Natural killer cells target HCV core proteins during the innate immune response in HCV transgenic mice.
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.
Satoh
Kenichi
K
Department of Microbiology and Cell Biology, The Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 156-8506, Japan.
Takahashi
Hiroki
H
Matsuda
Chiho
C
Tanaka
Toshiyuki
T
Miyasaka
Masayuki
M
Zeniya
Mikio
M
Kohara
Michinori
M
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
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