Hepatitis C virus NS4 protein impairs the Th1 polarization of immature dendritic cells.

Abstract:

:Dendritic cells (DCs) in chronic hepatitis C patients display impaired function, although the details remain unclear. To investigate the hepatitis C virus (HCV) protein that has the most impact on DC function, we compared five recombinant proteins and seven HCV protein genes in modulating DC phenotype and function. Immature DCs (iDCs) were established from healthy donor peripheral blood monocytes with granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-4. Lipopolysaccharide was used to establish mature DCs (mDCs). Cells were then pulsed with HCV recombinant proteins or transfected with HCV plasmids and subsequently assayed for cell surface marker expression by flow cytometry. For cytokine and proliferative T-cell response analysis, DCs were cultured with autologous CD4 T cells and tuberculin purified protein derivative (PPD). Mean fluorescent intensity of CD86 was reduced in HCV protein-pulsed iDCs. Proliferative T-cell responses and Th1 cytokine concentrations were reduced with HCV nonstructural proteins (NS), particularly with HCV NS4. HCV nonstructural proteins, particularly NS4, change the iDC phenotype and reduce antigen-specific T-cell stimulatory function with Th1 cytokine reductions.

journal_name

J Viral Hepat

authors

Takaki A,Tatsukawa M,Iwasaki Y,Koike K,Noguchi Y,Shiraha H,Sakaguchi K,Nakayama E,Yamamoto K

doi

10.1111/j.1365-2893.2009.01213.x

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

555-62

issue

8

eissn

1352-0504

issn

1365-2893

pii

JVH1213

journal_volume

17

pub_type

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