2.TRIM25 inhibits HBV replication by promoting HBx degradation and the RIG-I-mediated pgRNA recognition.
Hongxiao SONG ; Qingfei XIAO ; Fengchao XU ; Qi WEI ; Fei WANG ; Guangyun TAN
Chinese Medical Journal 2023;136(7):799-806
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.
Humans
;
Hepatitis B virus
;
DEAD Box Protein 58/metabolism*
;
RNA
;
Liver Neoplasms
;
Virus Replication
;
Tripartite Motif Proteins/genetics*
;
Transcription Factors
;
Ubiquitin-Protein Ligases/genetics*
3.Research progress on the comorbidity between hepatitis B virus infection and noncommunicable diseases.
Jin Zhao XIE ; Tian Yi LI ; Lu Xin ZHENG ; Sen Yao CAI ; Jing GU ; Yuan Tao HAO
Chinese Journal of Preventive Medicine 2023;57(9):1523-1528
With the decline in hepatitis B virus (HBV) incidence and the increase in the life expectancy of infected individuals, the population infected with HBV is experiencing rapid aging, leading to an escalating risk of co-morbid chronic noncommunicable diseases (NCDs). This study summarizes research related to the comorbidity between HBV and NCDs, discussing the aging of the HBV-infected population, the mechanisms, prevalence, and management of this comorbidity. This study provides insights into potential directions for future research on the comorbidity between HBV and NCDs and aims to provide a basis for further research and the development of prevention and treatment strategies for the comorbidity of NCDs among HBV-infected individuals in China.
Humans
;
Hepatitis B virus
;
Noncommunicable Diseases/epidemiology*
;
Hepatitis B/epidemiology*
;
Comorbidity
;
China/epidemiology*
4.Analysis of the reentry status of blood donors with reactive bloodborne pathogen screening markers in Hangzhou City.
Ying LU ; Wei DING ; Wen Yan GUO ; Fa Ming ZHU ; Jun ZHANG
Chinese Journal of Preventive Medicine 2023;57(10):1565-1570
<b>Objective:b> To explore the reentry rate of reactive blood donors in the bloodborne pathogen infection screening in Hangzhou City, and analyze the donation behavior of those who successfully returned. <b>Methods:b> A retrospective analysis of the return data of blood donors with reactive bloodborne pathogen screening markers was conducted at Zhejiang Provincial Blood Center from June 2017 to May 2022. The reentry process for blood donors with reactive bloodborne pathogen screening markers in Hangzhou City is as follows: after the initial screening period of 6 months, donors can voluntarily apply for return to the blood center. Samples are collected and subjected to routine enzyme-linked immunosorbent assay (ELISA) screening for HBsAg, anti-HCV, HIV Ab/Ag, and anti-TP, as well as a single nucleic acid (HIV/HCV/HBV) test. For samples that show non-reactivity in both ELISA and nucleic acid tests, serum biomarker testing for the reasons of exclusion is performed using chemiluminescence immunoassay (CLIA), and those with non-reactivity are allowed to return. <b>Results:b> A total of 4 583 reactive blood donors who met the criteria for re-entry applied for reentry, out of which 475 applications were received from donors in the Hangzhou area. Among these, 279 donors were successfully readmitted, resulting in a success rate of 58.74% (279/475). By the end of December 2021, out of the 174 donors who successfully returned, 114 donors chose to donate again. They collectively donated 39 530 ml of whole blood and 1 147.2 therapeutic doses of platelets. Among these, 21 donors once again showed reactivity for pathogen infection biomarkers, accounting for 18.42% (21/114). <b>Conclusion:b> The reentry strategy has somewhat mitigated the attrition of blood donors. Nevertheless, there are instances where donors who were successfully readmitted show reactivity once more in the screening for pathogen infection biomarkers.
Humans
;
Blood Donors
;
Blood-Borne Pathogens
;
Retrospective Studies
;
Mass Screening/methods*
;
Biomarkers
;
HIV Infections
;
Nucleic Acids
;
Hepatitis B virus
5.Anti-hepatitis B virus activities of natural products and their antiviral mechanisms.
Wanyu DENG ; Fu CHEN ; Yue ZHAO ; Ming ZHOU ; Min GUO
Chinese Journal of Natural Medicines (English Ed.) 2023;21(11):803-811
Chronic hepatitis B (CHB) infections caused by the hepatitis B virus (HBV) continue to pose a significant global public health challenge. Currently, the approved treatments for CHB are limited to interferon and nucleos(t)ide analogs, both of which have their limitations, and achieving a complete cure remains an elusive goal. Therefore, the identification of new therapeutic targets and the development of novel antiviral strategies are of utmost importance. Natural products (NPs) constitute a class of substances known for their diverse chemical structures, wide-ranging biological activities, and low toxicity profiles. They have shown promise as potential candidates for combating various diseases, with a substantial number demonstrating anti-HBV properties. This comprehensive review focuses on the current applications of NPs in the fight against HBV and provides a summary of their antiviral mechanisms, considering their impact on the viral life cycle and host hepatocytes. By offering insights into the world of anti-HBV NPs, this review aims to furnish valuable information to support the future development of antiviral drugs.
