2015
DOI: 10.1128/jvi.02440-14
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The Hepatitis B Virus (HBV) HBx Protein Activates AKT To Simultaneously Regulate HBV Replication and Hepatocyte Survival

Abstract: Chronic infection with hepatitis B virus (HBV) is a risk factor for developing liver diseases such as hepatocellular carcinoma (HCC). HBx is a multifunctional protein encoded by the HBV genome; HBx stimulates HBV replication and is thought to play an important role in the development of HBV-associated HCC. HBx can activate the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway in some cell lines; however, whether HBx regulates PI3K/AKT signaling in normal hepatocytes has not been evaluated. In studies … Show more

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Cited by 114 publications
(147 citation statements)
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References 91 publications
(157 reference statements)
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“…The HBx protein is an important oncoprotein in HCC pathogenesis33, and mutations in this region may alter its biological functions, thereby increasing its oncogenicity. Moreover, pAKT levels and TACO may exert synergistic instead of additive effects on HCC survival because the HBx protein can activate AKT to regulate hepatocyte survival31. However, this synergistic effect does not seem to apply to our study because we found a discrepancy in the levels of SKP2 mRNA produced by HCC expressing high levels of pAKT and TACO.…”
Section: Discussionmentioning
confidence: 72%
See 1 more Smart Citation
“…The HBx protein is an important oncoprotein in HCC pathogenesis33, and mutations in this region may alter its biological functions, thereby increasing its oncogenicity. Moreover, pAKT levels and TACO may exert synergistic instead of additive effects on HCC survival because the HBx protein can activate AKT to regulate hepatocyte survival31. However, this synergistic effect does not seem to apply to our study because we found a discrepancy in the levels of SKP2 mRNA produced by HCC expressing high levels of pAKT and TACO.…”
Section: Discussionmentioning
confidence: 72%
“…Specifically, cell- and animal-based experiments show that AKT1 interacts with several HBV proteins to contribute to deterioration in liver disease31. Moreover, some studies illustrate that HBV mutations are closely associated with HCC development and tumour progression1516.…”
Section: Discussionmentioning
confidence: 99%
“…Literature suggests that the PI 3-kinase/Akt signaling pathway plays an important role in cell survival in liver (Jiang et al, 2014; Rawat and Bouchard, 2015; Saha et al, 2016). …”
Section: Resultsmentioning
confidence: 99%
“…At the early stage of HBV infection, HBx activates AKT and inhibits apoptosis. The balance between virus replication and cell survival may cause the failure to remove infected cells and benefit persistent HBV infection 42,43. At the late stages of HBV infection, HBx becomes more proapoptotic and may accelerate HBV-induced liver damage.…”
Section: Hepatocyte Apoptosis and Viral Hepatitismentioning
confidence: 99%