title: A liver-specific microRNA binds to a highly conserved RNA sequence of hepatitis B virus and negatively regulates viral gene expression and replication.
abstract: Regulated gene expression and progeny production are essential for persistent and chronic infection by human pathogens, such as hepatitis B virus (HBV), which affects >400 million people worldwide and is a major cause of liver disease. In this study, we provide the first direct evidence that a liver-specific microRNA, miR-122, binds to a highly conserved HBV pregenomic RNA sequence via base-pairing interactions and inhibits HBV gene expression and replication. The miR-122 target sequence is located at the coding region of the mRNA for the viral polymerase and the 3' untranslated region of the mRNA for the core protein. In cultured cells, HBV gene expression and replication reduces with increased expression of miR-122, and the expression of miR-122 decreases in the presence of HBV infection and replication. Furthermore, analyses of clinical samples demonstrated an inverse linear correlation in vivo between the miR-122 level and the viral loads in the peripheral blood mononuclear cells of HBV-positive patients. Our results suggest that miR-122 may down-regulate HBV replication by binding to the viral target sequence, contributing to the persistent/chronic infection of HBV, and that HBV-induced modulation of miR-122 expression may represent a mechanism to facilitate viral pathogenesis.
authors: State Key Laboratory of Virology and College of Life Sciences, Wuhan Institutes of Biotechnology, Chinese-French Liver Disease Research Institute at Zhongnan Hospital, Wuhan University, Wuhan, China.
authors: Yanni
authors: Y
authors: Chen
authors: Ao
authors: A
authors: Shen
authors: Paul J
authors: PJ
authors: Rider
authors: Yi
authors: Y
authors: Yu
authors: Kailang
authors: K
authors: Wu
authors: Yongxin
authors: Y
authors: Mu
authors: Qian
authors: Q
authors: Hao
authors: Yingle
authors: Y
authors: Liu
authors: Hao
authors: H
authors: Gong
authors: Ying
authors: Y
authors: Zhu
authors: Fenyong
authors: F
authors: Liu
authors: Jianguo
authors: J
authors: Wu
mesh_terms: D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D017124:Conserved Sequence; D017931:DNA Primers / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D015967:Gene Expression Regulation, Viral; D015684:Gene Products, pol / Q000235:genetics; D056945:Hep G2 Cells; D006509:Hepatitis B / Q000235:genetics / Q000378:metabolism / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000502:physiology; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000821:virology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism*; D014779:Virus Replication / Q000235:genetics / Q000502:physiology
chemical_list: D017931:DNA Primers; D015684:Gene Products, pol; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; C066027:P protein, Hepatitis B virus; D012333:RNA, Messenger; D012367:RNA, Viral