Natural killer cells suppress full cycle HCV infection of human hepatocytes.
The role of natural killer (NK) cells in controlling hepatitis C virus (HCV) infection and replication has not been fully delineated. We examined NK cell-mediated noncytolytic effect on full cycle HCV infection of human hepatocytes. Human hepatocytes (Huh7.5.1 cells) co-cultured with NK cells or treated with supernatants (SN) from NK cells cultures had significantly lower levels of HCV RNA and protein than control cells. This NK cell-mediated anti-HCV activity could be largely abolished by antibody to interferon-gamma (IFN-gamma). The investigation of the mechanisms for NK cell-mediated anti-HCV activity showed that NK SN-treated hepatocytes expressed higher levels of IFN-alpha/beta than the control cells. NK SN also enhanced IFN regulatory factor-3 and 7 expression in the hepatocytes. In addition, NK SN enhanced the expression of signal transducer and activator of transcription 1 and 2, the nuclear factors that are essential for the activation of IFN-mediated antiviral pathways. These data provide direct evidence at cellular and molecular levels that NK cells have a key role in suppressing HCV infection of and replication in human hepatocytes.
Wang
S-H
SH
Division of Allergy and Immunology, Joseph Stokes Jr. Research Institute at The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Huang
C-X
CX
Ye
L
L
Wang
X
X
Song
L
L
Wang
Y-J
YJ
Liang
H
H
Huang
X-Y
XY
Ho
W-Z
WZ
D000328:Adult; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D016174:Hepacivirus / Q000276:immunology* / Q000502:physiology; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology; D022781:Hepatocytes / Q000276:immunology* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D015398:Signal Transduction; D014779:Virus Replication
D007372:Interferons