus core protein stimulates NLRP3 inflammasome activation. PLoS pathogens, 15 (2). e1007593. ISSN 1553-7366
Abstract
Hepatitis C virus (HCV) infection remains a major cause of hepatic inflammation and liver disease. HCV triggers NLRP3 inflammasome activation and interleukin-1β (IL-1β) production from hepatic macrophages, or Kupffer cells, to drive the hepatic inflammatory response. Here we examined HCV activation of the NLRP3 inflammasome signaling cascade in primary human monocyte derived macrophages and THP-1 cell models of hepatic macrophages to define the HCV-specific agonist and cellular processes of inflammasome activation. We identified the HCV core protein as a virion-specific factor of inflammasome activation. The core protein was both necessary and sufficient for IL-1β production from macrophages exposed to HCV or soluble core protein alone. NLRP3 inflammasome activation by the HCV core protein required calcium mobilization linked with phospholipase-C activation. Our findings reveal a molecular basis of hepatic inflammasome activation and IL-1β release triggered by HCV core protein.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 Negash et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. (https://creativecommons.org/licenses/by/4.0/) |
Keywords: | Inflammasomes; Macrophages; Immune receptor signaling; Viral core; Hepatitis C virus; Virions; Enzyme-linked immunoassays; Calcium signaling |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Infection and Immunity (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 16 Apr 2019 11:26 |
Last Modified: | 25 Jun 2023 21:47 |
Status: | Published |
Publisher: | Public Library of Science |
Identification Number: | 10.1371/journal.ppat.1007593 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:145033 |