Impairment of the retinoic acid-inducible gene-I-IFN-β signaling pathway in chronic hepatitis B virus infection

  • Authors:
    • Gangde Zhao
    • Baoyan An
    • Huijuan Zhou
    • Hui Wang
    • Yumin Xu
    • Xiaogang Xiang
    • Zhixia Dong
    • Fangmei An
    • Dongshan Yu
    • Weijing Wang
    • Shisan Bao
    • Qing Xie
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  • Published online on: September 19, 2012     https://doi.org/10.3892/ijmm.2012.1131
  • Pages: 1498-1504
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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.
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December 2012
Volume 30 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Zhao G, An B, Zhou H, Wang H, Xu Y, Xiang X, Dong Z, An F, Yu D, Wang W, Wang W, et al: Impairment of the retinoic acid-inducible gene-I-IFN-β signaling pathway in chronic hepatitis B virus infection. Int J Mol Med 30: 1498-1504, 2012.
APA
Zhao, G., An, B., Zhou, H., Wang, H., Xu, Y., Xiang, X. ... Xie, Q. (2012). Impairment of the retinoic acid-inducible gene-I-IFN-β signaling pathway in chronic hepatitis B virus infection. International Journal of Molecular Medicine, 30, 1498-1504. https://doi.org/10.3892/ijmm.2012.1131
MLA
Zhao, G., An, B., Zhou, H., Wang, H., Xu, Y., Xiang, X., Dong, Z., An, F., Yu, D., Wang, W., Bao, S., Xie, Q."Impairment of the retinoic acid-inducible gene-I-IFN-β signaling pathway in chronic hepatitis B virus infection". International Journal of Molecular Medicine 30.6 (2012): 1498-1504.
Chicago
Zhao, G., An, B., Zhou, H., Wang, H., Xu, Y., Xiang, X., Dong, Z., An, F., Yu, D., Wang, W., Bao, S., Xie, Q."Impairment of the retinoic acid-inducible gene-I-IFN-β signaling pathway in chronic hepatitis B virus infection". International Journal of Molecular Medicine 30, no. 6 (2012): 1498-1504. https://doi.org/10.3892/ijmm.2012.1131