title: Hepatitis B virus antigens impair NK cell function.
abstract: An inadequate immune response of the host is thought to be a critical factor causing chronic hepatitis B virus (CHB) infection. Natural killer (NK) cells, as one of the key players in the eradication and control of viral infections, were functionally impaired in CHB patients, which might contribute to viral persistence. Here, we reported that HBV antigens HBsAg and HBeAg directly inhibited NK cell function. HBsAg and/or HBeAg blocked NK cell activation, cytokine production and cytotoxic granule release in human NK cell-line NK-92 cells, which might be related to the downregulation of activating receptors and upregulation of inhibitory receptor. Furthermore, the underlying mechanisms likely involved the suppression of STAT1, NF-κB and p38 MAPK pathways. These findings implicated that HBV antigen-mediated inhibition of NK cells might be an efficient strategy for HBV evasion, targeting the early antiviral responses mediated by NK cells and resulting in the establishment of chronic virus infection. Therefore, this study revealed the relationship between viral antigens and human immune function, especially a potential important interaction between HBV and innate immune responses.
authors.affiliation: State Key Lab of Microbial Technology, National Glycoengineering Research Center, Shandong University, China; Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, China.
authors.forename: Yinli
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, China.
authors.forename: Qiuju
authors.initials: Q
authors.lastname: Han
authors.affiliation: Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, China.
authors.forename: Cai
authors.initials: C
authors.lastname: Zhang
authors.affiliation: State Key Lab of Microbial Technology, National Glycoengineering Research Center, Shandong University, China; Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, China. Electronic address: minxiao@sdu.edu.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Xiao
authors.affiliation: Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, China. Electronic address: zhangj65@sdu.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D005260:Female; D006509:Hepatitis B / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000378:metabolism*; D006513:Hepatitis B e Antigens / Q000378:metabolism*; D019694:Hepatitis B, Chronic / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D056747:Immunomodulation; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D017735:Virus Latency; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D016328:NF-kappa B; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D048051:p38 Mitogen-Activated Protein Kinases
keywords: HBeAg; HBsAg; NF-κB; Natural killer cell; STAT1; p38 MAPK