Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6138482 | Virology | 2016 | 14 Pages |
Abstract
Chronic HBV infection is a risk factor for hepatocellular carcinoma (HCC). The HBV HBx protein stimulates HBV replication and likely influences the development of HBV-associated HCC. Whether HBx affects regulators of metabolism in normal hepatocytes has not been addressed. We used an ex vivo, cultured primary rat hepatocyte system to assess the interplay between HBV replication and mechanistic target of rapamycin complex 1 (mTORC1) signaling. HBx activated mTORC1 signaling; however, inhibition of mTORC1 enhanced HBV replication. HBx also decreased ATP levels and activated the energy-sensing factor AMP-activated protein kinase (AMPK). Inhibition of AMPK decreased HBV replication. Inhibition of AMPK activates mTORC1, and we showed that activated mTORC1 is one factor that reduces HBV replication when AMPK is inhibited. HBx activation of both AMPK and mTORC1 suggests that these activities could provide a balancing mechanism to facilitate persistent HBV replication. HBx activation of mTORC1 and AMPK could also influence HCC development.
Keywords
AMPKProtein kinase C ζPKCζp70 S6 kinaseS6KTSC2eukaryotic translation initiation factor 4E binding protein 1HBV X proteincccDNAHBxmTORC14EBP1TBSTGFPORFLKB1PBSSDSITSEGFACCPVDFAMP-activated protein kinasecovalently closed circular DNAHCCacetyl-CoA carboxylaseinsulin-transferrin-seleniumViral replicationpolyvinylidene difluoridesodium dodecyl sulfateepidermal growth factoropen reading frameMetabolismPhosphate-buffered salinePrimary hepatocyteHBVViruseshepatitis B virusgreen fluorescent proteinHepatocellular carcinomaliver kinase B1
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Authors
Sumedha Bagga, Siddhartha Rawat, Marcia Ajenjo, Michael J. Bouchard,