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New Gene Variants Associated with the Risk of Chronic hbv infection

Virologica Sinica 2020年第4期35卷 378-387页

作者： Mengjie Fan Jing Wang Sa Wang Tengyan Li Hong Pan Hankui Liu Huifang Xu Daria V.Zhernakova Stephen J.O’Brien Zhenru Feng Le Chang Erhei Dai Jianhua Lu Hongli Xi Yanyan Yu Jianguo Zhang Binbin Wang Zheng Zeng Department of Infectious Diseases Peking University First HospitalBeijing 100034China Department of Medical Genetics and Development Biology School of Medical BasicCapital Medical UniversityBeijing 100069China Center for Genetics National Research Institute for Family PlanningBeijing 100081China BGI-Shenzhen Shenzhen 518083China BGI Genomics BGI-ShenzhenShenzhen 518083China Laboratory of Genomic Diversity Center for Computer TechnologiesITMO UniversitySt.PetersburgRussia 197101 Guy Harvey Oceanographic Center Halmos College of Natural Sciences and OceanographyNova Southeastern UniversityFt LauderdaleFL 33004USA Department of Laboratory Medicine Peking University First HospitalBeijing 100034China The Fifth Hospital of Shijiazhuang Shijiazhuang 050024China

Some patients with chronic hepatitis B virus(hbv)infection failed to clear hbv,even persistently continue to produce antibodies to *** we performed a two stage genome wide association study in a cohort of Chinese patients designed to discover single nucleotide variants that associate with hbv infection and clearance of *** first stage involved genome wide exome sequencing of 101 cases(HBsAg plus anti-HBs positive)compared with 102 control patients(antiHBs positive,HBsAg negative).Over 80%of individual sequences displayed 209 sequence ***,uncertain bases[10%or low-quality base calls([50%)were filtered and compared to the human reference genome *** the second stage,579 chronic hbv infected cases and 439 hbv clearance controls were sequenced with selected genes from the first *** there were no significant associated gene variants in the first stage,two significant gene associations were discovered when the two stages were assessed in a combined *** association showed rs506121-“T”allele[within the dedicator of cytokinesis 8(DOCK8)gene]was higher in chronic hbv infection group than that in clearance group(P=0.002,OR=0.77,95%CI[0.65,0.91]).The second association involved rs2071676—A allele within the Carbonic anhydrase(CA9)gene that was significantly elevated in chronic hbv infection group compared to the clearance group(P=0.0003,OR=1.35,95%CI[1.15,1.58]).Upon replication these gene associations would suggest the influence of DOCK8 and CA9 as potential risk genetic factors in the persistence of hbv infection.

关键词： Whole exome sequencing hbv infection DOCK8 CA9 Variation

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GLOBAL ASYMPTOTICAL PROPERTIES FOR A DIFFUSED hbv infection MODEL WITH CTL IMMUNE RESPONSE AND NONLINEAR INCIDENCE

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Acta Mathematica Scientia 2011年第5期31卷 1959-1967页

作者：王绍利冯新龙何银年 Faculty of Science Xi'an Jiaotong University College of Mathematics and Systems Science Xinjiang University

This article proposes a diffused hepatitis B virus （hbv） model with CTL immune response and nonlinear incidence for the control of viral infections. By means of different Lyapunov functions, the global asymptotical properties of the viral-free equilibrium and immune-free equilibrium of the model are obtained. Global stability of the positive equilibrium of the model is also considered. The results show that the free diffusion of the virus has no effect on the global stability of such hbv infection problem with Neumann homogeneous boundary conditions.

关键词： hbv infection diffusion CTL immune response nonlinear incidence global asymptotical stability

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Dynamics of a diffusion-driven hbv infection model with capsids and time delay

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International Journal of Biomathematics 2017年第5期10卷 27-44页

作者： Kalyan Manna Department of Mathematics Indian Institute of Technology Guwahati Guwahati 781039 Assam India

In this paper, a diffusive hepatitis B virus （hbv） infection model with a discrete time delay is presented and analyzed, where the spatial mobility of both intracellular capsid covered hbv DNA and hbv and the intracellular delay in the reproduction of infected hepatocytes are taken into account. We define the basic reproduction number R0 that determines the dynamical behavior of the model. The local and global stability of the spatially homogeneous steady states are analyzed by using the linearization technique and the direct Lyapunov method, respectively. It is shown that the susceptible uninfected steady state is globally asymptotically stable whenever R0 ≤i and is unstable whenever R0 〉1. Also, the infected steady state is globally asymptotically stable when R0 〉 1. Finally, numerical simulations are carried out to illustrate the results obtained.

