Regulation of Molecular Chaperone GRP78 by Hepatitis B Virus: Control of Viral Replication and Cell Survival
| Autor: | Zhiwei Guo, Lijie Li, Wangqin Shu, Ruijie Gong, Yuanyuan Yang, Yuqi Li, Ziyu Wang, Zhiqi Xiong, Minjing He, Bo Gao |
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| Rok vydání: | 2020 |
| Předmět: |
Hepatitis B virus
Cirrhosis Regulator Biology Virus Replication medicine.disease_cause Cell Line 03 medical and health sciences 0302 clinical medicine medicine Humans Endoplasmic Reticulum Chaperone BiP Molecular Biology Protein kinase B Heat-Shock Proteins 030304 developmental biology 0303 health sciences TOR Serine-Threonine Kinases Endoplasmic reticulum Cell Biology Endoplasmic Reticulum Stress Hepatitis B medicine.disease digestive system diseases Viral replication 030220 oncology & carcinogenesis Hepatocellular carcinoma Hepatocytes Unfolded protein response Cancer research Proto-Oncogene Proteins c-akt Signal Transduction Research Article |
| Zdroj: | Mol Cell Biol |
| ISSN: | 1098-5549 |
| Popis: | Chronic hepatitis B (CHB) remains a global health problem, carrying a high risk for progression into cirrhosis and liver failure. Molecular chaperones are involved in diverse pathophysiological processes including viral infection. However, the role of molecular chaperones in hepatitis B virus (HBV) infection and its underlying mechanisms remain unclear. Here, we identified GRP78 as one of the molecular chaperones most strongly induced by HBV in human hepatocytes. Gain- and loss-of-function analyses demonstrated that GRP78 exerted an inhibitory effect on HBV transcription and replication. Further study showed that GRP78 was involved in the activation of AKT/mTOR signaling in hepatocytes, which contributed to GRP78-mediated inhibition of HBV. Of note, HBV-upregulated GRP78 was found to play a crucial role in maintaining the survival of hepatocytes via facilitating a mild endoplasmic reticulum (ER) stress. Together, our findings suggest that HBV may sacrifice part of its replication for establishing a persistent infection through induction of GRP78, a master ER stress regulator. Targeting GRP78 may help develop to design novel therapeutic strategies against chronic HBV infection and the associated hepatocellular carcinoma. |
| Databáze: | OpenAIRE |
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