Startseite
English
Erweiterte Suche
Durchblättern nach ...
Publikationen im Überblick
Ansprechpartner
Hilfe
Verlagsversion
Postprint
DOI
 |
Open Access Gold |
|
möglich sobald bei der ZB eingereicht worden ist.
Hepatitis B virus activates signal transducer and activator of transcription 3 supporting hepatocyte survival and virus replication.
Cell. Mol. Gast. Hept. 4, 339-363 (2017)
Background & Aims The human hepatitis B virus (HBV) is a major cause of chronic hepatitis and hepatocellular carcinoma (HCC), but molecular mechanisms driving liver disease and carcinogenesis are largely unknown. We therefore studied cellular pathways altered by HBV infection. Methods We performed gene expression profiling of primary human hepatocytes (PHH) infected with HBV and proved the results in HBV-replicating cell lines and human liver tissue using real time PCR and Western blotting. Activation of signal transducer and activator of transcription (STAT3) was examined in HBV-replicating human hepatocytes, HBV-replicating mice and liver tissue from HBV-infected individuals using Western blotting, STAT3-luciferase reporter assay, and immunohistochemistry. The consequences of STAT3 activation on HBV infection and cell survival were studied by chemical inhibition of STAT3 phosphorylation and siRNA-mediated knockdown of STAT3. Results Gene expression profiling of HBV-infected PHH detected no interferon response, while genes encoding for acute phase and anti-apoptotic proteins were up-regulated. This gene regulation was confirmed in liver tissue samples of patients with chronic HBV infection and in HBV-related HCC. Pathway analysis revealed activation of STAT3 to be the major regulator. Interleukin-6-dependent and -independent activation of STAT3 was detected in HBV-replicating hepatocytes in cell culture and in vivo. Prevention of STAT3 activation by inhibition of Janus tyrosine kinases as well as siRNA-mediated knockdown of STAT3 induced apoptosis and reduced HBV replication and gene expression. Conclusions HBV activates STAT3 signaling in hepatocytes to foster its own replication but also to prevent apoptosis of infected cells. This very likely supports HBV-related carcinogenesis.
Altmetric
Weitere Metriken?
Zusatzinfos bearbeiten
[➜Einloggen]
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
hepatitis B virus infection, STAT3 signaling, hepatocellular carcinoma, apoptosis
ISSN (print) / ISBN
2352-345X
e-ISSN
2352-345X
Quellenangaben
Band: 4,
Heft: 3,
Seiten: 339-363
Verlag
Elsevier
Verlagsort
New York, NY
Nichtpatentliteratur
Publikationen
Institut(e)
Institute of Virology (VIRO)