关键词： hbv infection diffusion delay global stability Lyapunov function numer- ical simulation.

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IL-6 Plays a Crucial Role in hbv infection

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Journal of Clinical and Translational Hepatology 2015年第4期3卷 271-276页

作者： Tian Lan Lei Chang Long Wu Yu-Feng Yuan Zhongnan Hospital of Wuhan University Department of Hepatobiliary SurgeryWuhan UniversityWuhanChina

Interleukin-6(IL-6),a cytokine mainly produced by activated monocytes,has broad pleiotropic actions that affect the functions of a variety of lymphoid *** roles of IL-6 in regulating immunity to infections are currently being ***,IL-6-mediated cellular and humoral immune responses play a crucial role in determining the outcome of viral *** article reviews the current knowledge on the critical role of IL-6 in hepatitis B virus(hbv)*** a competent intermediary,IL-6 derived from activated monocytes plays an important role in promoting lymphocytes responses that are essential for effective viral ***,as a mediator of inflammation,IL-6 is also involved in the development of hbv-induced liver cirrhosis and exacerbating liver ***,the current data point to IL-6 as an immunoregulatory cytokine in hbv *** strategies aimed at optimizing the beneficial effects of IL-6 in hbv infection may prove to be an ordeal in the future,as they should foster the strengths of IL-6 while circumventing potential drawbacks.

关键词： Interleukin-6 hbv infection Immunoregulation

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Synergistic Action of Clonorchiasis,hbv infection and Alcohol Consumption on Primary Hepatocellular Carcinoma

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Chinese Journal of Clinical Oncology 2009年第2期6卷 104-112页

作者： Shengkui Tan Xiaoqiang Qiu Hongping Yu Xiaoyun Zeng Zengming Xiao Lequn Li Qiuan Zhong Department of Preventative Medicine Guilin Medical ColLege Guilin 541001 Guangxi Zhuang Autonomous Region China Department of Epidemiology School of Public Health Guangxi Medical University Nanning 530021 Guangxi Zhuang Autonomous Region China Department of Hepatobiliary Surgery The First Hospital of Guangxi Medical UniversityNanning 530021 Guangxi Zhuang Autonomous Region China

OBJECTIVE It has been recognized that hbv infection and alcohol consumption are two important risk factors for primary hepatocellular carcinoma （HCC）. Recently, the role of clonorchiasis as a risk factor for HCC is controversial. We aimed to investigate whether these factors increase the risk of HCC in Guangxi, China. METHODS A hospital-based, case-control study of HCC was conducted from July 2005 to July 2007. We enrolled 500 consecutive patients with HCC as an experimental group and 500 patients without tumor in liver as a control group. The risk factors that the patients were exposed to were assessed. RESULTS Comparing the risks of developing the HCC, we found out the following results. The risk of developing HCC for the patients with clonorchiasis was 5 folds of that for the patients without clonorchiasis （OR = 5.0; 95% CI： 3.1-8.1）, and the risk for the patients with alcohol consumption was 3 folds of that for the patients without drinking alcohol （OR = 3.4; 95% CI： 2.3-4.9）, and similarly, the risk for the patients with hbv infection was 21 times of that for the patients without hbv infection （OR = 20.6; 95% CI： 14.3-29.7）. According to crossover analysis, there was significant interaction among clonorchiasis, hbv infection and alcohol consumption, with synergistic indices greater than 1. The etiologic fractions attributed to these interactions [EF （A × B）] are 0.7465, 0.5789 and 0.5506, respectively. CONCLUSION Clonorchiasis, hbv infection and heavy alcohol consumption are independent risk factors for developing HCC in our population in Guangxi, and as they can interact synergistically, the risk of developing HCC is increased. Data from this study may indicate new prevention strategies of developing HCC in high-risk individuals.

关键词： primary hepatocellular carcinoma risk factor clonorchiasis hbv infection alcohol consumption synergistic action.

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A murine CXCR3+CXCR6+ γδT cell subset resides in liver and protects from hbv infection

A murine CXCR3+CXCR6+ γδT cell subset resides in liver and...

