title: Hepatitis B virus e antigen physically associates with receptor-interacting serine/threonine protein kinase 2 and regulates IL-6 gene expression.
abstract: We previously reported that hepatitis B virus (HBV) e antigen (HBeAg) inhibits production of interleukin 6 by suppressing NF-κB activation. NF-κB is known to be activated through receptor-interacting serine/threonine protein kinase 2 (RIPK2), and we examined the mechanisms of interleukin 6 regulation by HBeAg. HBeAg inhibits RIPK2 expression and interacts with RIPK2, which may represent 2 mechanisms through which HBeAg blocks nucleotide-binding oligomerization domain-containing protein 1 ligand-induced NF-κB activation in HepG2 cells. Our findings identified novel molecular mechanisms whereby HBeAg modulates intracellular signaling pathways by targeting RIPK2, supporting the concept that HBeAg could impair both innate and adaptive immune responses to promote chronic HBV infection.
authors.affiliation: Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wu
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kanda
authors.forename: Fumio
authors.initials: F
authors.lastname: Imazeki
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Makoto
authors.initials: M
authors.lastname: Arai
authors.forename: Thierry
authors.initials: T
authors.lastname: Roger
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shirasawa
authors.forename: Fumio
authors.initials: F
authors.lastname: Nomura
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
mesh_terms: D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000502:physiology; D006513:Hepatitis B e Antigens / Q000737:chemistry / Q000378:metabolism*; D006515:Hepatitis B virus; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2 / Q000378:metabolism*
chemical_list: D006513:Hepatitis B e Antigens; C508600:IL6 protein, human; D015850:Interleukin-6; D016328:NF-kappa B; C506253:RIPK2 protein, human; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2