title: Hepatitis B Virus Stimulated Fibronectin Facilitates Viral Maintenance and Replication through Two Distinct Mechanisms.
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.
authors.affiliation: The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Ren
authors.affiliation: Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China.
authors.forename: Tie-Long
authors.initials: TL
authors.lastname: Chen
authors.affiliation: The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Hao-Yu
authors.initials: HY
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Yu-Shun
authors.initials: YS
authors.lastname: Wan
authors.affiliation: The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Nan-Fang
authors.initials: NF
authors.lastname: Peng
authors.affiliation: Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China.
authors.forename: Xi-En
authors.initials: XE
authors.lastname: Gui
authors.affiliation: The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000328:Adult; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005260:Female; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000187:drug effects / Q000378:metabolism*; D019694:Hepatitis B, Chronic / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D005353:Fibronectins; D016898:Interferon-alpha; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D016329:Sp1 Transcription Factor; D000099151:MAP Kinase Kinase Kinase 7