Desmethoxycurcumin aids IFNα's anti-HBV activity by antagonising CRYAB reduction and stabilising IFNAR1 protein

作者全名："Wei, Jinlai; Deng, Xichuan; Dai, Wenying; Xie, Lingxin; Zhang, Guangyuan; Fan, Xinyue; Li, Xinyue; Jin, Zhixing; Xiao, Qin; Chen, Tingting"

作者地址："[Wei, Jinlai] Chongqing Med Univ, Dept Gastrointestinal Surg, Affiliated Hosp 1, Chongqing, Peoples R China; [Deng, Xichuan; Dai, Wenying; Xie, Lingxin; Zhang, Guangyuan; Fan, Xinyue; Li, Xinyue; Jin, Zhixing; Chen, Tingting] Chongqing Med Univ, Lab Tissue & Cell Biol, Lab Teaching & Management Ctr, Chongqing, Peoples R China; [Zhang, Guangyuan; Chen, Tingting] Chongqing Med Univ, Pathogen Biol & Immunol Lab, Lab Teaching & Management Ctr, Chongqing, Peoples R China; [Xiao, Qin] Third Mil Med Univ, Natl Engn Res Ctr Immunol Prod, Dept Microbiol & Biochem Pharm, Chongqing, Peoples R China; [Xiao, Qin] Third Mil Med Univ, Natl Engn Res Ctr immunol Prod, Dept Microbiol & Biochem Pharm, Chongqing 400038, Peoples R China; [Chen, Tingting] Chongqing Med Univ, Lab Tissue & Cell Biol, Lab Teaching & Management Ctr, Chongqing 400016, Peoples R China"

通信作者："Xiao, Q (通讯作者)，Third Mil Med Univ, Natl Engn Res Ctr immunol Prod, Dept Microbiol & Biochem Pharm, Chongqing 400038, Peoples R China.; Chen, TT (通讯作者)，Chongqing Med Univ, Lab Tissue & Cell Biol, Lab Teaching & Management Ctr, Chongqing 400016, Peoples R China."

来源：JOURNAL OF DRUG TARGETING

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001091001900001

JCR分区：Q1

影响因子：4.3

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：DMC; IFNAR1 degradation; antagonize; cRYAB; HBV immune escape

摘要："The eradication of chronic hepatitis B (CHB) caused by hepatitis B virus (HBV) infection is a crucial goal in clinical practice. Enhancing the anti-HBV activity of interferon type I (IFNI) is a key strategy for achieving a functional cure for CHB. In this study, we investigated the effect of combined treatment with IFN alpha and Desmethoxycurcumin (DMC) on HBV replication in HepG2 cells and explored the underlying mechanism. Our results indicated IFN alpha alone was ineffective in completely inhibiting HBV replication, which was attributed to the virus-induced down-regulation of IFNI receptor 1 (IFNAR1) protein. However, the addition of a low dose of DMC significantly synergized with IFN alpha, leading to notable enhancement of IFN alpha anti-HBV activity. This effect was achieved by stabilising the IFNAR1 protein. Further investigation revealed that low dose DMC effectively blocked the ubiquitination-mediated degradation of IFNAR1, which was accomplished by rescuing the protein levels of alphaB-crystallin (CRYAB) and orchestrating the interaction between CRYAB and the E3 ubiquitin ligase, beta-Trcp. Importantly, over-expression of CRYAB was found to favour the antiviral activity of IFN alpha against HBV replication. In conclusion, our study demonstrates that low-dose DMC enhanced the anti-HBV activity of IFN alpha by counteracting the reduction of CRYAB and stabilising the IFNAR1 protein."

基金机构：We gratefully thank American Journal Experts for editing this manuscript.

基金资助正文：We gratefully thank American Journal Experts for editing this manuscript.