Modulation of calcium signaling pathway by hepatitis C virus core protein stimulates NLRP3 inflammasome activation

PLoS Pathogens
Amina A NegashMichael Gale

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.

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Citations

May 27, 2020·Journal of Cellular Physiology·Xiao-Qin LuoCha-Xiang Guan
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Datasets Mentioned

BETA
DQ849011.1

Methods Mentioned

BETA
ELISA
PMA
transfection
in vitro transcription
immunoprecipitation
Co-IP

Software Mentioned

NIS
IncuCyte

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