title: BST2/Tetherin inhibits hepatitis C virus production in human hepatoma cells.
abstract: Hepatitis C virus (HCV) infection is a common cause of chronic hepatitis and is currently treated with alpha interferon (IFN-α)-based therapies. IFN-induced cell membrane protein BST2 (also known as CD317, HM1.24 or tetherin) has been reported to tether a broad range of lipid-enveloped viruses on cell surfaces. However, whether HCV is sensitive to BST2 remains controversial. Here we established a Huh7.5-BST2-TO cell line, in which BST2 expression is regulated by tetracycline. Our results showed that the effect of BST2 on inhibiting HCV production was dependent on its expression level. Highly expressed BST2 reduced the yield of cell-free HCV virions but did not affect the efficiency of HCV infection and genome replication. Co-localization of HCV core protein and BST2 was detected by immunofluorescence in certain cells with high expression, but not in cells with low BST2 expression. Furthermore, inhibition of IFN-α induced BST2 expression in Huh7.5 cells by siRNA technology slightly reduced the antiviral response of the cytokine against HCV, but only at low IFN-α concentration. While overexpression of BST2 inhibited HCV replication in this system, BST2 is therefore not likely to be a major contributor to the antiviral effect of IFN-α.
authors: Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing 100044, PR China. panxiaoben@pkuph.edu.cn
authors: Xiao-Ben
authors: XB
authors: Pan
authors: Xiao-Wang
authors: XW
authors: Qu
authors: Dong
authors: D
authors: Jiang
authors: Xing-Liang
authors: XL
authors: Zhao
authors: Jin-Chao
authors: JC
authors: Han
authors: Lai
authors: L
authors: Wei
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D045744:Cell Line, Tumor; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D021381:Protein Transport; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D014764:Viral Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2