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Cochaperone Activity of Human Butyrate-Induced Transcript 1 Facilitates Hepatitis C Virus Replication through an Hsp90-Dependent Pathway
- Source :
- Journal of Virology. 83:10427-10436
- Publication Year :
- 2009
- Publisher :
- American Society for Microbiology, 2009.
-
Abstract
- Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a component of the replication complex consisting of several host and viral proteins. We have previously reported that human butyrate-induced transcript 1 (hB-ind1) recruits heat shock protein 90 (Hsp90) and FK506-binding protein 8 (FKBP8) to the replication complex through interaction with NS5A. To gain more insights into the biological functions of hB-ind1 in HCV replication, we assessed the potential cochaperone-like activity of hB-ind1, because it has significant homology with cochaperone p23, which regulates Hsp90 chaperone activity. The chimeric p23 in which the cochaperone domain was replaced with the p23-like domain of hB-ind1 exhibited cochaperone activity comparable to that of the authentic p23, inhibiting the glucocorticoid receptor signaling in an Hsp90-dependent manner. Conversely, the chimeric hB-ind1 in which the p23-like domain was replaced with the cochaperone domain of p23 resulted in the same level of recovery of HCV propagation as seen in the authentic hB-ind1 in cells with knockdown of the endogenous hB-ind1. Immunofluorescence analyses revealed that hB-ind1 was colocalized with NS5A, FKBP8, and double-stranded RNA in the HCV replicon cells. HCV replicon cells exhibited a more potent unfolded-protein response (UPR) than the parental and the cured cells upon treatment with an inhibitor for Hsp90. These results suggest that an Hsp90-dependent chaperone pathway incorporating hB-ind1 is involved in protein folding in the membranous web for the circumvention of the UPR and that it facilitates HCV replication.
- Subjects :
- Protein Folding
Immunology
Hepacivirus
Kidney
Virus Replication
Microbiology
Cell Line
Cell Line, Tumor
Virology
Heat shock protein
Humans
HSP90 Heat-Shock Proteins
NS5A
Gene
Hydro-Lyases
Messenger RNA
Gene knockdown
biology
Intracellular Signaling Peptides and Proteins
RNA
Molecular biology
Hsp90
Virus-Cell Interactions
Gene Expression Regulation
Liver
Insect Science
Chaperone (protein)
biology.protein
Molecular Chaperones
Subjects
Details
- ISSN :
- 10985514 and 0022538X
- Volume :
- 83
- Database :
- OpenAIRE
- Journal :
- Journal of Virology
- Accession number :
- edsair.doi.dedup.....a4942a0aef643e530002927320201c13