Humans
;
Hepatitis B virus
;
Hepatitis B, Chronic/drug therapy*
;
Antiviral Agents/therapeutic use*
;
Biological Products/therapeutic use*
;
Hepatocytes
7.Incidence and factors associated with hepatitis B surface antigen seroclearance in patients co-infected with HBV/HIV during antiretroviral therapy in Guangdong, China.
Yaozu HE ; Weiyin LIN ; Hong LI ; Fei GU ; Huolin ZHONG ; Yun LAN ; Yonghong LI ; Pengle GUO ; Fengyu HU ; Weiping CAI ; Xiaoping TANG ; Linghua LI
Chinese Medical Journal 2023;136(22):2686-2693
BACKGROUND:
Hepatitis B surface antigen (HBsAg) clearance is vital for a functional cure of hepatitis B virus (HBV) infection. However, the incidence and predictors of HBsAg seroclearance in patients co-infected with HBV and human immunodeficiency virus (HIV) remain largely unknown in Guangdong, China.
METHODS:
Between 2009 and 2019, patients co-infected with HBV/HIV undergoing antiretroviral therapy (ART) in Guangzhou Eighth People's Hospital affiliated to Guangzhou Medical University were retrospectively reviewed with the endpoint on December 31, 2020. The incidence and risk factors for HBsAg seroclearance were evaluated using Kaplan-Meier and multivariate Cox regression analyses.
RESULTS:
A total of 1550 HBV/HIV co-infected patients were included in the study, with the median age of 42 years and 86.0% (1333/1550) males. Further, 98.3% (1524/1550) received ART containing tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC). HBV DNA was examined in 1283 cases at the last follow-up. Over the median 4.7 years of follow-up, 8.1% (126/1550) patients achieved HBsAg seroclearance, among whom 50.8% (64/126) obtained hepatitis B surface antibody, 28.1% (137/488) acquired hepatitis B e antigen seroconversion, and 95.9% (1231/1283) undetectable HBV DNA. Compared with patients who maintained HBsAg positive, cases achieving HBsAg seroclearance showed no differences in age, gender, CD4 + T cell count, alanine aminotransferase (ALT) level, or fibrosis status; however, they presented lower HBV DNA levels, lower HBsAg levels, and higher rates of HBV genotype B at the baseline. Multivariate analysis showed that baseline HBsAg <1500 cutoff index (COI) (adjusted hazard ratio [aHR], 2.74, 95% confidence interval [95% CI]: 1.48-5.09), ALT elevation >2 × upper limit of normal during the first six months after receiving ART (aHR, 2.96, 95% CI: 1.53-5.77), and HBV genotype B (aHR, 3.73, 95% CI: 1.46-9.59) were independent predictors for HBsAg seroclearance (all P <0.01).
CONCLUSIONS
Long-term TDF-containing ART has high anti-HBV efficacy including relatively high overall HBsAg seroclearance in HBV/HIV co-infected patients. Lower baseline HBsAg levels, HBV genotype B, and elevated ALT levels during the first six months of ART are potential predictors of HBsAg seroclearance.
Male
;
Humans
;
Adult
;
Hepatitis B Surface Antigens
;
Hepatitis B virus/genetics*
;
HIV Infections/drug therapy*
;
HIV
;
DNA, Viral
;
Incidence
;
Coinfection/drug therapy*
;
Retrospective Studies
;
Tenofovir/therapeutic use*
;
Lamivudine/therapeutic use*
;
Hepatitis B, Chronic/drug therapy*
8.Research progress of biomarkers of hepatitis B virus and clinical significance.
Xin WANG ; Xiaoqiong TANG ; Ning HAN ; Hong TANG
Journal of Biomedical Engineering 2023;40(6):1242-1248
The infection of Hepatitis B virus (HBV) can result in severe consequences, including chronic hepatitis, liver fibrosis, cirrhosis, and even liver cancer. Effective antiviral treatment has the potential to slow down the progression of the disease. HBV serum biomarkers play a crucial role in the dynamic management of chronic hepatitis B (CHB) patients. However, the conventional hepatitis B virus markers, such as hepatitis B serologic testing and HBV DNA, are insufficient to meet the clinical requirements. This review provided a comprehensive overview of the current research on the quantification of HBsAg and anti-HBc, HBV RNA and HBV core-associated antigen, which summarized the crucial role these markers play in the administration of antiviral medications, predicting the efficacy of treatment and anticipating the likelihood of virologic rebound following drug cessation, as well as assessing disease progression in CHB patients.
