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Signal Transduction and Targeted Therapy 2022年第3期7卷 619-621页

作者： lunzhi yuan Huachen Zhu Kun Wu Ming Zhou Jian Ma Rirong Chen Qiyi Tang Tong Cheng Yi Guan Ningshao Xia State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics National Institute of Diagnostics and Vaccine Development in Infectious DiseasesSchool of Life SciencesSchool of Public HealthXiamen UniversityXiamenFujianChina State Key Laboratory of Emerging Infectious Diseases School of Public HealthLi Ko Shing Faculty of MedicineThe University of Hong KongHong KongSARChina Department of Microbiology Howard University College of MedicineWashingtonDCUSA

Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has infected more than 260 million people worldwide and causes coronavirus disease 2019(COVID-19)with clinical spectrum ranging from mild to severe pneumonia.Recent clinical trials and experimental animal studies demonstrated that the severity of COVID-19 is lower in the females than in males.

关键词： severity pneumonia clinical

Dexamethasone ameliorates severe pneumonia but slightly enhances viral replication in the lungs of SARS-CoV-2-infected Syrian hamsters

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Cellular & Molecular Immunology 2022年第2期19卷 290-292页

作者： lunzhi yuan Ming Zhou Jian Ma Xuan Liu Peiwen Chen Huachen Zhu Qiyi Tang Tong Cheng Yi Guan Ningshao Xia State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics National Institute of Diagnostics and Vaccine Development in Infectious DiseasesSchool of Life SciencesSchool of Public HealthXiamen UniversityXiamenFujianChina. State Key Laboratory of Emerging Infectious Diseases School of Public HealthLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongSARChina. Guangdong-Hong Kong Joint Laboratory of Emerging Infectious Diseases/Joint Laboratory for International Collaboration in Virology and Emerging Infectious Diseases Joint Institute of Virology(STU/HKU)Shantou UniversityShantouGuangdongChina. EKIH Pathogen Research Institute Futian DistrictShenzhenGuangdongChina. Department of Microbiology Howard University College of MedicineWashingtonDCUSA. Research Unit of Frontier Technology of Structural Vaccinology Chinese Academy of Medical SciencesXiamenFujianChina.

The pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in more than 230 million cases and over four million deaths worldwide.Furthermore,multiple emerging SARS-CoV-2 variants have shown enhanced infectivity,transmissibility,pathogenicity and ability to escape neutralization by vaccine-induced humoral immunity[1].The antibody resistance of SARS-CoV-2 variants constitutes a challenge for current vaccines and therapeutic antibodies.No specific antiviral is currently available for coronavirus in humans[2].Although remdesivir was approved by the FDA for the treatment of SARS-CoV-2 infection,the therapeutic effect is limited,particularly for critical cases with severe pneumonia.

关键词： immunity pneumonia vaccine

Infection,pathology and interferon treatment of the SARS-CoV-2 Omicron BA.1 variant in juvenile,adult and aged Syrian hamsters

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Cellular & Molecular Immunology 2022年第12期19卷 1392-1399页

作者： lunzhi yuan Huachen Zhu Peiwen Chen Ming Zhou Jian Ma Xuan Liu Kun Wu Rirong Chen Qiwei Liu Huan Yu Lifeng Li Jia Wang Yali Zhang Shengxiang Ge Quan yuan Qiyi Tang Tong Cheng Yi Guan Ningshao Xia State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics National Institute of Diagnostics and Vaccine Development in Infectious DiseasesSchool of Life SciencesSchool of Public HealthXiamen UniversityXiamenFujianChina State Key Laboratory of Emerging Infectious Diseases School of Public HealthLi Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina Guangdong-Hong Kong Joint Laboratory of Emerging Infectious Diseases/Joint Laboratory for International Collaboration in Virology and Emerging Infectious Diseases Joint Institute of Virology(STU/HKU)Shantou UniversityShantouGuangdongChina EKIH Pathogen Research Institute Futian DistrictShenzhenGuangdongChina Department of Microbiology Howard University College of MedicineWashingtonDCUSA

The new predominant circulating SARS-CoV-2 variant,Omicron,can robustly escape current vaccines and neutralizing antibodies.Although Omicron has been reported to have milder replication and disease manifestations than some earlier variants,its pathogenicity in different age groups has not been well elucidated.Here,we report that the SARS-CoV-2 Omicron BA.1 sublineage causes elevated infection and lung pathogenesis in juvenile and aged hamsters,with more body weight loss,respiratory tract viral burden,and lung injury in these hamsters than in adult hamsters.Juvenile hamsters show a reduced interferon response against Omicron BA.1 infection,whereas aged hamsters show excessive proinflammatory cytokine expression,delayed viral clearance,and aggravated lung injury.Early inhaled IFN-α2b treatment suppresses Omicron BA.1 infection and lung pathogenesis in juvenile and adult hamsters.Overall,the data suggest that the diverse patterns of the innate immune response affect the disease outcomes of Omicron BA.1 infection in different age groups.

