Research Papers: Immunology:
HCV core protein binds to gC1qR to induce A20 expression and inhibit cytokine production through MAPKs and NF-κB signaling pathways
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Xiaotian Song1,2,*, Zhiyan Yao1,2,*, Jianling Yang1,2, Zhengzheng Zhang1,2, Yuqing Deng1,2, Miao Li1,2, Cuiqing Ma1,2, Lijuan Yang1,2, Xue Gao1,2, Wenjian Li1,2, Jianguo Liu3 and Lin Wei1,2
1 Department of Immunology, Hebei Medical University, Shijiazhuang, China
2 Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, China
3 Division of Infectious Diseases, Allergy and Immunology, Departments of Internal Medicine and Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, USA
* These authors have contributed equally to this work
Lin Wei, email:
Keywords: hepatitis C virus, core protein, macrophage, negative regulator A20, gC1qR, Immunology and Microbiology Section, Immune response, Immunity
Received: January 05, 2016 Accepted: April 25, 2016 Published: May 11, 2016
Hepatitis C virus (HCV) infection is characterized by a strong propensity toward chronicity. During chronic HCV infection, HCV core protein is implicated in deregulating cytokine expression that associates with chronic inflammation. A20 is known as a powerful suppressor in cytokine signaling, in this study, we explored the A20 expression in macrophages induced by HCV core protein and the involved signaling pathways. Results demonstrated that HCV core protein induced A20 expression in macrophages. Silencing A20 significantly enhanced the secretion of IL-6, IL-1β and TGF-β1, but not IL-8 and TNF. Additionally, HCV core protein interacted with gC1qR, but not TLR2, TLR3 and TLR4 in pull-down assay. Silencing gC1qR abrogated core-induced A20 expression. Furthermore, HCV core protein activated MAPK, NF-κB and PI3K/AKT pathways in macrophages. Inhibition of P38, JNK and NF-κB but not ERK and AKT activities greatly reduced the A20 expression. In conclusion, the study suggests that HCV core protein ligates gC1qR to induce A20 expression in macrophages via P38, JNK and NF-κB signaling pathways, which leads to a low-grade chronic inflammation during HCV infection. It represents a novel mechanism by which HCV usurps the host for persistence.
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