title: Hepatitis C virus alternate reading frame protein decreases interferon-α secretion in peripheral blood mononuclear cells.
abstract: The hepatitis C virus (HCV) alternate reading frame protein (ARFP or F protein) of the HCV 1b genotype is a double-frameshift product of the HCV core protein (Core). The discovery of HCV F protein challenges various biological functions attributed to Core. However, the specific characteristics of the host cellular immune response to F protein during HCV infection have yet to be fully elucidated. Therefore, the present study investigated the cytokine response to HCV Core or F protein in peripheral blood mononuclear cells (PBMCs) and plasmacytoid dendritic cells (PDCs) from patients with chronic HCV and healthy donors in vitro. The results demonstrated that the levels of interferon (IFN)-α, analyzed by an enzyme-linked immunosorbent assay, secreted by PBMCs in patients positive for the anti-F protein antibody, were lower than those of patients negative for the anti-F protein antibody. Moreover, the frequency of PDCs in patients negative for the anti-F protein antibody, were higher than in the group positive for the anti-F protein antibody. Furthermore, HCV F protein and Core not only inhibited specific unmethylated CpG oligonucleotide sequences of type A (CpG‑A)-induced IFN-α production by PBMCs and PDCs, but also upregulated the production of interleukin (IL)-10 by PBMCs in patients with chronic HCV and healthy controls. Notably, following neutralization of IL-10 in the media and in vitro Core or F protein stimulation, levels of IFN-α were increased. Moreover, the results revealed that the roles of F protein and Core were similar with regard to the induction of apoptosis of PDCs in patients with chronic HCV. These findings suggest that F protein may inhibit PBMC IFN-α secretion by regulating the production of IL-10, and may contribute to an increase in the rates of apoptosis in PDCs. In conclusion, the results have revealed a potential involvement of F protein in the mechanisms of chronic hepatitis C.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Xiaozhao
authors.initials: X
authors.lastname: Deng
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yue
authors.affiliation: Huadong Research Institute for Medicine and Biotechnics, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Jinhai
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Danyan
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Clinical Laboratory, Nanjing Second Hospital, Nanjing, Jiangsu 210003, P.R. China.
authors.forename: Zhenxian
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Acute Infectious Disease Control and Prevention, Jiangsu Province Center for Disease Prevention and Control, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Zhai
authors.affiliation: Department of Acute Infectious Disease Control and Prevention, Jiangsu Province Center for Disease Prevention and Control, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.affiliation: Huadong Research Institute for Medicine and Biotechnics, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D005260:Female; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D016174:Hepacivirus / Q000737:chemistry / Q000235:genetics*; D006526:Hepatitis C / Q000235:genetics / Q000378:metabolism / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016364:Reading Frames / Q000235:genetics; D014758:Viral Core Proteins / Q000235:genetics* / Q000276:immunology
chemical_list: D016898:Interferon-alpha; D014758:Viral Core Proteins; C433031:hepatitis C protein F, Hepatitis C virus