关键词： SARS-CoV-2 Omicron Lung pathology Innate immune response Interferon treatment

Persisting lung pathogenesis and minimum residual virus in hamster after acute COVID-19

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Protein & Cell 2022年第1期13卷 72-77页

作者： lunzhi yuan Huachen Zhu Ming Zhou Jian Ma Rirong Chen Liuqin Yu Wenjia Chen Wenshan Hong Jia Wang Yao Chen Kun Wu Wangheng Hou Yali Zhang Shengxiang Ge Yixin Chen Quan yuan Qiyi Tang Tong Cheng Yi Guan Ningshao Xia State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics National Institute of Diagnostics and Vaccine Development in Infectious DiseasesSchool of Life SciencesSchool of Public HealthXiamen UniversityXiamen 361000China State Key Laboratory of Emerging Infectious Diseases The University of Hong KongHong KongChina Joint Institute of Virology(Shantou University and The University of Hong Kong) Guangdong-Hongkong Joint Laboratory of Emerging Infectious DiseasesShantou UniversityShantou 515063China Department of Microbiology Howard University College of MedicineWashingtonDC 20059USA Research Unit of Frontier Technology of Structural Vaccinology Chinese Academy of Medical SciencesXiamen 361102China

Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has infected more than 200 million people,causing coronavirus disease 2019(COVID-19)worldwide.Lungs are the primary target organ of SARS-CoV-2 infection.The mild COVID-19 cases develop symptoms of fever,fatigue,muscle weakness,chest pain,headache and cough(Chen et al.,2020;Wang et al.,2020;Zhu et al.,2020),while severe COIVD-19 cases might have pneumonia,breathing difficulties,multiple organ failure and death(Chen et al.,2020;Wang et al.,2020;Zhu et al.,2020).Both the clinicians and researchers have largely focused on the acute phase of COVID-19,but the long-term health consequences of the COVID-19 patients after clinical recovery remain less investigated.Several clinical cohorts demonstrated that some patients discharged from hospital still experience symptoms including fatigue,muscle weakness,chest pain,cough and breathing difficulties(Carfi et al.,2020;Lim et al.,2020;Huang et al.,2021).Moreover,severely impaired pulmonary diffusion capacities and abnormal chest imaging manifestations were observed in some convalescent patients(Huang et al.,2021).Surprisingly,residual virus(An et al.,2020;Yao et al.,2020;Kim et al.,2021)were detected in some convalescent patients.

关键词： acute impaired pathogenesis

Liver chimeric mice with tupaia hepatocyte transplantation as an animal model for hepatitis B virus infection and antiviral therapy

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Biosafety and Health 2019年第2期1卷 76-83页

作者： lunzhi yuan Yao Chen Xuan Liu Yali Zhang Ming Zhou Kun Wu Quan yuan Tong Cheng Ningshao Xia State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics School of Public HealthXiamen UniversityXiamen 361102China National Institute of Diagnostics and Vaccine Development in Infectious Diseases School of Life SciencesXiamen UniversityXiamen 361102China

The human liver chimeric mouse is a milestone animal model for hepatitis B virus(HBV)infection.Such mice with primary human hepatocyte(PHH)transplantation are adequate to support chronic HBV infection for several weeks and to evaluate antiviral drugs.However,the drawbacks of PHHs include lack of available donors,poor expansion in vitro and ethical issues that limit the application of human liver chimeric mice,necessitating the search for alternatives.Here,we transplanted primary tupaia hepatocytes(PTHs)into the livers of immunodeficient mice and achieved high liver chimerism within six weeks.These tupaia liver chimeric mice are adequate to support chronic infection of the four common HBV genotypes A,B,C and D for 36 weeks,as well as evaluate of antiviral drugs,including hepatitis B immune globulin(HBIG),monoclonal antibody and nucleoside analogues(NAs),for preventative therapy and treatment post infection.In conclusion,the tupaia liver chimeric mouse model provides a convenient,efficient and stable animal model for chronic HBV infection and long-term drug evaluation.

关键词： Tupaia Hepatitis B Liver chimeric mice Infectious animal model Antiviral therapy

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Gender associates with both susceptibility to infection and pathogenesis of SARS-CoV-2 in Syrian hamster

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Signal Transduction and Targeted Therapy 2021年第4期6卷 1369-1376页

作者： lunzhi yuan Huachen Zhu Ming Zhou Jian Ma Rirong Chen Yao Chen Liqiang Chen Kun Wu Minping Cai Junping Hong Lifeng Li Che Liu Huan Yu Yali Zhang Jia Wang Tianying Zhang Shengxiang Ge Jun Zhang Quan yuan Yixin Chen Qiyi Tang Honglin Chen Tong Cheng Yi Guan Ningshao Xia State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics National Institute of Diagnostics and Vaccine Development in Infectious DiseasesSchool of Life SciencesSchool of Public HealthXiamen UniversityXiamenP.R.China State Key Laboratory of Emerging Infectious Diseases The University of Hong KongHong KongP.R.China Joint Institute of Virology(Shantou University and The University of Hong Kong) Guangdong-Hongkong Joint Laboratory of Emerging Infectious DiseasesShantou UniversityShantouP.R.China Department of Microbiology Howard University College of MedicineWashingtonDCUSA Research Unit of Frontier Technology of Structural Vaccinology Chinese Academy of Medical SciencesXiamenFujianChina

Epidemiological studies of the COVID-19 patients have suggested the male bias in outcomes of lung illness.To experimentally demonstrate the epidemiological results,we performed animal studies to infect male and female Syrian hamsters with SARS-CoV-2.Remarkably,high viral titer in nasal washings was detectable in male hamsters who presented symptoms of weight loss,weakness,piloerection,hunched back and abdominal respiration,as well as severe pneumonia,pulmonary edema,consolidation,and fibrosis.In contrast with the males,the female hamsters showed much lower shedding viral titers,moderate symptoms,and relatively mild lung pathogenesis.The obvious differences in the susceptibility to SARS-CoV-2 and severity of lung pathogenesis between male and female hamsters provided experimental evidence that SARS-CoV-2 infection and the severity of COVID-19 are associated with gender.

关键词： pathogenesis lung infection

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面向新冠肺炎疫情防控需求的应用基础研究

中国科学基金 2022年第4期36卷 615-623页

作者：袁伦志张天英张军夏宁邵厦门大学分子疫苗学和分子诊断学国家重点实验室厦门大学国家传染病诊断试剂与疫苗工程技术研究中心

严重急性呼吸综合征冠状病毒2(Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV-2)全球大流行导致的新冠肺炎疫情仍在持续，不断进化的变异毒株谱系具有较强的免疫逃逸和突破性感染能力，一系列新冠肺炎后遗症陆续被发现，... 详细信息

严重急性呼吸综合征冠状病毒2(Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV-2)全球大流行导致的新冠肺炎疫情仍在持续，不断进化的变异毒株谱系具有较强的免疫逃逸和突破性感染能力，一系列新冠肺炎后遗症陆续被发现，并可能在未来对人类社会造成严重的医疗负担。我国面临“外防输入、内防反弹”的巨大抗疫压力，不仅需要全面统筹疫情防控和经济社会发展，还需要积极为将来全面放开出入境限制做好科技储备。建立完备的疫情防控体系和群体免疫屏障，研究和发展抗疫产品和科学技术，进一步减少重症和死亡，是保障人民生命健康、打赢抗疫“拉锯战”的法宝。厦门大学国家传染病诊断试剂与疫苗工程技术研究中心团队长期以来在国家自然科学基金项目的支持下，形成了坚实的感染性疾病研究积累，建立了系统的生物医药研究平台，锻造了一支朝气蓬勃的科研创新团队；面对复杂的疫情发展态势，围绕“诊断、预防、治疗”三方面的防控产品需求，在SARS-CoV-2检测技术体系、鼻喷流感病毒载体新冠疫苗和重组蛋白新冠疫苗、广谱中和抗体与小分子药物筛选、重症肺炎动物模型和致病机制等方面取得了一系列研究进展，为我国疫情防控和公共卫生事业提供了重要的科技支撑。

