title: Natural killer cells target HCV core proteins during the innate immune response in HCV transgenic mice.
abstract: The mechanism of the innate immune response to hepatitis C virus (HCV) has not been fully elucidated, largely due to the lack of an appropriate model. We used HCV transgenic (Tg) mice, which express core, E1, E2, and NS2 proteins regulated by the Cre/loxP switching expression system, to examine the innate immune response to HCV structural proteins. Twelve hours after HCV transgene expression, HCV core protein levels in Tg mouse livers were 15-47 pg/mg. In contrast, in Tg mice with a depletion of natural killer (NK) cells, we observed much higher levels of HCV core proteins (1,597 pg/ml). Cre-mediated genomic DNA recombination efficiency in the HCV-Tg mice was strongly observed in NK cell-depleted mice between 0.5 and 1 day as compared to non-treated mice. These data indicated that NK cells participate in the elimination of core-expressing hepatocytes in the innate immune responses during the acute phase of HCV infection.
authors.affiliation: Department of Microbiology and Cell Biology, The Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 156-8506, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Satoh
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Chiho
authors.initials: C
authors.lastname: Matsuda
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyasaka
authors.forename: Mikio
authors.initials: M
authors.lastname: Zeniya
authors.forename: Michinori
authors.initials: M
authors.lastname: Kohara
mesh_terms: D000818:Animals; D003602:Cytotoxicity, Immunologic; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000473:pathology / Q000821:virology; D022781:Hepatocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology*; D008099:Liver / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D014758:Viral Core Proteins / Q000276:immunology* / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000276:immunology
chemical_list: C087035:E1 protein, Hepatitis C virus; C097010:NS2 protein, Hepatitis C virus; D014758:Viral Core Proteins; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; C069130:nucleocapsid protein, Hepatitis C virus; C091015:glycoprotein E2, Hepatitis C virus