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Regulation of hepatitis B virus replication by the phosphatidylinositol 3-kinase-akt signal transduction pathway
Journal article   Open access   Peer reviewed

Regulation of hepatitis B virus replication by the phosphatidylinositol 3-kinase-akt signal transduction pathway

Haitao Guo, Tianlun Zhou, Dong Jiang, Andrea Cuconati, Guang-Hui Xiao, Timothy M Block and Ju-Tao Guo
Journal of virology, v 81(18), pp 10072-10080
Sep 2007
DOI: https://doi.org/10.1128/JVI.00541-07
PMID: 17609269
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1128/jvi.00541-07View
Published, Version of Record (VoR),  Open
url
https://doi.org/10.1128/JVI.00541-07View
Published, Version of Record (VoR) Open

Abstract

Carcinoma, Hepatocellular - metabolism Carcinoma, Hepatocellular - virology Cell Line, Tumor Cell Transformation, Viral - drug effects Cell Transformation, Viral - physiology DNA Replication - drug effects DNA, Viral - metabolism Hepacivirus - metabolism Hepatitis B - complications Hepatitis B - metabolism Hepatitis B virus - metabolism Hepatitis C - complications Hepatitis C - metabolism Humans Immunosuppressive Agents - pharmacology Phosphatidylinositol 3-Kinases - metabolism Protein Kinases - metabolism Proto-Oncogene Proteins c-akt - metabolism RNA, Viral - metabolism Signal Transduction Sirolimus - pharmacology TOR Serine-Threonine Kinases Transcription, Genetic - drug effects Viral Nonstructural Proteins - metabolism Virus Replication - drug effects Virus Replication - physiology
The phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway is one of the major oncogenic pathways and is activated in many types of human cancers, including hepatocellular carcinoma. It can also be activated by the hepatitis C virus (HCV) nonstructural 5A (NS5A) protein. In the present study, we set out to determine the regulatory effects of this pathway on the replication of hepatitis B virus (HBV). Our results demonstrate that the expression of a constitutively active Akt1 profoundly inhibited HBV RNA transcription and consequently reduced HBV DNA replication in HepG2 cells. This suppression of HBV gene transcription was apparently mediated by the activation of mTOR, as it was abolished by the mTOR inhibitor rapamycin. Moreover, treatment of HBV-expressing HepG2.2.15 cells with inhibitors of PI3K, Akt, and mTOR increased the transcription of 3.5-kb and 2.4-kb viral RNA as well as the replication of HBV DNA. This observation implies that the basal level activation of this pathway in HepG2 cells regulated HBV replication. Consistent with previous reports showing that the HCV NS5A protein could bind to the p85 subunit of PI3K and activate the PI3K-Akt signal transduction pathway, our results showed that expression of this protein could inhibit HBV RNA transcription and reduce HBV DNA replication in HepG2 cells. Taken together, our results suggest that the activation of the PI3K-Akt pathway during liver oncogenesis may be at least partially responsible for the elimination of HBV replication from tumor cells and may also provide an explanation for the observed suppression of HBV replication by HCV coinfection.

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Collaboration types
Domestic collaboration
Web of Science research areas
Virology
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