目前针对慢性乙型肝炎病毒(hepatitis B virus,HBV)感染的主要治疗手段是抗病毒治疗,但很难达到完全治愈,效果都不尽如人意。前基因组RNA(pregenomic RNA,pgRNA)是慢性HBV感染的新兴血清学标志物,是病毒蛋白和病毒DNA合成的模板,也是HBV...目前针对慢性乙型肝炎病毒(hepatitis B virus,HBV)感染的主要治疗手段是抗病毒治疗,但很难达到完全治愈,效果都不尽如人意。前基因组RNA(pregenomic RNA,pgRNA)是慢性HBV感染的新兴血清学标志物,是病毒蛋白和病毒DNA合成的模板,也是HBV cccDNA的直接转录产物。但最近已有研究发现了血清pgRNA的其他新功能。展开更多
Objective:To study the predictive value of serum pregenomic RNA(pgRNA)on HBeAg clearance in patients with chronic hepatitis B with low HBeAg levels during pegylated interferon therapy.Methods:Twenty chronic hepatitis ...Objective:To study the predictive value of serum pregenomic RNA(pgRNA)on HBeAg clearance in patients with chronic hepatitis B with low HBeAg levels during pegylated interferon therapy.Methods:Twenty chronic hepatitis B patients with HBeAg positive and quantitative<50S/CO were selected for this study.The subjects underwent pegylated interferon therapy for 48-96 weeks and were followed up in the outpatient clinic after treatment.The patients were then divided into groups based on whether their HbeAg turned negative.The predictive ability of each indicator for HBeAg negative conversion was evaluated in the HBeAg negative group and the HBeAg positive group.Results:The results of logistic regression analysis suggested that pgRNA and HBcrAg were better indicators for predicting the clearance of HBeAg after treatment.Conclusion:For patients with chronic hepatitis B with low HBeAg levels,pgRNA is a good indicator in predicting HBeAg clearance during pegylated interferon therapy.展开更多
Background:The hepatitis B virus(HBV)vaccine has been efficiently used for decades.However,hepatocellular carcinoma caused by HBV is still prevalent globally.We previously reported that interferon(IFN)-induced tripart...Background:The hepatitis B virus(HBV)vaccine has been efficiently used for decades.However,hepatocellular carcinoma caused by HBV is still prevalent globally.We previously reported that interferon(IFN)-induced tripartite motif-containing 25(TRIM25)inhibited HBV replication by increasing the IFN expression,and this study aimed to further clarify the anti-HBV mechanism of TRIM25.Methods:The TRIM25-mediated degradation of hepatitis B virus X(HBx)protein was determined by detecting the expression of HBx in TRIM25-overexpressed or knocked-out HepG2 or HepG2-NTCP cells via Western blotting.Co-immunoprecipitation was performed to confirm the interaction between TRIM25 and HBx,and colocalization of TRIM25 and HBx was identified via immunofluorescence;HBV e-antigen and HBV surface antigen were qualified by using an enzyme-linked immunosorbent assay(ELISA)kit from Kehua Biotech.TRIM25 mRNA,pregenomic RNA(pgRNA),and HBV DNA were detected by quantitative real-time polymerase chain reaction.The retinoic acid-inducible gene I(RIG-I)and pgRNA interaction was verified by RNA-binding protein immunoprecipitation assay.Results:We found that TRIM25 promoted HBx degradation,and confirmed that TRIM25 could enhance the K90-site ubiquitination of HBx as well as promote HBx degradation by the proteasome pathway.Interestingly,apart from the Really Interesting New Gene(RING)domain,the SPRY domain of TRIM25 was also indispensable for HBx degradation.In addition,we found that the expression of TRIM25 increased the recognition of HBV pgRNA by interacting with RIG-I,which further increased the IFN production,and SPRY,but not the RING domain is critical in this process.Conclusions:The study found that TRIM25 interacted with HBx and promoted HBx-K90-site ubiquitination,which led to HBx degradation.On the other hand,TRIM25 may function as an adaptor,which enhanced the recognition of pgRNA by RIG-I,thereby further promoting IFN production.Our study can contribute to a better understanding of host-virus interaction.展开更多
目的探讨金丝桃素对乙肝病毒(hepatitis B virus,HBV)启动子活性的影响。方法分别将构建好的带有病毒启动子的双荧光素酶报告基因系统及含有1.3倍HBV基因组的质粒转染到293T、L02及Hep G2细胞中,并对细胞进行分组给药。以去离子水为空...目的探讨金丝桃素对乙肝病毒(hepatitis B virus,HBV)启动子活性的影响。方法分别将构建好的带有病毒启动子的双荧光素酶报告基因系统及含有1.3倍HBV基因组的质粒转染到293T、L02及Hep G2细胞中,并对细胞进行分组给药。以去离子水为空白对照组,1.0μmol/L的拉米夫定为阴性对照组,浓度梯度的金丝桃素作为实验组;给药48 h后,收集细胞进行双荧光素酶指标检测及pgRNA表达水平的荧光定量PCR检测。结果在病毒启动子活性检测的结果中,金丝桃素组与拉米夫定组和空白对照组的结果一致,启动子活性变化不明显(P>0.05)。在pgRNA表达水平检测结果中,金丝桃素组与拉米夫定组和空白对照组在非肝源细胞株293T细胞中表达水平无显著变化(P>0.05),但在肝源细胞株L02、Hep G2中,金丝桃素组pgRNA的表达水平较其他两组明显下降(P<0.05)。结论金丝桃素可能不是通过影响病毒启动子,而是通过其他相关途径来发挥抗病毒的作用。展开更多
文摘目前针对慢性乙型肝炎病毒(hepatitis B virus,HBV)感染的主要治疗手段是抗病毒治疗,但很难达到完全治愈,效果都不尽如人意。前基因组RNA(pregenomic RNA,pgRNA)是慢性HBV感染的新兴血清学标志物,是病毒蛋白和病毒DNA合成的模板,也是HBV cccDNA的直接转录产物。但最近已有研究发现了血清pgRNA的其他新功能。
基金the grant from SPPH Incubator Fund for Development of Science and Technology(2021YJY-19)SPPH Foundation for Development of Science and Technology(2021BJ-26)International Science and Technology Cooperation Projects of Shaanxi Province(2022KW-14).