Humans
;
Hepatitis B virus/genetics*
;
Clinical Relevance
;
Hepatitis B, Chronic/drug therapy*
;
Hepatitis B Core Antigens/therapeutic use*
;
Biomarkers
;
Liver Cirrhosis/drug therapy*
;
Antiviral Agents/therapeutic use*
;
Hepatitis B Surface Antigens/therapeutic use*
;
DNA, Viral/therapeutic use*
;
Hepatitis B e Antigens/therapeutic use*
;
Hepatitis B/drug therapy*
9.Epidemiological survey of hepatitis B and analysis of hepatitis B vaccine coverage rate among children aged 1-14 years in Lhasa in 2006, 2014 and 2020.
Yong Hong HU ; Zhu Duo Ji DUOJI ; Qian LI ; Li Ping DENG ; Sang Zhuo Ma GONGSANG ; Bai SUO ; Zhen PU ; Tian TIAN ; Ren De Ji DEJI ; Zhen QIONG
Chinese Journal of Preventive Medicine 2023;57(3):406-410
In 2006, 2014 and 2020, the positive rates of HBsAg in 560, 384 and 402 children aged 1 to 14 years were 4.5%, 2.6% and 2.5%, respectively, with no statistically significant differences (P>0.05). The positive rate of anti-HBs was highest in 2014 (57.8%) and lowest in 2006 (34.1%) (P<0.05). The positive rate of anti-HBc was highest in 2006 (15.7%), and decreased in 2014 (7.8%) and 2020 (5.7%) (P<0.001). The timely rate of the first dose of hepatitis B vaccine for children in Lhasa in 2006, 2014 and 2020 was 7.7% (43/560), 50.3% (193/384) and 94.8% (381/402), respectively. The overall vaccination rates were 15.4% (86/560), 35.2% (135/384) and 96.0% (386/402), respectively, showing a trend of gradual increases (χtrend values were 718.63 and 589.59, both P values<0.001).
Child
;
Humans
;
Hepatitis B Vaccines
;
Hepatitis B/prevention & control*
;
Hepatitis B Surface Antigens
;
Hepatitis B virus
;
Hepatitis B Antibodies
;
Vaccination
10.Association between physical exercise and non-alcoholic fatty liver disease in people infected with hepatitis B virus.
Huan Le CAI ; Zhi Cheng DU ; Ying WANG ; Shu Ming ZHU ; Jing Hua LI ; Wang Jian ZHANG ; Jing GU ; Yuan Tao HAO
Chinese Journal of Epidemiology 2023;44(3):445-451
Objective:b> To investigate the association between physical exercise and non-alcoholic fatty liver disease (NAFLD) in people infected with HBV. Methods:b> The information about the 3 813 participants infected with HBV, including the prevalence of NAFLD, prevalence of physical exercise and other covariates, were collected from the National Science and Technology Major Project of China during 2016-2020. The logistic regression model was used to evaluate the association between physical exercise and NAFLD in HBV infected patients, and subgroup analysis was performed to identify the effect modifiers. Results:b> A total of 2 259 HBV infected participants were included in the final analysis and 454 (20.10%) had NAFLD. After adjusting for covariates, we found that moderate physical exercise was a protective factor for NAFLD (OR=0.66, 95%CI: 0.46-0.94). Subgroup analysis suggested that the protective effect of moderate physical exercise on NAFLD might be stronger in women (OR=0.61, 95%CI: 0.36-1.01), those <45 years old (OR=0.24, 95%CI: 0.06-0.80), those who had low education level (OR=0.16, 95%CI: 0.04-0.49), those who had low annual income (OR=0.39, 95%CI: 0.16-0.89 for <30 000 yuan RMB; OR=0.64, 95%CI: 0.40-1.00 for 30 000-80 000 yuan RMB), those who had hypertension (OR=0.45, 95%CI: 0.21-0.88), those with BMI ≥24.0 kg/m2 (OR=0.66, 95%CI: 0.43-1.01), those who had more daily fruit or vegetable intake (OR=0.61, 95%CI: 0.38-0.97), those who had more daily meat intake (OR=0.49, 95%CI: 0.23-0.97), and those who had no smoking history (OR=0.66, 95%CI: 0.45-0.95) or passive smoking exposure (OR=0.61, 95%CI: 0.37-0.97). Conclusions:b> Among HBV infected patients, moderate physical exercise was negatively associated with the prevalence of NAFLD. Women, young people, those who had low education level, those who had low annual income, those with hypertension, those with high BMI, those who had more daily fruit or vegetable and meat intakes, and those who had no smoking history or passive smoking exposure might be more sensitive to the protective effect.
Humans
;
Female
;
Adolescent
;
Middle Aged
;
Non-alcoholic Fatty Liver Disease/epidemiology*
;
Hepatitis B virus
;
Risk Factors
;
Tobacco Smoke Pollution
;
Exercise
;
Hypertension

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