title: Modulation of the type I interferon pathways by culture-adaptive hepatitis C virus core mutants.
abstract: Hepatitis C virus (HCV) often establishes a persistent infection that leads to chronic liver diseases. The viral core protein modulates various cellular activities involved in this process. We found two mutations, K23E and V31A, in the core gene of the transfected HCV JFH-1 genome, which had been replicated for a prolonged period. The mutant viruses escaped immunochemical detection by a core-specific antibody and demonstrated enhanced RNA replication and protein expression, compared to the parental virus. The mutant core proteins bound less tightly than the parental type core to the DEAD-box RNA helicase DDX3 and attenuated the TBK1-mediated activation of interferon-related promoters. These results suggest a mechanism by which the viruses adapt to attenuate cellular antiviral activity and to establish persistent infection.
authors.affiliation: School of Life Sciences & Biotechnology, Korea University, Republic of Korea.
authors.forename: Ju-Il
authors.initials: JI
authors.lastname: Kang
authors.forename: Young-Chan
authors.initials: YC
authors.lastname: Kwon
authors.forename: Byung-Yoon
authors.initials: BY
authors.lastname: Ahn
mesh_terms: D000222:Adaptation, Physiological; D000956:Antigens, Viral / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D046508:Culture Techniques; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D016679:Genome, Viral / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D009154:Mutation; D012367:RNA, Viral / Q000096:biosynthesis; D014758:Viral Core Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
chemical_list: D000956:Antigens, Viral; D007370:Interferon Type I; D012367:RNA, Viral; D014758:Viral Core Proteins; C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases