title: A cross-talk between Hepatitis B virus and host mRNAs confers viral adaptation to liver.
abstract: Hepatitis B virus (HBV) chronically infects approximately 350 million people worldwide. The replication of HBV which genome is only 3.2 kb long relies heavily on host factors. Previous studies demonstrated that a highly expressed liver-specific microRNA (miRNA) miR-122 suppresses HBV expression and replication in multiple ways. In this study, we found that the miR-122 response elements in viral genome facilitate HBV expression and replication in miR-122 highly-expressed hepatocytes. Moreover, mutations in miR-122 response elements are correlated with viral loads and disease progression in HBV-infected patients. We next found that HBV mRNA with miR-122 response elements alone could lead to altered expression of multiple host genes by whole genome expression analysis. HBV mRNA-mediated miR-122 down-regulation plays a major role in HBV mRNA-induced differential gene expression. HBV mRNA could enhance viral replication via miR-122 degradation and the up-regulation of its target cyclin G1. Our study thereby reveals that under the unique condition of high abundance of miR-122 and viral mRNAs and much lower level of miR-122 target in HBV infection, HBV may have evolved to employ the miRNA-mediated virus and host mRNAs network for optimal fitness within hepatocytes.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
authors.forename: Yaxing
authors.initials: Y
authors.lastname: Xu
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
authors.forename: Changfei
authors.initials: C
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
authors.forename: Junli
authors.initials: J
authors.lastname: Hao
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
authors.forename: Shanxin
authors.initials: S
authors.lastname: Peng
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Chu
authors.affiliation: Laboratory of Disease Genomics and Individualized Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Dake
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Institute of Infectious Diseases/Liver Failure Medical Center, Beijing 302 Hospital, Beijing, China.
authors.forename: Dongping
authors.initials: D
authors.lastname: Xu
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
authors.forename: Songdong
authors.initials: S
authors.lastname: Meng
mesh_terms: D020413:3' Untranslated Regions; D000220:Adaptation, Biological; D000328:Adult; D001483:Base Sequence; D001665:Binding Sites; D018450:Disease Progression; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006509:Hepatitis B / Q000235:genetics* / Q000821:virology*; D006515:Hepatitis B virus / Q000502:physiology*; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000821:virology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics*; D020218:Response Elements; D019562:Viral Load; D014779:Virus Replication
chemical_list: D020413:3' Untranslated Regions; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D012367:RNA, Viral