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Involvement of Creatine Kinase B in Hepatitis C Virus Genome Replication through Interaction with the Viral NS4A Protein
- Source :
- Journal of Virology. 83:5137-5147
- Publication Year :
- 2009
- Publisher :
- American Society for Microbiology, 2009.
-
Abstract
- Persistent infection with hepatitis C virus (HCV) is a major cause of chronic liver diseases. The aim of this study was to identify host cell factor(s) participating in the HCV replication complex (RC) and to clarify the regulatory mechanisms of viral genome replication dependent on the host-derived factor(s) identified. By comparative proteome analysis of RC-rich membrane fractions and subsequent gene silencing mediated by RNA interference, we identified several candidates for RC components involved in HCV replication. We found that one of these candidates, creatine kinase B (CKB), a key ATP-generating enzyme that regulates ATP in subcellular compartments of nonmuscle cells, is important for efficient replication of the HCV genome and propagation of infectious virus. CKB interacts with HCV NS4A protein and forms a complex with NS3-4A, which possesses multiple enzyme activities. CKB upregulates both NS3-4A-mediated unwinding of RNA and DNA in vitro and replicase activity in permeabilized HCV replicating cells. Our results support a model in which recruitment of CKB to the HCV RC compartment, which has high and fluctuating energy demands, through its interaction with NS4A is important for efficient replication of the viral genome. The CKB-NS4A association is a potential target for the development of a new type of antiviral therapeutic strategy.
- Subjects :
- Gene Expression Regulation, Viral
Proteomics
viruses
Hepatitis C virus
Immunology
RNA-dependent RNA polymerase
Genome, Viral
Hepacivirus
Viral Nonstructural Proteins
Biology
Virus Replication
medicine.disease_cause
Microbiology
Virus
Viral Proteins
Adenosine Triphosphate
Replication factor C
RNA interference
Cell Line, Tumor
Virology
Creatine Kinase, BB Form
medicine
Humans
Intracellular Signaling Peptides and Proteins
virus diseases
Hepatitis C
Virus-Cell Interactions
NS2-3 protease
Viral replication
Insect Science
RNA, Viral
RNA Interference
Carrier Proteins
Viral genome replication
Subjects
Details
- ISSN :
- 10985514 and 0022538X
- Volume :
- 83
- Database :
- OpenAIRE
- Journal :
- Journal of Virology
- Accession number :
- edsair.doi.dedup.....314edaddc7228012225e80547a26494a