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Natural killer cells inhibit hepatitis C virus expression
Author(s) -
Li Yuan,
Zhang Ting,
Ho Chun,
Orange Jordan S.,
Douglas Steven D.,
Ho WenZhe
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0604372
Subject(s) - biology , interleukin 21 , nk 92 , cd49b , janus kinase 3 , interleukin 12 , lymphokine activated killer cell , interferon , natural killer cell , hepatitis c virus , stat protein , cell culture , nkg2d , immunology , microbiology and biotechnology , virus , signal transduction , cytotoxic t cell , immune system , t cell , stat3 , in vitro , biochemistry , genetics
Natural killer (NK) cells are critical in host innate defense against certain viruses. The role of NK cells in controlling hepatitis C virus (HCV) remains obscure. We examined whether NK cells are capable of inhibiting HCV expression in human hepatic cells. When NK cells are cultured with the HCV replicon‐containing hepatic cells, they have no direct cytolytic effect but release soluble factor(s) suppressing HCV RNA expression. Media conditioned by NK cell lines (NK‐92 and YTS) or primary NK cells isolated from healthy donors contain interferon γ (IFN‐γ) and potently inhibit HCV RNA expression. Ligation of CD81 on NK cells inhibits IFN‐γ production and results in decreased anti‐HCV activity. In addition, the antibodies to IFN‐γ or IFN‐γ receptors abolish the anti‐HCV activity of NK cell‐conditioned media. The role of IFN‐γ in NK cell‐mediated, anti‐HCV activity is supported by the observation that NK cell‐conditioned media enhanced expression of signal transducer and activator of transcription‐1, a nuclear factor that is essential in IFN‐γ‐mediated antiviral pathways. NK cell‐conditioned media have the ability to stimulate intracellular IFN‐α expression in the hepatic cells, suggesting a mechanism responsible for NK cell‐mediated, anti‐HCV activity. Thus, NK cells hold the potential to play a vital role in controlling HCV replication in hepatic cells using an IFN‐γ‐dependent mechanism.