标题:5′-triphosphate siRNA targeting HBx elicits a potent anti-HBV immune response in pAAV-HBV transfected mice
作者:Han Q.; Hou Z.; Yin C.; Zhang C.; Zhang J.
作者机构:[Han, Q] Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, 44 Wenhua West Road, Jinan, 250012, China 更多
通讯作者:Zhang, J(zhangj65@sdu.edu.cn)
通讯作者地址:[Zhang, J] Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, 44 Wenhua West Road, China;
来源:Antiviral Research
出版年:2019
卷:161
页码:36-45
DOI:10.1016/j.antiviral.2018.11.006
关键词:HBV; Immunotherapy; RIG-I; RNA interference
摘要:RNA with 5′-triphosphate (3p-RNA) is recognized by RNA sensor RIG-I (retinoic acid–inducible gene I protein). Previously, we reported that small interfering RNA targeting HBx (3p-siHBx) could confer potent anti–hepatitis B virus (HBV) efficacy via HBx silencing and RIG-I activation. However, the characteristics of innate and adaptive immunity especially exhaustion profiles in the liver microenvironment in response to 3p-siHBx therapy have not been fully elucidated. Here, we observed that 3p-siHBx more significantly inhibited HBV replication in vivo. 3p-siHBx enhanced natural killer (NK) cell activation with KLRG1 and CD69 upregulation and interferon (IFN)-γ secretion. 3p-siHBx significantly reversed the exhaustion phenotype of CD8 + T cells, and augmented CD8 + T cell activation and function. Importantly, 3p-siHBx disrupted the differentiation of myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg), accompanied by the reduction of the immunosuppressive cytokines interleukin (IL)-10 and transforming growth factor (TGF)-β. 3p-siHBx also enhanced dendritic cell maturation. Further investigation showed that RIG-I was involved in 3p-siHBx–induced IFN-α, IFN-β, and IFN-λ production. Moreover, RIG-I activation in HBV + hepatocytes would improve the recruitment of CD8 + T cells and NK cells. These results reveal that 3p-siHBx therapy can improve the immune microenvironment in HBV-carrier liver and inhibit HBV replication, indicating the potential utility of RIG-I ligands as molecular adjuvants for viral vaccines or candidate drugs. © 2018 Elsevier B.V.
收录类别:SCOPUS
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85056792478&doi=10.1016%2fj.antiviral.2018.11.006&partnerID=40&md5=ccb0e57c020ddcd0af3ea27e6af150c4
TOP