title: MicroRNA-26b inhibits hepatitis B virus transcription and replication by targeting the host factor CHORDC1 protein.
abstract: Hepatitis B virus (HBV) causes acute and chronic hepatitis in humans, and HBV infection is a major threat to global health. HBV replication is regulated by a series of host factors, including microRNAs (miRNAs), which are highly conserved small noncoding RNAs that participate in a variety of physiological and pathological processes. Here, we report that a chemically synthesized mimic of miR-26b inhibited HBV antigen expression, transcription, and replication, whereas antisense knockdown of endogenous miR-26b enhanced HBV replication in HepG2 cells. Overexpression and knockdown experiments showed that miR-26b significantly decreased HBV enhancer/promoter activities. We identified the cysteine- and histidine-rich domain containing 1 (CHORDC1) as a novel host factor target of miR-26b. CHORDC1 protein but not mRNA was markedly decreased by miR-26b overexpression via base-pairing with complementary sequences in the 3'UTR of its mRNA. Overexpression and knockdown studies showed that CHORDC1 increased viral antigen expression, transcription, and replication by elevating HBV enhancer/promoter activities. Conversely, HBV infection suppressed miR-26b expression and increased CHORDC1 protein levels in human liver cells. Another mature miRNA of the hsa-miR-26 family, miR-26a, had a similar function as miR-26b in targeting CHORDC1 and affecting HBV production. These results suggest that suppression of miR-26b expression up-regulates its target gene CHORDC1, which increases HBV enhancer/promoter activities and promotes viral transcription, gene expression, and replication. Our study could provide new insights into miRNA expression and the persistence of HBV infection.
authors.affiliation: From the State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, Hubei, China.
authors.forename: Fanpeng
authors.initials: F
authors.lastname: Zhao
authors.affiliation: From the State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, Hubei, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.affiliation: From the State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, Hubei, China.
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: From the State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, Hubei, China.
authors.forename: Lvyin
authors.initials: L
authors.lastname: Wang
authors.affiliation: From the State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, Hubei, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Xie
authors.affiliation: From the State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, Hubei, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Ren
authors.affiliation: From the State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, Hubei, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Liu
authors.affiliation: From the State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, Hubei, China yingzhu@whu.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000821:virology; D035683:MicroRNAs / Q000235:genetics*; D028044:Phosphate-Binding Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D035683:MicroRNAs; D028044:Phosphate-Binding Proteins; C548819:CHORDC1 protein, human; C528163:MIRN26 microRNA, human
keywords: CHORDC1; Hepatitis B Virus; Hepatitis Virus; Host Factor; Host-Pathogen Interaction; Infectious Disease; MicroRNA (miRNA); MicroRNA-26b; Viral Infection; Viral Transcription