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PLoS One. 2016 Jul 19;11(7):e0159089. doi: 10.1371/journal.pone.0159089. eCollection 2016.

Hepatitis B Virus Middle Protein Enhances IL-6 Production via p38 MAPK/NF-κB Pathways in an ER Stress-Dependent Manner.

Li YX1,2,3, Ren YL1,2,3, Fu HJ1,2,3, Zou L1,2,3, Yang Y1,2, Chen Z1,2,3.

Author information

1
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Institute of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
2
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
3
School of Medicine, Zhejiang University, Hangzhou, China.

Abstract

During hepatitis B virus (HBV) infection, three viral envelope proteins of HBV are overexpressed in the endoplasmic reticulum (ER). The large S protein (LHBs) and truncated middle S protein (MHBst) have been documented to play roles in regulating host gene expression and contribute to hepatic disease development. As a predominant protein at the ultrastructural level in biopsy samples taken from viremic patients, the role of the middle S protein (MHBs) remains to be understood despite its high immunogenicity. When we transfected hepatocytes with an enhanced green fluorescent protein (EGFP)-tagged MHBs expressing plasmid, the results showed that expression of MHBs cause an upregulation of IL-6 at the message RNA and protein levels through activating the p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-kappa B (NF-κB) pathways. The use of specific inhibitors of the signaling pathways can diminish this upregulation. The use of BAPTA-AM attenuated the stimulation caused by MHBs. We further found that MHBs accumulated in the endoplasmic reticulum and increased the amount of glucose regulated protein 78 (GRP78/BiP). Our results provide a possibility that MHBs could be involved in liver disease progression.

PMID:
27434097
PMCID:
PMC4951109
DOI:
10.1371/journal.pone.0159089
[Indexed for MEDLINE]
Free PMC Article

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