PMID- 30019620 OWN - NLM STAT- MEDLINE DCOM- 20191101 LR - 20200930 IS - 1551-4005 (Electronic) IS - 1538-4101 (Print) IS - 1551-4005 (Linking) VI - 17 IP - 10 DP - 2018 TI - An engineered novel lentivector specifically transducing dendritic cells and eliciting robust HBV-specific CTL response by upregulating autophagy in T cells. PG - 1220-1234 LID - 10.1080/15384101.2018.1471312 [doi] AB - Dendritic cells (DCs) play a predominant role in initiating cell immune responses. Here we generated a DC-targeting lentiviral vector (LVDC-UbHBcAg-LIGHT) and evaluated its capacity to elicit HBV-specific cytotoxic T lymphocyte (CTL) responses. DC-SIGN-mediated specific transduction using this construct was confirmed in DC-SIGN-expressing 293T cells and ex vivo-cultured bone marrow cells. LVDC-UbHBcAg-LIGHT-loaded DCs were highly effective in inducing HBV-specific CTLs. Mechanistic studies demonstrated autophagy blocking led to a significant increase in apoptosis and obvious inhibition of CD8 + T cells entry into S-phase, correspondingly attenuated LVDC-UbHBcAg-LIGHT-loaded DC-induced T cell responses. This observation was supported by accumulation of pro-apoptotic proteins and the main negative cell cycle regulator-CDKN1B that otherwise would be degraded in activated T cells where autophagy preferentially occured. Our findings revealed an important role of autophagy in the activation of T cells and suggested LVDC-UbHBcAg-LIGHT may potentially be used as a therapeutic strategy to combat persistent HBV infection with higher security. FAU - Ma, Siyuan AU - Ma S AD - a Department of Infectious Disease , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China. FAU - Chen, Xiaohua AU - Chen X AD - a Department of Infectious Disease , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China. FAU - Tan, Quanhui AU - Tan Q AD - a Department of Infectious Disease , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China. FAU - Li, Dan AU - Li D AD - a Department of Infectious Disease , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China. FAU - Dai, Shenglan AU - Dai S AD - a Department of Infectious Disease , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China. FAU - Wu, Shanshan AU - Wu S AD - a Department of Infectious Disease , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China. FAU - Yu, Yongsheng AU - Yu Y AD - a Department of Infectious Disease , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China. FAU - Zang, Guoqing AU - Zang G AD - a Department of Infectious Disease , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China. FAU - Tang, Zhenghao AU - Tang Z AD - a Department of Infectious Disease , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180718 PL - United States TA - Cell Cycle JT - Cell cycle (Georgetown, Tex.) JID - 101137841 RN - 0 (Autophagy-Related Protein 5) RN - 0 (Cell Adhesion Molecules) RN - 0 (DC-specific ICAM-3 grabbing nonintegrin) RN - 0 (Hepatitis B Core Antigens) RN - 0 (Lectins, C-Type) RN - 0 (Receptors, Cell Surface) RN - 0 (Tumor Necrosis Factor Ligand Superfamily Member 14) RN - 0 (Ubiquitin) RN - 5142-23-4 (3-methyladenine) RN - JAC85A2161 (Adenine) SB - IM MH - Adenine/analogs & derivatives/pharmacology MH - Animals MH - Apoptosis/drug effects MH - *Autophagy/drug effects MH - Autophagy-Related Protein 5/metabolism MH - CD8-Positive T-Lymphocytes/immunology MH - Cell Adhesion Molecules/metabolism MH - Dendritic Cells/drug effects/*metabolism MH - Genetic Engineering MH - Genetic Vectors/*metabolism MH - Hepatitis B Core Antigens/metabolism MH - Hepatitis B virus/*immunology MH - Humans MH - Lectins, C-Type/metabolism MH - Lentivirus/*genetics MH - Lymphocyte Activation/drug effects/immunology MH - Mice, Inbred BALB C MH - Receptors, Cell Surface/metabolism MH - S Phase/drug effects MH - T-Lymphocytes, Cytotoxic/cytology/drug effects/*immunology/ultrastructure MH - *Transduction, Genetic MH - Tumor Necrosis Factor Ligand Superfamily Member 14/metabolism MH - Ubiquitin/metabolism MH - *Up-Regulation/drug effects PMC - PMC6110602 OTO - NOTNLM OT - Dendritic cell (DC)-targeting lentivector OT - autophagy OT - cytotoxic T lymphocyte (CTL) EDAT- 2018/07/19 06:00 MHDA- 2019/11/02 06:00 PMCR- 2019/07/18 CRDT- 2018/07/19 06:00 PHST- 2018/07/19 06:00 [pubmed] PHST- 2019/11/02 06:00 [medline] PHST- 2018/07/19 06:00 [entrez] PHST- 2019/07/18 00:00 [pmc-release] AID - 1471312 [pii] AID - 10.1080/15384101.2018.1471312 [doi] PST - ppublish SO - Cell Cycle. 2018;17(10):1220-1234. doi: 10.1080/15384101.2018.1471312. Epub 2018 Jul 18.