Negative regulation of hepatitis B virus replication by cellular Hsp40/DnaJ proteins through destabilization of viral core and X proteins

• Published in: Journal of general virology 2006-07, Vol.87 (7), p.1883-1891
• Main Authors: Sohn, Sook-Young, Kim, Sun-Bum, Kim, Joon, Ahn, Byung-Yoon
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Biological and medical sciences; Cell Line, Tumor; Drosophila; Fundamental and applied biological sciences. Psychology; HeLa Cells; Hepatitis B virus; Hepatitis B virus - genetics; Hepatitis B virus - pathogenicity; Hepatitis B virus - physiology; HSP40 Heat-Shock Proteins - antagonists & inhibitors; HSP40 Heat-Shock Proteins - genetics; HSP40 Heat-Shock Proteins - physiology; HSP70 Heat-Shock Proteins - physiology; Humans; Microbiology; Miscellaneous; Proteasome Endopeptidase Complex - metabolism; Protein Binding; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; RNA Interference; RNA, Small Interfering - genetics; Trans-Activators; Transfection; Tumor Suppressor Proteins - antagonists & inhibitors; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - physiology; Two-Hybrid System Techniques; Viral Core Proteins - genetics; Viral Core Proteins - physiology; Viral Regulatory and Accessory Proteins - genetics; Viral Regulatory and Accessory Proteins - physiology; Virology; Virus Replication - physiology
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.81684-0

School of Life Sciences and Biotechnology, Korea University, Anamdong 5-1, Sungbuk, Seoul 136-701, Korea Correspondence Byung-Yoon Ahn ahnbyung{at}korea.ac.kr The hepatitis B virus core protein consists of an amino-terminal capsid-assembly domain and a carboxyl-terminal RNA-binding domain. By using the yeast two-hybrid system, two Hsp40/DnaJ chaperone-family proteins, Hdj1 and hTid1, that interact with the carboxyl-terminal region (aa 94–185) of the core protein were identified. Hdj1 is the prototype member of the family and hTid1 is the human homologue of the Drosophila tumour-suppressor protein Tid56. Binding of the viral core protein with the Hsp40 proteins was confirmed by affinity chromatography and immunoprecipitation of transiently expressed proteins. Moreover, in a sucrose gradient, the precursor form of hTid1 co-sedimented with capsid-like particles composed of the full-length core protein. Unlike the general perception of the role of the cellular chaperone proteins in assisting viral protein folding and thus enhancing virus replication, ectopic expression of Hdj1 and hTid1 suppressed replication of HBV in transfected human hepatoma cells. Conversely, RNA interference-mediated knock-down of hTid1 resulted in increased HBV replication. It was found that both Hsp40 proteins specifically accelerated degradation of the viral core and HBx proteins. Our results suggest that the cellular chaperones, through destabilization of viral proteins, exert inhibitory functions on virus replication and hence may play suppressive roles in hepatocellular carcinoma.