title: 2',3'-cyclic nucleotide 3'-phosphodiesterases inhibit hepatitis B virus replication.
abstract: 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) is a member of the interferon-stimulated genes, which includes isoforms CNP1 and CNP2. CNP1 is locally expressed in the myelin sheath but CNP2 is additionally expressed at low levels outside the nervous system. CNPs regulate multiple cellular functions and suppress protein production by association with polyadenylation of mRNA. Polyadenylation of Hepatitis B virus (HBV) RNAs is crucial for HBV replication. Whether CNPs interact with polyadenylation signal of HBV RNAs and interfere HBV replication is unknown. In this study, we evaluated expressions of CNP isoforms in hepatoma cell lines and their effects on HBV replication. We found that CNP2 is moderately expressed and gently responded to interferon treatment in HepG2, but not in Huh7 cells. The CNP1 and CNP2 potently inhibited HBV production by blocking viral proteins synthesis and reducing viral RNAs, respectively. In chronic hepatitis B patients, CNP was expressed in most of HBV-infected hepatocytes of liver specimens. Knockdown of CNP expression moderately improved viral production in the HepG2.2.15 cells treated with IFN-α. In conclusion, CNP might be a mediator of interferon-induced response against HBV.
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, P. R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ma
authors.forename: Xing-Liang
authors.initials: XL
authors.lastname: Zhao
authors.forename: Xue-Yan
authors.initials: XY
authors.lastname: Wang
authors.forename: Xing-Wang
authors.initials: XW
authors.lastname: Xie
authors.forename: Jin-Chao
authors.initials: JC
authors.lastname: Han
authors.forename: Wen-Li
authors.initials: WL
authors.lastname: Guan
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.forename: Xiao-Ben
authors.initials: XB
authors.lastname: Pan
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
mesh_terms: D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006515:Hepatitis B virus / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000235:genetics / Q000378:metabolism / Q000821:virology; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D007527:Isoenzymes; D008099:Liver / Q000378:metabolism / Q000821:virology; D021381:Protein Transport; D014779:Virus Replication
chemical_list: D007527:Isoenzymes; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase