Identification of hepatitis C virus core domain inducing suppression of allostimulatory capacity of dendritic cells.
Hepatitis C virus (HCV) is remarkably efficient at establishing chronic infection. One of the reasons for this appears to be the suppression of the accessory cell function of professional antigen presenting cells. In the present study, the immunosuppressive activity of HCV protein was examined on dendritic cells (DCs) generated from mouse bone marrow progenitor cells in vitro. We found that the DCs forced to express HCV protein have defective allostimulatory ability. DCs expressing HCV protein were phenotypically indistinguishable from normal DCs. However, they were unable to produce IL-12 effectively when stimulated with lipopolysaccharide. The functional domain of the HCV protein essential for immunosuppression was determined using a series of NH2-and C-terminal deletion mutants of HCV core protein. We found that amino acid residues residing between the 21st and the 40th residues from the NH2-terminus of HCV core protein are required for immunosuppression. These findings suggest that HCV core protein suppresses the elicitation of protective Th1 responses by the inhibition of IL-12 production by DCs.
Kim
Ho Sang
HS
Department of Pharmacy, and Research Center for Bioresource and Health, Chungbuk National University, Cheongju, Korea.
Lee
Jae Kwon
JK
Yang
In Ho
IH
Ahn
Jeong Keun
JK
Oh
Yoon-I
YI
Kim
Chul Joong
CJ
Kim
Young Sang
YS
Lee
Chong-Kil
CK
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D016174:Hepacivirus / Q000737:chemistry* / Q000235:genetics; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000494:pharmacology*; D018664:Interleukin-12 / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics / Q000502:physiology; D010641:Phenotype; D010957:Plasmids / Q000235:genetics; D014162:Transfection; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D014758:Viral Core Proteins; D018664:Interleukin-12