文摘Objective:To study the predictive value of serum pregenomic RNA(pgRNA)on HBeAg clearance in patients with chronic hepatitis B with low HBeAg levels during pegylated interferon therapy.Methods:Twenty chronic hepatitis B patients with HBeAg positive and quantitative<50S/CO were selected for this study.The subjects underwent pegylated interferon therapy for 48-96 weeks and were followed up in the outpatient clinic after treatment.The patients were then divided into groups based on whether their HbeAg turned negative.The predictive ability of each indicator for HBeAg negative conversion was evaluated in the HBeAg negative group and the HBeAg positive group.Results:The results of logistic regression analysis suggested that pgRNA and HBcrAg were better indicators for predicting the clearance of HBeAg after treatment.Conclusion:For patients with chronic hepatitis B with low HBeAg levels,pgRNA is a good indicator in predicting HBeAg clearance during pegylated interferon therapy.
基金National Natural Science Foundation,China(Nos.81801563,81901592,and 81801565)the 68th batch of first-class funding from the China Postdoctoral Science Foundation(No.2020M680044)+2 种基金the Natural Science Foundation of Jilin Province,Provincial Joint Fund Bethune Medical Project(Nos.20200201340JC,and 20210101338JC)the International Cooperation Project of Jilin Provincial Science and Technology Department(No.20220402085GH)Jilin University Excellent Young Teacher Training Program,and Bethune Project of Jilin University(Nos.2022B12,and 2018B24)
文摘Background:The hepatitis B virus(HBV)vaccine has been efficiently used for decades.However,hepatocellular carcinoma caused by HBV is still prevalent globally.We previously reported that interferon(IFN)-induced tripartite motif-containing 25(TRIM25)inhibited HBV replication by increasing the IFN expression,and this study aimed to further clarify the anti-HBV mechanism of TRIM25.Methods:The TRIM25-mediated degradation of hepatitis B virus X(HBx)protein was determined by detecting the expression of HBx in TRIM25-overexpressed or knocked-out HepG2 or HepG2-NTCP cells via Western blotting.Co-immunoprecipitation was performed to confirm the interaction between TRIM25 and HBx,and colocalization of TRIM25 and HBx was identified via immunofluorescence;HBV e-antigen and HBV surface antigen were qualified by using an enzyme-linked immunosorbent assay(ELISA)kit from Kehua Biotech.TRIM25 mRNA,pregenomic RNA(pgRNA),and HBV DNA were detected by quantitative real-time polymerase chain reaction.The retinoic acid-inducible gene I(RIG-I)and pgRNA interaction was verified by RNA-binding protein immunoprecipitation assay.Results:We found that TRIM25 promoted HBx degradation,and confirmed that TRIM25 could enhance the K90-site ubiquitination of HBx as well as promote HBx degradation by the proteasome pathway.Interestingly,apart from the Really Interesting New Gene(RING)domain,the SPRY domain of TRIM25 was also indispensable for HBx degradation.In addition,we found that the expression of TRIM25 increased the recognition of HBV pgRNA by interacting with RIG-I,which further increased the IFN production,and SPRY,but not the RING domain is critical in this process.Conclusions:The study found that TRIM25 interacted with HBx and promoted HBx-K90-site ubiquitination,which led to HBx degradation.On the other hand,TRIM25 may function as an adaptor,which enhanced the recognition of pgRNA by RIG-I,thereby further promoting IFN production.Our study can contribute to a better understanding of host-virus interaction.
