Hepatitis B virus stimulated fibronectin facilitates viral maintenance and replication through two distinct mechanisms

Sheng Ren, Jun Wang, Tie Long Chen, Hao Yu Li, Yu Shun Wan, Nan Fang Peng, Xi En Gui, Ying Zhu

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Fibronectin (FN) is a high molecular weight extracellular matrix protein that functions in cell adhesion, growth, migration, and embryonic development. However, little is known about the role of FN during viral infection. In the present study, we found significantly higher levels of FN in sera, and liver tissues from hepatitis B virus (HBV) patients relative to healthy individuals. HBV expression enhanced FN mRNA and protein levels in the hepatic cell lines Huh7 and HepG2. HBV infection of susceptible HepG2-sodium taurocholate co-transporting polypeptide cells also increased FN expression. We also found that transcriptional factor specificity protein 1 was involved in the induction of FN by HBV. Knockdown of FN expression significantly inhibited HBV DNA replication and protein synthesis through activating endogenous IFN-α production. In addition, FN interacted with the transforming growth factor β-activated protein kinase 1 (TAK1) and TAK1-binding protein complex and attenuated interferon signaling by inhibiting TAK1 phosphorylation. Furthermore, the nuclear translocation of NF-κB/p65 was found to be inhibited by FN. We also observed that FN promoted HBV enhancers to support HBV expression. These results suggest novel functions of endogenous FN involved in immune evasion and maintenance of HBV replication.

Original languageEnglish (US)
Article numbere0152721
JournalPloS one
Volume11
Issue number3
DOIs
StatePublished - Mar 2016

Bibliographical note

Funding Information:
This work was supported by research grants from the Major State Basic Research Development Program of China (2013CB911102), National Natural Science Foundation of China (81461130019, 81271821 and 31570870), National Mega Project on Major Infectious Diseases Prevention (2012ZX10004503-004). The funding agencies had no role in study design, data collection, or analysis, decision to publish, or preparation of the manuscript.

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