A promising alternative anti-HBV agent: The targeted ribonuclease
HBV-targeted ribonuclease (TR) is a fusion of HBV core protein (HBVc) and human eosinophil-derived neurotoxin (hEDN). Introduction of TR by transfection or transduction into HepG2.2.15 cells (a cell model of HBV infection) revealed that it significantly reduces serological markers of HBV replication (including HBsAg, HBeAg and HBV DNA) in cell supernatants, suggesting that the targeted ribonuclease inhibits HBV replication. To further our understanding of the molecular mechanism of the anti-HBV effect of TR, we expressed TR in E. coli and found that purified TR possesses RNase activity and targeting activity. Furthermore, the antiviral effect of TR depends both on an enzymatically active hEDN and on the core domain. In or out of HepG2.2.15 cells, TR coassembles with the wild-type capsid protein into particles with internal hEDN domains. Our data suggest an intracellular ribonuclease activation mechanism that, owing to the characteristics of HBV morphogenesis, is highly virus specific. HBV may therefore be particularly vulnerable to the capsid-targeted viral inactivation approach.
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Document Type: Research Article
Affiliations: Department of Medical Microbiology and Parasitology, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
Publication date: July 1, 2010
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- The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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