title: Impairment of the retinoic acid-inducible gene-I-IFN-β signaling pathway             in chronic hepatitis B virus infection.
abstract: Chronic hepatitis B (CHB) virus infection is caused by compromised host immunity, but the precise underlying mechanism remains unclear. Retinoic acid-inducible gene I (RIG-I) triggers antiviral immunity by inducing interferon-β (IFN-β) production following viral infection. To investigate the role of the RIG-I-IFN-β signaling pathway in monocyte-derived dendritic cells (moDCs) during CHB infection, moDCs were generated by stimulating CD14+ monocytes in vitro. MoDCs from patients with CHB, acute hepatitis B (AHB) and healthy controls (HCs) were challenged with vesicular stomatitis virus (VSV) and the levels of RIG-I, IFN-β promoter stimulator 1 (IPS-1) and IFN-β in the stimulated moDCs were determined. Following 16 h of VSV stimulation, RIG-I expression was reduced by 50% in moDCs from CHB patients and by 70% in moDCs from AHB patients relative to HC moDCs, concomitant with a 20% decrease in IFN-β expression in CHB patients relative to AHB patients and HCs. Additionally, a significant correlation between the RIG-I/IPS-1 ratio and alanine aminotransferase (ALT) level was observed. To further investigate the function of RIG-I in chronic hepatitis B virus (HBV) infection, HepG2 or HepG2.2.15 (HBV-transformed) cell lines were challenged with VSV following RIG-1 transfection. IFN-β induction was suppressed in HepG2.2.15 cells, but was restored following RIG-I transfection. Taken together, these data indicate that compromised moDC function in CHB patients is attributable to an impaired RIG-I-IFN-β signaling pathway, which results in compromised host viral clearance and HBV persistence in a susceptible population.
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, Shanghai                     Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Gangde
authors.initials: G
authors.lastname: Zhao
authors.forename: Baoyan
authors.initials: B
authors.lastname: An
authors.forename: Huijuan
authors.initials: H
authors.lastname: Zhou
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Yumin
authors.initials: Y
authors.lastname: Xu
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Xiang
authors.forename: Zhixia
authors.initials: Z
authors.lastname: Dong
authors.forename: Fangmei
authors.initials: F
authors.lastname: An
authors.forename: Dongshan
authors.initials: D
authors.lastname: Yu
authors.forename: Weijing
authors.initials: W
authors.lastname: Wang
authors.forename: Shisan
authors.initials: S
authors.lastname: Bao
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000328:Adult; D016022:Case-Control Studies; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism / Q000821:virology; D005260:Female; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism*; D008297:Male; D011971:Receptors, Immunologic; D015398:Signal Transduction; D015533:Transcriptional Activation; D018116:Vesiculovirus / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C505371:MAVS protein, human; D011971:Receptors, Immunologic; D016899:Interferon-beta; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases