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Clinical Manifestation and Laboratory Characteristics of SARS-CoV-2Infection in Pregnant Women

Virologica Sinica 2020年第3期35卷 305-310页

作者： chunchen wu Wenzhong Yang Xiaoxue wu Tianzhu Zhang Yaoyao Zhao Wei Ren Jianbo Xia Department of Laboratory Medicine Maternal and Child Health Hospital of Hubei ProvinceWuhan 430070China Department of Radiology Maternal and Child Health Hospital of Hubei ProvinceWuhan 430070China Department of Obstetrics Maternal and Child Health Hospital of Hubei ProvinceWuhan 430070China

The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) epidemic has become a major challenge to public health in China and other countries, considering its pathogenicity across all age groups. Pregnancy is a unique physiological condition, and is characterized by altered immunity and elevated hormone levels to actively tolerate the semiallogeneic fetus, which undergoes a sudden and substantial fluctuation during the immediate postpartum period. Changes in clinical features, laboratory characteristics, and imaging features of pregnant women during the pre-partum and postpartum periods require further elucidation. Here, we retrospectively analyzed the clinical features, laboratory characteristics, and imaging features of eight pregnant cases of SARS-CoV-2 infection during the pre-partum and post-partum periods. Our results showed that four of the eight pregnant women were asymptomatic before delivery but became symptomatic post-partum. Correspondingly, white blood cell(WBC) counts increased and lymphocyte(LYMPH) counts decreased. C-reactive protein(CRP) levels in the serum also increased to a higher level than those in general ***, it is imperative to closely monitor laboratory parameters including the WBC count, LYMPH count, and CRP,along with other imaging features in chest CT scans, to promptly prevent, diagnose, and treat a SARS-CoV-2 infection during pregnancy.

关键词： SARS-CoV-2 Pregnant women Clinical manifestation Laboratory characteristics Immunity

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HBV sL13H mutation impairs its surface antigen expression and ability to induce autophagy

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Genes & Diseases 2022年第6期9卷 1401-1404页

作者： Jianbo Xia Liang Cao Zhenyu Zhao Yingying Deng Mengji Lu chunchen wu Yong Lin Department of Laboratory Medicine Maternal and Child Health Hospital of Hubei ProvinceTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430070PR China Department of Microbiology and Immunology Feinberg School of MedicineNorthwestern UniversityChicagoIL 60208USA Key Laboratory of Molecular Biology of Infectious Diseases(Chinese Ministry of Education) Chongqing Medical UniversityChongqing 400016PR China Institute of Virology University Hospital EssenUniversity of Duisburg-Essen47048 DuisburgGermany

Autophagy,a conserved“self-eating”process for cellular homeostasis,plays a crucial role in the hepatitis B virus(HBV)life cycle,including viral assembly,envelopment,release,and degradation.1 Autophagy can also be hijacked by HBV for its persistence and ***,the association between HBV mutations and autophagy remains ***,we found that an HBV surface antigen(HBsAg)mutation involving sL13H substitution impaired HBsAg expression and caused its abnormal distribution in vitro and in a hydrodynamic injection(HI)-based mouse model for acute HBV *** sL13H mutation also decreased autophagosome formation and inhibited autophagic *** mechanistic analysis revealed that sL13H suppresses HBV-induced autophagy initiation by inhibiting the eukaryotic translation initiation factor 2 alpha kinase 3(EIF2AK3/PERK)eeukaryotic translation initiation factor 2 subunit alpha(EIF2S1/eIF2a)eautophagy related(ATG)5/12 ***,our findings reveal a potential role for HBV mutations in manipulating host autophagic flux for virus persistence and pathogenesis in chronic hepatitis B.

关键词： impaired inhibited homeostasis

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Phosphatidylserine-Specific Phospholipase A1 is the Critical Bridge for Hepatitis C Virus Assembly

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Virologica Sinica 2019年第5期34卷 521-537页

作者： Qi Yang Min Guo Yuan Zhou Xue Hu Yun Wang chunchen wu Min Yang Rongjuan Pei Xinwen Chen Jizheng Chen Department of Gastroenterology Guangzhou Women and Children's Medical CenterGuangzhou 510623China State Key Laboratory of Virology Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China School of Life Science and Technology China Pharmaceutical UniversityNanjing 210009China

The phosphatidylserine-specific phospholipase A1(PLA1A)is an essential host factor in hepatitis C virus(HCV)*** this study,we mapped the E2,NS2 and NS5A involved in PLA1A interaction to their lumenal domains and membranous parts,through which they form oligomeric protein complexes to participate in HCV *** regions of PLA1A were involved in their interaction and complex ***,the results represented structures with PLA1A and E2 in closer proximity than NS2 and NS5A,and strongly suggest PLA1 A-E2,s physical interaction in ***,we mapped the NS5A sequence which participated in PLA1A interaction with the C-terminus of domain ***,these amino acids in the sequence are also essential for viral RNA *** experiments revealed that these four proteins interact with each ***,PLA1A expression levels were elevated in livers from HCV-infected *** conclusion,we exposed the structural determinants of PLA1A,E2,NS2 and NS5A proteins which were important for HCV assembly and provided a detailed characterization of PLA1A in HCV assembly.

关键词： Phosphatidylserine-specific phospholipase A1(PLA1 A) HCV assembly Viral RNA replication

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Enhanced host immune responses in presence of HCV facilitate HBV clearance in coinfection

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Virologica Sinica 2022年第3期37卷 408-417页

作者： Shuhui Liu Kaitao Zhao Xi Su Xiaoxiao Gao Yongxuan Yao Ranran Kong Yun Wang chunchen wu Mengji Lu Xinwen Chen Rongjuan Pei Center for Biosafety Mega-Science State Key Laboratory of VirologyWuhan Institute of VirologyChinese Academy of SciencesWuhan430071China University of Chinese Academy of Sciences Beijing100049China Department of Thoracic Surgery The Second Affiliated Hospital of Medical SchoolXi'an Jiaotong UniversityXi'an710004China Department of Medicine Icahn School of Medicine at Mount SinaiNew York10029USA Institute of Virology University Hospital EssenUniversity of Duisburg-EssenEssen45147Germany Guangzhou Laboratory Guangzhou510005China Current address:Division of Infectious Diseases Department of MedicineIcahn School of Medicine at Mount SinaiNew York10029USA Current address:State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology School of Basic Medical SciencesWuhan UniversityWuhan430071China Current address:Henan Mental Hospital the Second Affiliated Hospital of Xinxiang Medical UniversityXinxiang453002China Current address:Joint Center of Translational Precision Medicine Guangzhou Institute of PediatricsGuangzhou Women and Children Medical CenterGuangzhou510623China Current address:Department of Laboratory Medicine Maternal and Child Health Hospital of Hubei ProvinceTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Hepatitis B virus(HBV)/Hepatitis C virus(HCV)coinfection is frequently observed because of the common infection *** the reciprocal inhibition exerted by HBV and HCV genomes,the coinfection of HBV and HCV is associated with more severe forms of liver ***,the complexity of viral interference and underlying pathological mechanism is still *** the demonstration of absence of direct viral interplay,some in vitro studies suggest the indirect effects of viral-host interaction on viral dominance ***,we comprehensively investigated the viral replication and host immune responses which might mediate the interference between viruses in HBV/HCV coinfected Huh7-NTCP cells and immunocompetent HCV human receptors transgenic ICR *** found that presence of HCV significantly inhibited HBV replication in vitro and in vivo irrespective of the coinfection order,while HBV did not affect HCV *** alteration was coincidently reproduced in coinfected *** addition to the participation of innate immune response,an involvement of HCV in up-regulating HBV-specific immune responses was described to facilitate HBV *** systems partially recapitulate HBV/HCV coinfection and unveil the uncharacterized adaptive anti-viral immune responses during coinfection,which renews the knowledge on the nature of indirect viral interaction during HBV/HCV coinfection.

关键词： Hepatitis B virus(HBV) Hepatitis C virus(HCV) Coinfection Viral-host interaction Immunocompetent mouse model Adaptive immune responses

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Hepatitis B virus is degraded by autophagosome-lysosome fusion mediated by Rab7 and related components

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Protein & Cell 2019年第1期10卷 60-66页

作者： Yong Lin chunchen wu Xueyu Wang Thekla Kemper Anthony Squire Matthias Gunzer Jiming Zhang Xinwen Chen Mengji Lu Institute of Virology University Hospital EssenUniversity of Duisburg-Essen45117 EssenGermany State Key Laboratory of Virology Wuhan Institute of VirologyChinese Academy of ScienceWuhan 430071China Institute for Experimental Immunology and Imaging University Hospital EssenUniversity Duisburg-Essen45117 EssenGermany Department of Infectious Diseases Huashan HospitalFudan UniversityShanghai 200040China

Dear Editor,With an estimated 240 million chronically infected people worldwide,hepatitis B virus(HBV)infection is a major public health problem(Schweitzer et al.,2015).Despite more than 30 years of in tense research,... 详细信息

关键词： Editor people HBV

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Complementation of Wild-Type and Drug-Resistant Hepatitis B Virus Genomes to Maintain Viral Replication and Rescue Virion Production under Nucleos(t)ide Analogs

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Virologica Sinica 2019年第4期34卷 377-385页

作者： chunchen wu Baolin Li Xiaoyong Zhang Kaitao Zhao Yingshan Chen Yifei Yuan Yan Liu Rongjuan Chen Dongping Xu Xinwen Chen Mengji Lu Department of Laboratory Medicine Maternal and Child Health Hospital of Hubei ProvinceTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430070China State Key Lab of Virology Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China Institute of Virology University Hospital of Essen45122 EssenGermany University of Chinese Academy of Sciences Beijing 100049China Institute of Infectious Diseases and Liver Failure Research Center Beijing 302 HospitalBeijing 100039China

As the open reading frames of hepatitis B virus(HBV)genomes are overlapping,resistance mutations(MTs)in HBV polymerase may result in stop codon MTs in hepatitis B surface proteins,which are usually detected as a mixed population with wild-type(WT)*** question was raised how the coexistence of nucleos(t)ide analogs(NAs)resistance MTs and WT sequences affects HBV *** the present study,HBV genomes with frequently detected reverse transcriptase(RT)/surface truncation MTs,rtA181T/sW172^*,rtV191I/sW182^*and rtM204I/sW196^*,were phenotypically characterized alone or together with their WT counterparts in different ratios by transient transfection in the absence or presence of *** the absence of Nas,RT/surface truncation MTs impaired the expression and secretion of HBV surface proteins,and had a dose-dependent negative effect on WT HBV virion ***,in the presence of Nas,coexistence of MTs with WT maintained viral replication,and the presence of WT was able to rescue the production of MT HBV *** findings reveal that complementation of WT and MT HBV genomes is highly effective under drug treatment.

关键词： Hepatitis B virus(HBV) Viral replication Nucleos(t)ide analogs resistance mutations Surface truncation mutation

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Productive HBV infection of well-differentiated, hNTCP-expressing human hepatoma-derived(Huh7) cells

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Virologica Sinica 2017年第6期32卷 465-475页

作者： Ming Zhou Kaitao Zhao Yongxuan Yao Yifei Yuan Rongjuan Pei Yun Wang Jizheng Chen Xue Hu Yuan Zhou Xinwen Chen chunchen wu State Key Laboratory of Virology Wuhan Institute of Virology Chinese Academy of Sciences Shenzhen Xenotransplantation Research and Development Center State and Local Joint Cancer Genome Clinical Application of Key Technology Laboratory Shenzhen Second People's Hospital First Affiliated Hospital of Shenzhen University Institute of Immunology Zhongshan School of Medicine Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology Sun Yat-sen University

Feasible and effective cell models for hepatitis B virus(HBV) infection are required for investigating the complete lifecycle of this virus, including the early steps of viral entry. Resistance to dimethyl sulfoxide/polyethylene glycol(DMSO/PEG), h NTCP expression, and a differentiated state are the limiting factors for successful HBV infection models. In the present study, we used a hepatoma cell line(Hu7^(hDNTCPh)) to overcome these limiting factors so that it exhibits excellent susceptibility to HBV infection. To achieve this goal, different hepatoma cell lines were tested with 2.5% DMSO/4%PEG8000, and one resistant cell line(Huh7 D) was used to construct a stable h NTCP-expressing cell line(Hu7^(hDNTCPh)) using a recombinant lentivirus system. Then, the morphological characteristics and differentiation molecular markers of Hu7^(hDNTCPh) cells with or without DMSO treatment were characterized. Finally, the susceptibility of Hu7^(hDNTCPh) cells to HBV infection was assessed. Our results showed that Huh7 D cells were resistant to 2.5% DMSO/4% PEG8000, whereas the others were not. Hu7^(hDNTCPh) cells were established to express a high level of h NTCP compared to liver extracts, and Hu7^(hDNTCPh) cells rapidly transformed into a non-dividing, well-differentiated polarized phenotype under DMSO treatment. Hu7^(hDNTCPh) cells fully supported the entire lifecycle of HBV infection. This cell culture system will be useful for the analysis of host-virus interactions, which should facilitate the discovery of antiviral drugs and vaccines.

关键词： Hepatitis B virus(HBV) Na+/taurocholate cotransporting polypeptide(NTCP) Huh7 dimethyl sulfoxide(DMSO) polyethylene glycol(PEG) susceptibility

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Repurposing of Antazoline Hydrochloride as an Inhibitor of Hepatitis B Virus DNA Secretion

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Virologica Sinica 2021年第3期36卷 501-509页

作者： Jing Li Yangyang Hu Yifei Yuan Yinan Zhao Qiqi Han Canyu Liu Xue Hu Yuan Zhou Yun Wang Yu Guo chunchen wu Xinwen Chen Rongjuan Pei College of Pharmacy Nankai UniversityTianjin 300350China State Key Lab of Virology Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China Shanghai Public Health Clinical Center Fudan UniversityShanghai 201508China Guangzhou Institutes of Biomedicine and Health Chinese Academy of SciencesGuangzhou 510530China Clinical Laboratory Maternal and Child Health Hospital of Hubei ProvinceWuhan 430070China

Hepatitis B virus(HBV) belongs to Hepadnaviridae family and mainly infects hepatocytes, which can cause acute or chronic hepatitis. Currently, two types of antiviral drugs are approved for chronic infection clinically: interferons and nucleos(t)ide analogues. However, the clinical cure for chronic infection is still rare, and it is a huge challenge for all researchers to develop high-efficiency, safe, non-tolerant, and low-toxicity anti-HBV drugs. Antazoline hydrochloride is a first-generation antihistamine with anticholinergic properties, and it is commonly used to relieve nasal congestion and in eye drops. Recently, an in vitro high-throughput evaluation system was constructed to screen nearly 800 compounds from the Food and Drug Administration(FDA)-approved Drug Library. We found that arbidol hydrochloride and antazoline hydrochloride can effectively reduce HBV DNA in the extracellular supernatant in a dose-dependent manner, with EC_(50) of4.321 lmol/L and 2.910 lmol/L in HepAD38 cells, respectively. Moreover, the antiviral effects and potential mechanism of action of antazoline hydrochloride were studied in different HBV replication systems. The results indicate that antazoline hydrochloride also has a significant inhibitory effect on HBV DNA in the extracellular supernatant of Huh7 cells,with an EC_(50) of 2.349 lmol/L. These findings provide new ideas for screening and research related to HBV agents.

关键词： Antazoline hydrochloride Hepatitis B virus(HBV) High-throughput evaluation system HepAD38

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Host HDAC4 regulates the antiviral response by inhibiting the phosphorylation of IRF3

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Journal of Molecular Cell Biology 2019年第2期11卷 158-169页

作者： Qi Yang Jielin Tang Rongjuan Pei XiaoXiao Gao Jing Guo Chonghui Xu Yun Wang QianWang chunchen wu Yuan Zhou Xue Hu He Zhao Yanyi Wang Xinwen Chen Jizheng Chen State Key Laboratory of Virology Wuhan Institute of Virology Chinese Academy of Sciences Wuhan 430071 China University of Chinese Academy of Sciences Beijing 100049 China Key Laboratory of Human Functional Genomics of Jiangsu Province School of Basic Medical Science Nanjing Medical University Nanjing 210093 China

Class II HDACs, such as HDAC4, are critical regulators of the immune response in various immune cells;however, its role in innate immunity remains largely ***, we report that the overexpression of HDAC4 suppresses the production of type I interferons triggered by pattern-recognition receptors (PRRs). HDAC4 repressed the translocation of transcription factor IRF3 to the nucleus, thereby decreasing IRF3-mediated IFN-β expression. In particular, we also determined that HDAC4 can be phosphorylated and simultaneously block the phosphorylation of IRF3 at Ser386 and Ser396 by TBK1 and IKKε, respectively, by interacting with the kinase domain of TBK1 and IKKε. Furthermore, IFN-β may stimulate the expression of HDAC4. Our findings suggest that HDAC4 acts as a regulator of PRR signaling and is a novel mechanism of negative feedback regulation for preventing an overreactive innate immune response.

关键词： HDAC4 antiviral response IRF3 TBK1 IKKε

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A Case of Hepatitis B Reactivation due to the Hepatitis B Virus Escape Mutant in a Patient undergoing Chemotherapy

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Virologica Sinica 2012年第6期27卷 369-372页

作者： chunchen wu Hui Shi Yun Wang Mengji LU Yang Xu Xinwen Chen State Key Lab of Virology Wuhan Institute of Virology Chinese Academy of Sciences Wuhan 430071 China Department of Microbiology Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China Institute of Virology University Hospital of Essen Essen D45122 Germany

A 62-year-old man had chronic hepatitis B virus （HBV） infection and was diagnosed with liver cirrhosis. At the time of diagnosis the patient＇s virologic markers were positive for hepatitis B surface antigen （HBsAg）, antibody to hepatitis B e antigen （anti-HBe） and antibody to hepatitis B core antigen （anti-HBc）, while antibody to hepatitis B surface antigen （anti-HBs） and HBV DNA were negative. Later the patient received chemotherapy for malignancy. However, this was interrupted due to elevated liver enzymes. At the same time HBV DNA became positive. Lamivudine （LMV） therapy was administered immediately. However, the levels of serum aminotransferase and total bilirubin （TB） were still rising. Finally the patient died of fulminant hepatic failure. A sequence revealed HBV genotype C （HBsAg subtype adw） with immune escape mutations, F8L, $34L, F41S, G44V, F93C, V96G, Lll0I, C149Y and F161Y. The high morbidity and mortality of this complication is one of the major obstacles to completing the standard treatment for malignancy in HBV carriers. Therefore, the relative risk of antiviral prophylactic failure should be further assessed and the optimal strategy for antiviral prophylaxis in HBsAg-positive patients with oncologic and hematologic malignancies undergoing chemotherapy should be revised.

关键词： Hepatitis B reactivation Escape mutant Lamivudine Malignancy

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