title: Hepatitis B virus spliced variants are associated with an impaired response to interferon therapy.
abstract: During hepatitis B virus (HBV) replication, spliced HBV genomes and splice-generated proteins have been widely described, however, their biological and clinical significance remains to be defined. Here, an elevation of the proportion of HBV spliced variants in the sera of patients with chronic hepatitis B (CHB) is shown to correlate with an impaired respond to interferon-α (IFN-α) therapy. Transfection of the constructs encoding the three most dominant species of spliced variants into cells or ectopic expression of the two major spliced protein including HBSP and N-terminal-truncated viral polymerase protein result in strong suppression of IFN-α signaling transduction, while mutation of the major splicing-related sites of HBV attenuates the viral anti-IFN activities in both cell and mouse models. These results have associated the productions of HBV spliced variants with the failure response to IFN therapy and illuminate a novel mechanism where spliced viral products are employed to resist IFN-mediated host defense.
authors.affiliation: Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, China.
authors.forename: Jieliang
authors.initials: J
authors.lastname: Chen
authors.affiliation: Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.affiliation: Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.affiliation: Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Huashan Hospital affiliated to Fudan University, China.
authors.forename: Jiming
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, China.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, China.
authors.forename: Yunwen
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, China.|Institutes of Medical Microbiology and Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D001483:Base Sequence; D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D012689:Sequence Homology, Nucleic Acid; D014764:Viral Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D016898:Interferon-alpha; D014764:Viral Proteins