title: Potential Role of Hepatitis C Virus Alternate Reading Frame Protein in Negative Regulation of T-Bet Gene Expression.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Dan Yan
authors.initials: DY
authors.lastname: Zhu
authors.forename: Xiao Zhao
authors.initials: XZ
authors.lastname: Deng
authors.forename: Long Feng
authors.initials: LF
authors.lastname: Jiang
authors.forename: Wen
authors.initials: W
authors.lastname: Xiao
authors.forename: Jia Ping
authors.initials: JP
authors.lastname: Pei
authors.forename: Bing Jun
authors.initials: BJ
authors.lastname: Li
authors.forename: Chang Jun
authors.initials: CJ
authors.lastname: Wang
authors.forename: Jin Hai
authors.initials: JH
authors.lastname: Zhang
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Zhen Xian
authors.initials: ZX
authors.lastname: Zhou
authors.forename: Wei Liang
authors.initials: WL
authors.lastname: Ding
authors.forename: Xiao Dong
authors.initials: XD
authors.lastname: Xu
authors.forename: Ming
authors.initials: M
authors.lastname: Yue
mesh_terms: D000328:Adult; D005260:Female; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000502:physiology / Q000821:virology; D008297:Male; D008875:Middle Aged; D016364:Reading Frames / Q000502:physiology*; D020825:T-Box Domain Proteins / Q000096:biosynthesis* / Q000235:genetics; D014758:Viral Core Proteins / Q000502:physiology*; D000098815:T-bet Transcription Factor
chemical_list: D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014758:Viral Core Proteins; C433031:hepatitis C protein F, Hepatitis C virus