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第十四届全国免疫学学术大会

作者： Yanan Wang Yun Guan Yuan Hu Yan Li Nan Lu Cai Zhang Institute of Immunopharmaceutical Sciences School of Pharmaceutical SciencesCheeloo College of MedicineShandong University Jining NO.1 People's Hospital Institute of Biomedical Sciences College of Life SciencesShandong Normal University Institute of Diagnostics School of MedicineCheeloo College of MedicineShandong University

γδT cells belong to innate immune system and are regarded as the first line of defense in infection and tumor.γδT cells are defined as tissue-resident lymphocytes in skin,lung and intestinal *** are relatively abundant in ***,little is known about the residency of hepatic γδT *** comparing the phenotype of murine γδT cells in liver,spleen,thymus and small intestine,we found a CXCR3CXCR6γδT cell subset with tissue-resident characteristics,specifically existed in liver from embryo to *** sinusoidal endothelium cells mediated the retention of CXCR3CXCR6γδT cells by the interaction between CXCR3,CXCR6 and their *** acute hbv infection,CXCR3CXCR6+γδT cells produced high levels of IFN-γ,and adoptive transferring of CXCR3CXCR6γδT cells into acute hbv infected TCRδ mice could efficiently decrease the level of HBsAg and *** suggests that the liver-resident CXCR3CXCR6γδT cells play a protective role during acute hbv *** expanding and activating liver-resident CXCR3CXCR6γδT cells in vivo or in vitro may have great application prospects in the immunotherapy of acute hbv infection.

关键词： Liver γδT cells residency liver-resident γδT cells Chemotaxis hbv infection

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High Throughput RNAi screening for epigenetic factors in IFNα therapy of hbv infection

High Throughput RNAi screening for epigenetic factors in IFN...

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第十一届全国免疫学学术大会

作者： Chen Kun Liu Juan Xia Meng Liu Shuxun Han Dan Wang Chunmei Cao Xuetao Institute of Immunology Zhejiang University School of Medicine National Key Laboratory of Medical Immunology & Institute of Immunology Second Military Medical University National Key Laboratory of Medical Molecular Biology & Department of Immunology Chinese Academy of Medical Sciences

Interferon-α(IFNα) is an important and available drug for hbv treatment, however, the long-term efficiency of IFNα therapy in chronic hbv patients remain limited. Epigenetic modification plays critical roles in multiple biological process through regulating gene expression, however, it remains poorly understood how epigenetic factors regulate IFN-me-diated antiviral immunity. Herein, we performed a non-biased high-throughput RNAi screening(HTS) to identify epigenetic regulators that inhibit hbv replication in combination with IFNα. HepG2.215 cells(hbv positive) were transfected with a library of small hairpin RNAs(shRNAs) targeting 711 known epigenetic regulators and then treated with IFNα. Cells supernatants were collected and analyzed for HBsAg secretion by ELISA. This primary RNAi screening identified 18 epigenetic genes that prevented HBsAg secretion and 28 genes that promoted HBsAg secretion in response to IFNα treatment. In order to exclude the off-target effect from shRNAs, we designed three individual non-smsiRNAs targeting the primary hits for further validation. 14 out of the 18 epigenetic genes were validated to inhibit HBsA g secretion. The validated hits included NCOA1, which is a member of the p160/steroid receptor coactivator(SRC) family and has histone acetyltransferase activity. Further studies by overexpression of NCOA1 in HepG 2.2.15 cells and HepG 2 cells transfected with hbv1.3 plasmid confirmed its inhibitory role in hbv infection. Our results highlight the utility of RNAi screening for identifying epigenetic genes regulating IFNα antiviral activity and outline potential strategies for optimizing IFNα therapy.

关键词： IFNα epigenetic high-throughput RNAi screening hbv infection

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Discovery of a novel sodium taurocholate cotransporting polypeptide(NTCP) inhibitor: Design, synthesis, and anti-proliferative activities

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Chinese Chemical Letters 2020年第6期31卷 1422-1426,F0003页

作者： Honggang Xiang Yanmei Chen Jifa Zhang jin Zhang Dabo Pan Bo Liu Liang Ouyang State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan UniversityCollaborative Innovation Center for BiotherapyChengdu 610041China Institute of Traditional Chinese Medicine&Natural Products Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs ResearchCollege of PharmacyJinan UniversityGuangzhou 510632China

Sodium taurocholate cotransporting polypeptide(NTCP)is identified as the functional receptor for hbv entry,which is responsible for upregulated hbv transcription in the hbv life ***,NTCP is also implicated in the progression of hbv-induced hepatocellular carcinoma(HCC).Thereby,NTCP-targeting entry inhibitors are proposed to suppress hbv infection and replication in hbv-induced hepatoma ***,we integrated in silico screening and chemical synthesis to obtain a small-molecule NTCP inhibitor B7,which exhibited moderate anti-proliferative activities against HepG2 cells and anti-hbv activity in ***,CETSA assay,molecular docking,and MD simulation validated that B7 could bind to ***,western blot analysis demonstrated that B7 induced apoptosis with an increased expression of Bax and caspase 3 cleaving as well as a decreasing expression of Bcl-2 in HepG2 *** together,our study identified B7 as a novel NTCP inhibitor with anti-proliferation activities which might provide a new opportunity for HCC therapy.

关键词： Sodium taurocholate cotransporting polypeptide (NTCP) Hepatocellular carcinoma(HCC) hbv infection NTCP inhibitor Apoptosis

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乙型肝炎病毒感染与原发性肝癌关系的血清流行病学研究

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西安交通大学学报(医学版) 1988年第1期 44-48页

作者：唐晓红徐慧文西安医科大学流行病学研究室

本文采用血清流行病学方法探讨了hbv感染与原发性肝癌的关系。肝癌病人HB_SAg和抗-HB_C阳性率明显高于对照组,而抗-HB_S则相反;肝硬化hbv感染模式非常接近于肝癌,hbv总感染率在肝癌和对照组间无显著性差别。结果提示hbv感染与原发性肝... 详细信息

本文采用血清流行病学方法探讨了hbv感染与原发性肝癌的关系。肝癌病人HB_SAg和抗-HB_C阳性率明显高于对照组,而抗-HB_S则相反;肝硬化hbv感染模式非常接近于肝癌,hbv总感染率在肝癌和对照组间无显著性差别。结果提示hbv感染与原发性肝癌有一定联系,但非单一联系。

关键词： hbv infection Primary Liver cirrhosis AFP

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Seroprevalence of Hepatitis B Virus (hbv) among Voluntary Healthy Blood Donors at Tellewonyan Memorial Hospital Voinjama, Lofa County, Liberia

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Journal of Biosciences and Medicines 2021年第8期9卷 113-119页

作者： Ezekiel Kanue Fardolo Emmanuel Timothy Cooper Caroline Nyawira Wahome Jean K. Kaly Junior S. Puiyoe Department of Medical Laboratory Science School of Medicine Kenyatta University Nairobi Kenya Department of Medical Laboratory Science Mother Patern College of Health Sciences Stella Maris Polytechnic University Monrovia Liberia USAID Infectious Diseases Research Monrovia Liberia Department of Biochemistry Microbiology and Biotechnology Kenyatta University Nairobi Kenya Medical Department Telewonyan Memorial Hospital Lofa Liberia

Background: The prevalence of transfusion associated hepatitis B virus (hbv) infection differs across different population geographically. Ascertaining the seroprevalence of hbv infection is vital to informing the way of precautionary and control strategies. This study sought to establish the seroprevalence of hepatitis B surface antigen (hbvsAg) among blood donors in Yelewonyan Memorial Hospital Lofa, Liberia. Methods: This was a retrospective study which involved reviewing of blood donation records for the year 2020 at Telewonyan Memorial Hospital in Lofa County. The data obtained from the records were analyzed. Data analysis was done using SPSS version 12 for windows. Results: A total of 584 voluntary blood donors were screened for donation in 2020. Out of 584, 554 (95.9%) were males while the rest were females. Prevalence of 3.3% was observed among blood donors in Telewonyan Memorial Hospital. There is a significant difference between gender and age with hbv seropositivity among blood donors. Conclusion: The findings of this study suggest that the study site is of low endemicity with hbv infection. Usually, males are more probably to be hbvsAg seropositive than their female’s counterpart. Planning more extensive study and educational programs would help minimize the spread of hbv infection among the general population.

关键词： Liberia Blood Donors Seropositivity hbv infection Blood Transfusion Lofa

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