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Potential Role of Hepatitis C Virus Alternate Reading Frame Protein in Negative Regulation of T-Bet Gene Expression

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Journal Inflammation
Date 2015 Apr 21
PMID 25894282
Citations 4
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Abstract

Hepatitis C virus (HCV) is a major cause of chronic liver disease and has led to cirrhosis or hepatocellular carcinoma in a majority of infected individuals. We have previously demonstrated that the HCV alternate reading frame protein (F protein) is related to Th1/Th2 bias in chronic hepatitis C (CHC) patients, and we aimed to explore the relative molecular mechanisms here. A total of 104 cases including CHC patients and healthy donors were enrolled. T-bet and GATA-3 expression levels were analyzed in peripheral blood mononuclear cells (PBMCs). The levels of signal transducer and activator of transcription-1/-6(STAT1/6) and phosphorylated STAT1/6(pSTAT1/6) in PBMCs were measured by Western blotting. Our results showed that the levels of T-bet in PBMCs, as well as the levels of gamma interferon (IFN-γ) in sera, were decreased in anti-F protein antibody seropositive patients compared with anti-F protein antibody seronegative patients, whereas the levels of GATA-3 did not show difference between the two groups. Moreover, the decreased pSTAT1 and increased pSTAT6 were observed in PBMCs by HCV core/F protein stimulation with constant STAT1/6 expression. Taken together, it suggested that T-bet may be involved in Th1/Th2 bias induced by HCV F protein, and the disruption of STAT phosphorylation may participate in this mediation.

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References
1.
Lechner F, Wong D, Dunbar P, Chapman R, Chung R, Dohrenwend P . Analysis of successful immune responses in persons infected with hepatitis C virus. J Exp Med. 2000; 191(9):1499-512. PMC: 2213430. DOI: 10.1084/jem.191.9.1499. View

2.
Forbes E, van Panhuys N, Min B, Le Gros G . Differential requirements for IL-4/STAT6 signalling in CD4 T-cell fate determination and Th2-immune effector responses. Immunol Cell Biol. 2009; 88(3):240-3. DOI: 10.1038/icb.2009.101. View

3.
Farrar J, Ouyang W, Lohning M, Assenmacher M, Radbruch A, Kanagawa O . An instructive component in T helper cell type 2 (Th2) development mediated by GATA-3. J Exp Med. 2001; 193(5):643-50. PMC: 2193395. DOI: 10.1084/jem.193.5.643. View

4.
Kitamura N, Kitamura F, Kaminuma O, Miyatake S, Tatsumi H, Nemoto S . IL-4 gene transcription in human T cells is suppressed by T-bet. Int Arch Allergy Immunol. 2007; 143 Suppl 1:68-70. DOI: 10.1159/000101408. View

5.
Varaklioti A, Vassilaki N, Georgopoulou U, Mavromara P . Alternate translation occurs within the core coding region of the hepatitis C viral genome. J Biol Chem. 2002; 277(20):17713-21. DOI: 10.1074/jbc.M201722200. View