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

Sook Young Sohn, Sun Bum Kim, Joon Kim, Byung-Yoon Ahn

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1883-1891
Number of pages9
JournalJournal of General Virology
Volume87
Issue number7
DOIs
Publication statusPublished - 2006 Jul 1

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HSP40 Heat-Shock Proteins
Viral Core Proteins
Virus Replication
Hepatitis B virus
Proteins
Capsid
Viral Proteins
Hepatocellular Carcinoma
Tumor Suppressor Proteins
Drosophila Proteins
Two-Hybrid System Techniques
Protein Folding
RNA Interference
Affinity Chromatography
Immunoprecipitation
Sucrose

ASJC Scopus subject areas

  • Virology
  • Immunology

Cite this

Negative regulation of hepatitis B virus replication by cellular Hsp40/DnaJ proteins through destabilization of viral core and X proteins. / Sohn, Sook Young; Kim, Sun Bum; Kim, Joon; Ahn, Byung-Yoon.

In: Journal of General Virology, Vol. 87, No. 7, 01.07.2006, p. 1883-1891.

Research output: Contribution to journalArticle

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