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Cholinergic α7 nAChR signaling suppresses SARS-CoV-2 infection and inflammation in lung epithelial cells

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Journal of Molecular Cell Biology 2023年第7期15卷 73-76页

作者： Jing Wen Jing Sun Yanhong Tang Jincun Zhao Xiao Su Unit of Respiratory Infection and Immunity Institut Pasteur of ShanghaiChinese Academy of SciencesShanghai 200031China CAS Key Laboratory of Molecular Virology and Immunology Institut Pasteur of ShanghaiChinese Academy of SciencesShanghai 200031China University of Chinese Academy of Sciences Beĳing 100049China State Key Laboratory of Respiratory Disease National Clinical Research Centre for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China

DearEditor,Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,has led to>6 million deaths and posed a huge threat to the global economy and public health.SARS-CoV-2 enters lungepithelial cellsdependingon the binding between SARS-CoV-2 S protein and the host receptor angiotensinconverting enzyme 2(ACE2).

关键词： ACE2 lung infection

Three-dimensional path following control system for net cage inspection using bionic robotic fish

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Information Processing in Agriculture 2022年第1期9卷 100-111页

作者： Yuanrong Chen Jingfen Qiao jincun Liu Ran zhao Dong An Yaoguang Wei College of Information and Electrical Engineering China Agricultural UniversityBeijing 100083China National Innovation Centre for Digital Fishery China Agricultural UniversityBeijing 100083China Beijing Engineering and Technology Research Centre for Internet of Things in Agriculture Beijing 100083China Key Laboratory of Agricultural Information Acquisition Technology Ministry of AgricultureBeijing 100083China School of Computing The Australian National UniversityCanberra2601Australia

With the increasing impacts of overfishing and environmental pollution,the deep-sea cage culture of marine fishes has become an important direction of mariculture.In this paper,a tuna-like robotic fish with a three-dimensional helix path-following control system is designed for deep-sea net cage inspection.To mimic the flexibility of the fish’s movement,the kinematic model of the robotic fish adopts a tuna-like double-joint design with an addi-tional thruster device at the tail.Since the descending interval control plays a critical role in deep-sea net cage inspection,the control system utilizes the proportion integration differ-entiation(PID)based fuzzy logic control method to control the descending interval and yaw angle during the helix path movement.A polar coordinate path definition method is also proposed to simplify the reference path definition during net cage inspection.The experi-mental results demonstrates that the proposed three-dimensional path-following model can conduct net inspection task in an interferential environment and move along prede-fined reference path.

关键词： Net cage inspection Bionic robotic fish Path following Three-dimensional motion control

A pair of SARS-CoV-2 nucleocapsid protein monoclonal antibodies shows high specificity and sensitivity for diagnosis

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Virologica Sinica 2022年第6期37卷 942-945页

作者： An-Kai Zhu Sa-Sa Li Shu-Pei Yu zhao-Yong Zhang Huan Li Jing-Feng Li Shan-Shan Gao Heng Chen Jincun Zhao Run Shi Mingjian Lu Chaoyang Li Affiliated Cancer Hospital and Institute of Guangzhou Medical University State Key Laboratory of Respiratory DiseaseKey Laboratory for Cell Homeostasis and Cancer Research of Guangdong High Education InstituteGuangzhou510095China State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou510182China Department of Interventional Radiology Affiliated Cancer Hospital and Institute of Guangzhou Medical UniversityGuangzhou510095China

Dear Editor,Severe Acute Respiratory Syndrome Coronavirus Type 2(SARS-CoV-2) is the pathogen of the coronavirus disease 2019(COVID-19), which has spread worldwide.SARS-CoV-2 is an enveloped virus belongs to the family of β-coronavirus(Xu et al., 2020). Its genome is a linear single-stranded positive-sense RNA about 30,000 nucleotides packed inside a virion with a diameter of 100 nm and a volume of about 10^(6)nm^(3)(Bar-On et al., 2020).