关键词：新冠病毒新冠肺炎诊断创新疫苗治疗性抗体动物模型高通量药物筛选

Histones released by NETosis enhance the infectivity of SARS-CoV-2 by bridging the spike protein subunit 2 and sialic acid on host cells

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Cellular & Molecular Immunology 2022年第5期19卷 577-587页

作者： Weiqi Hong Jingyun Yang Jun Zou Zhenfei Bi Cai He Hong Lei Xuemei He Xue Li Aqu Alu Wenyan Ren Zeng Wang Xiaohua Jiang Kunhong Zhong Guowen Jia Yun Yang Wenhai Yu Qing Huang Mengli Yang Yanan Zhou yuan Zhao Dexuan Kuang Junbin Wang Haixuan Wang Siyuan Chen Min Luo Ziqi Zhang Tiangi Lu Li Chen Haiying Que Zhiyao He Qiu Sun Wei Wang Guobo Shen Guangwen Lu Zhiwei Zhao Li Yang Jinliang Yang Zhenling Wang Jiong Li Xiangrong Song lunzhi Dai Chong Chen Jia Geng Maling Gou Lu Chen Haohao Dong Yong Peng Canhua Huang Zhiyong Qian Wei Cheng Changfa Fan Yuquan Wei Zhaoming Su Aiping Tong Shuaiyao Lu Xiaozhong Peng Xiawei Wei Laboratory of Aging Research and Cancer Drug Targeting State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityNo.17Block 3Southern Renmin RoadChengduSichuan610041China National Kunming High-level Biosafety Primate Research Center Institute of Medical BiologyChinese Academy of Medical Sciences and Peking Union Medical CollegeYunnanChina Westvac Biopharm Co. Ltd.No.618Fenghuang RoadShuangliu DistrictChengduSichuanChina Division of Animal Model Research Institute for Laboratory Animal ResourcesNational Institutes for Food and Drug Control102629BeijingChina State Key Laboratory of Medical Molecular Biology Department of Molecular Biology and BiochemistryInstitute of Basic Medical SciencesMedical Primate Research CenterNeuroscience CenterChinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijingChina

Neutrophil extracellular traps(NETs)can capture and kill viruses,such as influenza viruses,human immunodeficiency virus(HIV),and respiratory syncytial virus(RSV),thus contributing to host defense.Contrary to our expectation,we show here that the histones released by NETosis enhance the infectivity of SARS-CoV-2,as found by using live SARS-CoV-2 and two pseudovirus systems as well as a mouse model.The histone H3 or H4 selectively binds to subunit 2 of the spike(S)protein,as shown by a biochemical binding assay,surface plasmon resonance and binding energy calculation as well as the construction of a mutant S protein by replacing four acidic amino acids.Sialic acid on the host cell surface is the key molecule to which histones bridge subunit 2 of the S protein.Moreover,histones enhance cell-cell fusion.Finally,treatment with an inhibitor of NETosis,histone H3 or H4,or sialic acid notably affected the levels of sgRNA copies and the number of apoptotic cells in a mouse model.These findings suggest that SARS-CoV-2 could hijack histones from neutrophil NETosis to promote its host cell attachment and entry process and may be important in exploring pathogenesis and possible strategies to develop new effective therapies for COVID-19.

关键词： COVID-19 SARS-CoV-2 neutrophil extracellular traps histones sialic acid

针刺联合中西药治疗糖尿病视网膜病变的疗效观察

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上海针灸杂志 2022年第11期41卷 1065-1070页

作者：冯媛陈艳玲刘伦志恩施土家族苗族自治州中心医院恩施445000 湖北民族学院附属民大医院恩施445000

目的观察针刺联合中西药治疗糖尿病视网膜病变(DR)的临床疗效。方法将123例(123眼)气阴两虚型DR患者(单纯型)分为中药组、针刺组和联合组,每组41例(41眼)。中药组患者给予夜视复明汤联合常规西药治疗,针刺组患者给予针刺疗法联合常规西... 详细信息

目的观察针刺联合中西药治疗糖尿病视网膜病变(DR)的临床疗效。方法将123例(123眼)气阴两虚型DR患者(单纯型)分为中药组、针刺组和联合组,每组41例(41眼)。中药组患者给予夜视复明汤联合常规西药治疗,针刺组患者给予针刺疗法联合常规西药治疗,联合组患者给予针刺疗法联合夜视复明汤及常规西药治疗。比较3组患者临床疗效,观察3组治疗前后眼底检查情况(视网膜循环时间、黄斑水肿程度及微血管病变程度)和血清钙镁离子、可溶性细胞黏附分子(sICAM-1)、结缔组织生长因子(CTGF)水平及视网膜眼底动脉血流动力学[收缩期最大流速(PSV)和舒张末期血流速度(EDV)]变化情况,观察随访1年后3组患者病情进展情况。结果联合组总有效率(97.6%)明显高于中药组(85.4%)及针刺组(82.9%)(P<0.05)。治疗后,3组视网膜循环时间较治疗前减少,黄斑水肿程度及微血管病变程度较治疗前降低,且联合组优于中药组及针刺组,差异有统计学意义(P<0.05);3组血清sICAM-1和CTGF水平均低于治疗前,血清钙镁离子均高于治疗前,且联合组优于中药组及针刺组(P<0.05);3组眼底动脉PSV和EDV水平均高于治疗前,且联合组高于中药组及针刺组(P<0.05)。随访1年后,联合组患者病情进展率(4.9%)明显低于针刺组(22.0%)及中药组(19.5%)(P<0.05)。结论针刺联合中西药治疗DR患者疗效显著,能有效改善患者临床症状及眼底动脉血流动力学水平,延缓视网膜病变病情进展。

关键词：针刺疗法针药并用糖尿病视网膜疾病糖尿病并发症血流动力学

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一种可快速、持久且广谱保护新冠病毒感染的鼻喷减毒流感病毒载体新冠病毒疫苗

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Science Bulletin 2022年第13期67卷 1372-1387,M0004页

作者：陈俊煜王培袁伦志张良张丽敏赵慧陈聪洁王熹婧韩金乐陈耀德贾继宗卢珍洪俊平陆梓涔王倩陈日荣戚若垚马建周明于欢庄春兰刘晓辉韩强远王国松苏迎盈袁权程通吴婷叶祥忠张天英李长贵张军朱华晨陈毅歆陈鸿霖夏宁邵 State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics National Institute of Diagnostics and Vaccine Development in Infectious DiseasesSchool of Life SciencesSchool of Public HealthXiamen UniversityXiamen 361102China State Key Laboratory of Emerging Infectious Diseases School of Public HealthLi Ka Shing Faculty of MedicineThe University of Hong KongHong Kong 999077China National Institute for Food and Drug Control Beijing 102629China Beijing Wantai Biological Pharmacy Enterprise Co. Ltd.Beijing 102206China Guangdong-Hong Kong Joint Laboratory of Emerging Infectious Diseases/Joint Laboratory for International Collaboration in Virology and Emerging Infectious Diseases Joint Institute of Virology(STU/HKU)Shantou UniversityShantou 515063China EKIH Pathogen Research Institute Shenzhen 518067China

肌注式新冠病毒疫苗在呼吸道局部诱导的免疫应答较有限,不能高效阻止新冠病毒入侵呼吸道细胞.为此,该研究利用双重减毒的流感病毒载体(CA4-d NS1)开发出一种携带新冠病毒RBD基因的可经鼻腔喷雾方式接种的新冠病毒疫苗CA4-dNS1-nCoV-RBD... 详细信息

肌注式新冠病毒疫苗在呼吸道局部诱导的免疫应答较有限,不能高效阻止新冠病毒入侵呼吸道细胞.为此,该研究利用双重减毒的流感病毒载体(CA4-d NS1)开发出一种携带新冠病毒RBD基因的可经鼻腔喷雾方式接种的新冠病毒疫苗CA4-dNS1-nCoV-RBD(简称dNS1-RBD).该疫苗在重症新冠肺炎仓鼠模型中表现出良好的保护效果,鼻喷接种1天后即可快速起效,两剂次鼻喷接种后可提供9个月以上的长效保护,表现为疫苗组仓鼠的体重未见明显下降,肺组织病理无明显损伤.该疫苗对Omicron等各种新冠病毒关切突变株均有广谱作用.另外,小鼠实验显示该疫苗还可广谱保护H1N1和H5N1流感病毒感染.该疫苗的保护机制涉及呼吸道局部的先天免疫应答、特异性T细胞应答、粘膜Ig A抗体应答和体液Ig G抗体应答等.总之,该研究表明快速、持久且广谱的鼻喷流感载体新冠病毒疫苗可与现有肌注式新冠病毒疫苗形成互补,共同抗击新冠疫情.

关键词：病毒疫苗流感病毒减毒病毒感染免疫应答 H1N1 明显损伤病毒入侵

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