title: Casein kinase II inhibitor enhances production of infectious genotype 1a hepatitis C virus (H77S).
abstract: Genotype 2a JFH1 virus has substantially contributed to the progress of HCV biology by allowing entire viral life cycle of HCV in cell culture. Using this genotype 2a virus, casein kinase II (CKII) was previously identified as a crucial host factor in virus assembly by phosphorylating NS5A. Since most of the prior studies employed genotype 2a JFH1 or JFH1-based intragenotypic chimera, we used genotype 1a H77S to study virus assembly. CKII inhibition by chemical inhibitors enhanced H77S virus production in contrast to that of JFH1 virus, but genetic inhibition of CKII by siRNA did not change H77S virus titer significantly. The different outcomes from these two approaches of CKII inhibition suggested that nonspecific target kinase of CKII inhibitors plays a role in increasing H77S virus production and both viral and host factors were investigated in this study. Our results emphasize substantial differences among the HCV genotypes that should be considered in both basic research and clinical practices.
authors.affiliation: Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea; Institute of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Seungtaek
authors.initials: S
authors.lastname: Kim
authors.affiliation: Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Bora
authors.initials: B
authors.lastname: Jin
authors.affiliation: Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea; Institute of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Kwang-Hyub
authors.initials: KH
authors.lastname: Han
authors.affiliation: Institute of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Ahn
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D002460:Cell Line; D002934:Cinnamates / Q000494:pharmacology; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D008969:Molecular Sequence Data; D034622:RNA Interference; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D047390:Casein Kinase II; D002934:Cinnamates; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; C492322:2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole; C518786:tetrabromocinnamic acid; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase