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CRISPR/Cas9-based tools for targeted genome editing and replication control of HBV

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Virologica Sinica 2015年第5期30卷 317-325页

作者： Cheng Peng mengji lu Dongliang Yang Department of Infectious Diseases Union HospitalTongji Medical CollegeHuazhong University of Science and Technology Institute of Virology University Hospital of EssenUniversity of Duisburg-Essen

Hepatitis B virus(HBV) infection remains a major global health problem because current therapies rarely eliminate HBV infections to achieve a complete cure. A different treatment paradigm to effectively clear HBV infection and eradicate latent viral reservoirs is urgently required. In recent years, the development of a new RNA-guided gene-editing tool, the CRISPR/Cas9(clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9) system, has greatly facilitated site-specific mutagenesis and represents a very promising potential therapeutic tool for diseases, including for eradication of invasive pathogens such as HBV. Here, we review recent advances in the use of CRISPR/Cas9, which is designed to target HBV specific DNA sequences to inhibit HBV replication and to induce viral genome mutation, in cell lines or animal models. Advantages, limitations and possible solutions, and proposed directions for future research are discussed to highlight the opportunities and challenges of CRISPR/Cas9 as a new, potentially curative therapy for chronic hepatitis B infection.

关键词： hepatitis B virus(HBV) CRISPR/Cas9 covalently clos

Contribution of Toll-like receptors to the control of hepatitis B virus infection by initiating antiviral innate responses and promoting specific adaptive immune responses

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Cellular & Molecular Immunology 2015年第3期12卷 273-282页

作者： Zhiyong Ma Ejuan Zhang Dongliang Yang mengji lu Institute of Virology University Hospital Essen University of Duisburg-Essen Essen Germany Department of Infectious Diseases Zhongnan Hospital ofWuhan University Wuhan China Wuhan Institute of Virology Chinese Academy of Sciences Wuhan China Department of Infectious Diseases Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China

It is well accepted that adaptive immunity plays a key role in the control of hepatitis B virus （HBV） infection. In contrast, the contribution of innate immunity has only received attention in recent years. Toll-like receptors （TLRs） sense pathogen-associated molecule patterns and activate antiviral mechanisms, including intracellular antiviral pathways and the production of antiviral effector interferons （IFNs） and pro-inflammatory cytokines. Experimental results from in vitroand in vivo models have demonstrated that TLRs mediate the activation of cellular signaling pathways and the production of antiviral cytokines, resulting in a suppression of HBV replication. However, HBV infection is associated with downregulation of TLR expression on host cells and blockade of the activation of downstream signaling pathways. In primary HBV infection, TLRs may slow down HBV infection, but contribute only indirectly to viral clearance. Importantly, TLRs may modulate HBV-specific T- and B-cell responses in vivo, which are essential for the termination of HBV infection. Thus, TLR agonists are promising candidates to act as immunomodulators for the treatment of chronic HBV infection. Antiviral treatment may recover TLR expression and function in chronic HBV infection and may increase the efficacy of therapeutic approaches based on TLR activation. A combined therapeutic strategy with antiviral treatment and TLR activation could facilitate the restoration of HBV-specific immune responses and thereby, achieve viral clearance in chronically infected HBV patients.

关键词： Hepatitis B virus Toll like receptor Innate immune response Adaptive immune response

Interconnection of cellular autophagy and endosomal vesicle trafficking and its role in hepatitis B virus replication and release

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Virologica Sinica 2024年第1期39卷 24-30页

作者： Jia Li Yong Lin Xueyu Wang mengji lu Institute for Virology University Hospital EssenUniversity of Duisburg-EssenEssen45122Germany Key Laboratory of Molecular Biology of Infectious Diseases(Chinese Ministry of Education) Chongqing Medical UniversityChongqing400016China The Key Laboratory for Diagnosis and Treatment of Infectious Diseases The First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou310000China

Hepatitis B virus(HBV)produces and releases various particle types,including complete virions,subviral particles with envelope proteins,and naked *** studies demonstrate that HBV exploits distinct intracellular membrane trafficking pathways,including the endosomal vesicle trafficking and autophagy pathway,to assemble and release viral and subviral ***,we summarize the findings about the distinct roles of autophagy and endosomal membrane trafficking and the interaction of both pathways in HBV replication,assembly,and release.

关键词： Amphisome Autophagy Endosomal vesicle Hepatitis B virus(HBV)

mTOR Signaling: The Interface Linking Cellular Metabolism and Hepatitis B Virus Replication

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Virologica Sinica 2021年第6期36卷 1303-1314页

作者： Xueyu Wang Zhiqiang Wei Yongfang Jiang Zhongji Meng mengji lu Department of Infectious Diseases The Second Xiangya HospitalCentral South UniversityChangsha 410011China Institute of Virology University Hospital EssenUniversity of Duisburg-Essen45122 EssenGermany Institute of Biomedical Research Hubei Clinical Research Center for Precise Diagnosis and Treatment of Liver CancerTaihe HospitalHubei University of MedicineShiyan 442000China Department of Infectious Diseases Taihe HospitalHubei University of MedicineShiyan 442000China

Mammalian target of rapamycin(m TOR) is a conserved Ser/Thr kinase that includes m TOR complex(m TORC) 1 and m TORC2. The m TOR pathway is activated in viral hepatitis, including hepatitis B virus(HBV) infection-induced ***, chronic HBV infection remains one of the most serious public health issues worldwide. The unavailability of effective therapeutic strategies for HBV suggests that clarification of the pathogenesis of HBV infection is urgently required. Increasing evidence has shown that HBV infection can activate the m TOR pathway, indicating that HBV utilizes or hijacks the m TOR pathway to benefit its own replication. Therefore, the m TOR signaling pathway might be a crucial target for controlling HBV infection. Here, we summarize and discuss the latest findings from model biology research regarding the interaction between the m TOR signaling pathway and HBV replication.

关键词： Mammalian target of rapamycin(mTOR) Hepatitis B virus(HBV) Metabolism Autophagy

Controversial: Early Innate Responses to Hepatitis B Virus Infection,an Explanation for Viral Persistence?

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Virologica Sinica 2021年第1期36卷 163-166页

作者： Ruth Broering Xufeng luo Jia Liu mengji lu Department of Gastroenterology and Hepatology University Hospital EssenUniversity of Duisburg-Essen45147 EssenGermany Department of Infectious Diseases Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Institute of Virology University Hospital EssenUniversity of Duisburg-Essen45147 EssenGermany

Hepatitis B virus(HBV)infection is one of the most common causes for liver related morbidity and mortality *** fibrosis and cirrhosis occur in the course of chronic HBV infection,with the increasing risk to develop hepatocellular *** about 95%of adults’acute hepatitis B virus infection is self-limited,whereas in 90%of young children HBV infection leads to chronic *** is likely that a fully developed immune system contributes to HBV clearance(Dandri and Locarnini 2012;Bertoletti and Kennedy 2015).

关键词： infection mortality acute

New therapeutic vaccination strategies for the treatment of chronic hepatitis B

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Virologica Sinica 2014年第1期29卷 10-16页

作者： Jia Liu Anna Kosinska mengji lu Michael Roggendorf Institute for Virology University Hospital of EssenUniversity of Duisburg-Essen

Chronic hepatitis B virus(CHB) is currently treated with either interferon-based or nucleot(s)idebased antiviral ***,treatment with pegylated interferon alpha results in a durable antiviral response in only about 30%patients and is associated with side *** patients receiving nucleot(s)ide analogue treatment do not establish long-term,durable control of Infection and have rebounding viremia after cessation of ***,novel therapy strategies are necessary to achieve the induction of potent and durable antiviral immune responses of the patients which can maintain long-term control of viral *** vaccination of HBV carriers is a promising strategy for the control of hepatitis *** the authors review new therapeutic vaccination strategies to treat chronic hepatitis B which may be introduced for patient treatment in the future.

关键词： hepatitis B virus woodchuck hepatitis virus therapeutic vaccination immunomodulation programmed death-1

Construction and Identification of a Human Liver Specific MicroRNA Eukaryotic Expression Vector

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Cellular & Molecular Immunology 2007年第6期4卷 473-477页

作者： Shanshan Chen Ming Ni Bing Yu Tingting Lv mengji lu Feili Gong Department of Pathogenic Biology Tongji Medical College of Huazhong University of Science ＆ Technology Wuhan 430030 China Department of Infectious Diseases Tongji Hospital Tongji Medical College of Huazhong University of Science ＆ Technology Wuhan 430030 China Department of Immunology Tongji Medical College of Huazhong University of Science ＆ Technology Wuhan 430030 China

MiR-122 is one of the non-coding RNAs which showed its effects on the lipo-metablism, virus infection and HCC forming through regulation of liver gene expression. Its eukaryotic expression vector was constructed by using pSuper which was widely applied in the siRNA expression. The precursor of human miR-122 gene was amplified by polymerase chain reaction （PCR） from the human genomic DNA. The positive clones were screened by PCR and restriction enzyme digestion. The new expression vector of miR-122 was named pHsa-m122. PHsa-m122 and its controls were transfected to HepG2 cells. The miR-122 expression activity was evaluated by GFP122i sensor reporter plasmid through fluorescence detection and Western blot. It was shown that the fluorescence intensity of GFP122si and pHsa-m122 co-transfection group was weaker than that of the controls, so the functional activity of expressed miR-122 was detected. When HepG2 cells were co-transfected with HBV1.3 and pHsa-m122 plasmids, the results showed miR-122 may down-regulate the gene expression of HBV. The human liver specific microRNA eukaryotic expression vector of miR-122 was constructed successfully, which may facilitate further study of its function in the development of liver virus infection diseases and HCC. Cellular ＆ Molecular Immunology.

关键词： miRNA miR-122 eukaryotic expression vector pSuper

Interaction of viruses with host immune system and immunomodulation in chronic viral infections

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Virologica Sinica 2014年第1期29卷 1-2页

作者： mengji lu Yumei Wen Institute for Virology University Hospital of EssenUniversity Duisburg-Essen Key Laboratory of Medical Molecular Virology of Ministries of Education and Health Shanghai MedicalCollege and Institute of Medical MicrobiologyFudan University

The WHO estimates that almost500 million people world-wide are chronically infected with hepatitis B and C viruses(HBV and HCV)and human immune deficiency virus(HIV).During the recent years,significant progress was ma... 详细信息

关键词：病毒感染慢性感染免疫调节免疫系统人免疫缺陷病毒宿主丙型肝炎病毒治疗方案

Characterization of SARS-CoV-2-specific humoral immunity and its potential applications and therapeutic prospects

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Cellular & Molecular Immunology 2022年第2期19卷 150-157页

作者： Jiaxin Zheng Yingying Deng Zhenyu Zhao Binli Mao mengji lu Yong Lin Ailong Huang Key Laboratory of Molecular Biology of Infectious Diseases(Chinese Ministry of Education) Institute for Viral HepatitisDepartment of Infectious DiseasesThe Second Affiliated HospitalChongqing Medical UniversityChongqingChina. Institute for Virology University Hospital EssenUniversity of Duisburg-EssenEssen 45122Germany

Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is an ongoing pandemic that poses a great threat to human health *** the humoral immune response plays essential roles in disease occurrence and development,understanding the dynamics and characteristics of virus-specific humoral immunity in SARS-CoV-2-infected patients is of great importance for controlling this *** this review,we summarize the characteristics of the humoral immune response after SARS-CoV-2 infection and further emphasize the potential applications and therapeutic prospects of SARSCoV-2-specific humoral immunity and the critical role of this immunity in vaccine ***,serological antibody testing based on the humoral immune response can guide public health measures and control strategies;however,it is not recommended for population surveys in areas with very low *** evidence suggests that asymptomatic individuals have a weaker immune response to SARS-CoV-2 infection,whereas SARS-CoV-2-infected children have a more effective humoral immune response than *** correlations between antibody(especially neutralizing antibody)titers and protection against SARS-CoV-2 reinfection should be further *** addition,the emergence of cross-reactions among different coronavirus antigens in the development of screening technology and the risk of antibody-dependent enhancement related to SARS-CoV-2 vaccination should be given further attention.

关键词： Antibody Humoral immunity SARS-CoV-2 Serological antibody test Vaccine