title: Borna disease virus encoded phosphoprotein inhibits host innate immunity by regulating miR-155.
abstract: It has been reported that the Borna disease virus (BDV) encoded phosphoprotein (P protein) can inhibit the activity of Traf family member-associated NF-kappaB activator (TANK)-binding kinase 1 (TBK-1), thus preventing the induction of type I interferon (IFN). However, the effects of microRNA on the regulation of BDV infection and the host's immune response have not been characterized. miR-155 was predicted to be complementary to the BDV P mRNA by RNAhybrid software. Here, we showed that miR-155 was down-regulated in BDV persistently infected human oligodendroglial (OL/BDV) cells and that the BDV P protein, but not the X protein, directly inhibited miR-155 expression in cells. When miR-155 was over-expressed, the inhibition of type I IFNs by BDV in cells was reversed, and the expression of type I IFNs was increased. When miR-155 expression was specifically blocked, cellular IFN expression and the induction of IFN by poly I:C treatment were suppressed. Furthermore, miR-155 promoted type I IFN production by targeting suppressor of cytokine signaling 1 (SOCS1) and SOCS3. Mutations in the nt1138-nt1158 region of SOCS3 abandoned the impact of miR-155 on the expression of SOCS3-enhanced green fluorescent protein (EGFP). The levels of BDV P mRNA and protein were significantly decreased in OL/BDV cells when miR-155 was over-expressed; however, miR-155-mutation did not affect the expression of BDV P-EGFP. Thus, BDV persistent infection inhibited the expression of type I IFNs through the suppression of miR-155, and miR-155 played an important immune regulatory role in BDV persistent infection.
authors: The Heilongjiang Key Laboratory of Immunity and Infection, Key Laboratory of Pathogenic Biology Heilongjiang Higher Education Institutions, Department of Microbiology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors: Aixia
authors: A
authors: Zhai
authors: Jun
authors: J
authors: Qian
authors: Wenping
authors: W
authors: Kao
authors: Aimei
authors: A
authors: Li
authors: Yujun
authors: Y
authors: Li
authors: Junming
authors: J
authors: He
authors: Qingmeng
authors: Q
authors: Zhang
authors: Wuqi
authors: W
authors: Song
authors: Yingmei
authors: Y
authors: Fu
authors: Jing
authors: J
authors: Wu
authors: Xiaobei
authors: X
authors: Chen
authors: Hui
authors: H
authors: Li
authors: Zhaohua
authors: Z
authors: Zhong
authors: Hong
authors: H
authors: Ling
authors: Fengmin
authors: F
authors: Zhang
mesh_terms: D001890:Borna Disease / Q000235:genetics / Q000276:immunology* / Q000821:virology; D001891:Borna disease virus / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology; D035683:MicroRNAs / Q000235:genetics* / Q000276:immunology; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology*; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D007370:Interferon Type I; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C496537:P protein, Borna disease virus; D010750:Phosphoproteins; D015678:Viral Structural Proteins