title: Ubiquitin-hepatitis B core antigen-cytoplasmic transduction peptide enhances HBV-specific humoral and CTL immune responses in vivo.
abstract: Therapeutic strategies based on an enhanced hepatitis B virus (HBV)-specific cytotoxic T lymphocyte (CTL) activity may eradicate HBV. We previously verified that a fusion protein ubiquitin (Ub)-hepatitis B core antigen (HBcAg)-cytoplasmic transduction peptide (CTP) can enter the cytoplasm of dendritic cells and enhance T cell response to generate HBV-specific CTLs efficiently in vitro. Ub, a marker of protein degradation, may promote the generation of peptides appropriate for major histocompatibility complex class I presentation. In the present study, the specific immune responses of the fusion protein Ub-HBcAg-CTP in BALB/c mice were evaluated and the underlying mechanisms were investigated. Results showed that Ub-HBcAg-CTP increased the anti-HBcAg titer and produced the cytokines IFN-γ and IL-2. This fusion protein also induced higher percentages of IFN-γ(+)CD8(+) cells and specific CTL responses. Ub-HBcAg-CTP could also upregulate the expressions of Jak2, Tyk2, STAT1, and STAT4 in T lymphocytes. In conclusion, Ub-HBcAg-CTP enhanced cellular and humoral immune responses and induced robust HBV-specific CTL activities in BALB/c mice.
authors.affiliation: Department of Infectious Disease, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Infectious Disease, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhuo
authors.affiliation: Department of Infectious Disease, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Infectious Disease, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Infectious Disease, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: tzhhao@163.com.
authors.forename: Zhenghao
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of Infectious Disease, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: professorzangtg@126.com.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zang
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D006509:Hepatitis B / Q000276:immunology / Q000628:therapy*; D006510:Hepatitis B Antibodies / Q000097:blood; D006512:Hepatitis B Core Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050797:STAT4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D014452:Ubiquitins / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D050794:STAT1 Transcription Factor; D050797:STAT4 Transcription Factor; D014452:Ubiquitins; D054321:rev Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2
keywords: Cytoplasmic transduction peptide; Cytotoxic T lymphocyte; Hepatitis B core antigen; JAK/STAT signaling pathway; Ubiquitin