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Hepatitis C Virus Particle Assembly Involves Phosphorylation of NS5A by the c-Abl Tyrosine Kinase
- Source :
- The Journal of biological chemistry. 290(36)
- Publication Year :
- 2015
-
Abstract
- Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is thought to regulate the replication of viral RNA and the assembly of virus particles in a serine/threonine phosphorylation-dependent manner. However, the host kinases that phosphorylate NS5A have not been fully identified. Here, we show that HCV particle assembly involves the phosphorylation of NS5A by the c-Abl tyrosine kinase. Pharmacological inhibition or knockdown of c-Abl reduces the production of infectious HCV (J6/JFH1) particles in Huh-7.5 cells without markedly affecting viral RNA translation and replication. NS5A is tyrosine-phosphorylated in HCV-infected cells, and this phosphorylation is also reduced by the knockdown of c-Abl. Mutational analysis reveals that NS5A tyrosine phosphorylation is dependent, at least in part, on Tyr(330) (Tyr(2306) in polyprotein numbering). Mutation of this residue to phenylalanine reduces the production of infectious HCV particles but does not affect the replication of the JFH1 subgenomic replicon. These findings suggest that c-Abl promotes HCV particle assembly by phosphorylating NS5A at Tyr(330).
- Subjects :
- Hepatitis C virus
viruses
Immunoblotting
Hepacivirus
Biology
Viral Nonstructural Proteins
medicine.disease_cause
Biochemistry
Microbiology
Virus
chemistry.chemical_compound
Cell Line, Tumor
Chlorocebus aethiops
medicine
Animals
Humans
Phosphorylation
NS5A
Proto-Oncogene Proteins c-abl
Molecular Biology
Microscopy, Confocal
Kinase
Reverse Transcriptase Polymerase Chain Reaction
Virus Assembly
Virion
virus diseases
Tyrosine phosphorylation
Cell Biology
biochemical phenomena, metabolism, and nutrition
Molecular biology
digestive system diseases
NS2-3 protease
HEK293 Cells
chemistry
COS Cells
Host-Pathogen Interactions
RNA, Viral
Tyrosine
RNA Interference
Tyrosine kinase
Subjects
Details
- ISSN :
- 1083351X
- Volume :
- 290
- Issue :
- 36
- Database :
- OpenAIRE
- Journal :
- The Journal of biological chemistry
- Accession number :
- edsair.doi.dedup.....866c19efead483ca997c653b9b69aa57