HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print August 31, 2004

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.0604372v1 76/6/1171    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, Y. Articles by Ho, W.-Z. Search for Related Content PubMed PubMed Citation Articles by Li, Y. Articles by Ho, W.-Z.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0604372

Received for publication June 29, 2004.
Revised August 6, 2004.
Accepted for publication August 10, 2004.

Article

Natural killer cells inhibit hepatitis C virus expression

Division of Allergy & Immunology, Joseph Stokes Jr. Research Institute at The Children’s Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine

^@ To whom correspondence should be addressed. E-mail: ho{at}email.chop.edu.

	Abstract

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 (IFN-) and potently inhibit HCV RNA expression. Ligation of CD81 on NK cells inhibits IFN- production and results in decreased anti-HCV activity. In addition, antibodies to IFN- or IFN- receptors abolish the anti-HCV activity of NK cell-conditioned media. The role of IFN- in NK cell-mediated, anti-HCV activity is supported by enhanced expression of signal transducer and activator of transcription-1, a nuclear factor that is essential in IFN--mediated antiviral pathways, by NK cell-conditioned media, which have the ability to stimulate intracellular IFN- expression in the hepatic cells, suggesting a mechanism responsible for NK cell-mediated, anti-HCV activity in the hepatic cells. Thus, NK cells hold the potential to play a vital role in controlling HCV replication in hepatic cells using an IFN--dependent mechanism.

Key Words: interferon • CD81 • STAT

This article has been cited by other articles:

				P. P. Banerjee, R. Pandey, R. Zheng, M. M. Suhoski, L. Monaco-Shawver, and J. S. Orange Cdc42-interacting protein 4 functionally links actin and microtubule networks at the cytolytic NK cell immunological synapse J. Exp. Med., October 1, 2007; 204(10): 2305 - 2320. [Abstract] [Full Text] [PDF]

				L. Golden-Mason, N. Castelblanco, C. O'Farrelly, and H. R. Rosen Phenotypic and Functional Changes of Cytotoxic CD56pos Natural T Cells Determine Outcome of Acute Hepatitis C Virus Infection J. Virol., September 1, 2007; 81(17): 9292 - 9298. [Abstract] [Full Text] [PDF]

				M. P. Windisch, M. Frese, A. Kaul, M. Trippler, V. Lohmann, and R. Bartenschlager Dissecting the Interferon-Induced Inhibition of Hepatitis C Virus Replication by Using a Novel Host Cell Line J. Virol., November 1, 2005; 79(21): 13778 - 13793. [Abstract] [Full Text] [PDF]

				A. P. Williams, A. R. Bateman, and S. I. Khakoo HANGING IN THE BALANCE: KIR and Their Role in Disease Mol. Interv., August 1, 2005; 5(4): 226 - 240. [Abstract] [Full Text] [PDF]