关键词： al. diagnosis specificity

SARS-CoV-2 immunity in animal models

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Cellular & Molecular Immunology 2024年第2期21卷 119-133页

作者： zhao Chen Yaochang Yuan Qingtao Hu Airu Zhu Fenghua Chen Shu Li Xin Guan Chao Lv Tian Tang Yiyun He Jinling Cheng Jie Zheng Xiaoyu Hu Jingxian zhao Jincun Zhao Jing Sun State Key Laboratory of Respiratory Disease National Clinical Research Centre for Respiratory DiseaseNational Centre for Respiratory MedicineGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510182China GMU-GIBH Joint School of Life Sciences Guangzhou Medical UniversityGuangzhou 510000China Guangzhou National Laboratory GuangzhouGuangdong 510005China Shanghai Institute for Advanced Immunochemical Studies School of Life Science and TechnologyShanghaiTech UniversityShanghai 201210China Institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People’s Hospitalthe Second Affiliated HospitalSchool of MedicineSouthern University of Science and TechnologyShenzhen 518005China

The COVID-19 pandemic,which was caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has become a worldwide health crisis due to its transmissibility.SARS-CoV-2 infection results in severe respiratory illness and can lead to significant complications in affected individuals.These complications encompass symptoms such as coughing,respiratory distress,fever,infectious shock,acute respiratory distress syndrome(ARDS),and even multiple-organ failure.Animal models serve as crucial tools for investigating pathogenic mechanisms,immune responses,immune escape mechanisms,antiviral drug development,and vaccines against SARS-CoV-2.Currently,various animal models for SARS-CoV-2 infection,such as nonhuman primates(NHPs),ferrets,hamsters,and many different mouse models,have been developed.Each model possesses distinctive features and applications.In this review,we elucidate the immune response elicited by SARS-CoV-2 infection in patients and provide an overview of the characteristics of various animal models mainly used for SARS-CoV-2 infection,as well as the corresponding immune responses and applications of these models.A comparative analysis of transcriptomic alterations in the lungs from different animal models revealed that the K18-hACE2 and mouse-adapted virus mouse models exhibited the highest similarity with the deceased COVID-19 patients.Finally,we highlighted the current gaps in related research between animal model studies and clinical investigations,underscoring lingering scientific questions that demand further clarification.

关键词： COVID-19 SARS-CoV-2 animal models immune response

RNA-induced liquid phase separation of SARS-CoV-2 nucleocapsid protein facilitates NF-kB hyper-activation and inflammation

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Signal Transduction and Targeted Therapy 2021年第5期6卷 1601-1613页

作者： Yaoxing Wu Ling Ma Sihui Cai Zhen Zhuang Zhiyao zhaou Shouheng Jin Weihong Xie Lingli Zhou Lei Zhang Jincun Zhao Jun Cui MOE Key Laboratory of Gene Funrtion and Regulation State Key Laboratory of BiocontrolSchool of Life SciencesSun Yat-sen UniversityGuangzhouGuangdongChina State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory DiseaseThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina

The ongoing 2019 novel coronavirus disease(COVID-19)caused by SARS-CoV-2 has posed a worldwide pandemic and a major global public health threat.The severity and mortality of COVID-19 are associated with virus-induced dysfunctional inflammatory responses and cytokine storms.However,the interplay between host inflammatory responses and SARS-CoV-2 infection remains largely unknown.Here,we demonstrate that SARS-CoV-2 nucleocapsid(N)protein,the major structural protein of the virion,promotes the virus-triggered activation of NF-kB signaling.After binding to viral RNA,N protein robustly undergoes liquid-liquid phase separation(LLPS),which recruits TAK1 and IKK complex,the key kinases of NF-kB signaling,to enhance NF-kB activation.Moreover,1,6-hexanediol,the inhibitor of LLPS,can attenuate the phase separation of N protein and restrict its regulatory functions in NF-kB activation.These results suggest that LLPS of N protein provides a platform to Induce NF-kB hyper-activation,which could be a potential therapeutic target against COVID-19 severe pneumonia.

关键词： inflammation separation activation

Immune responses to SARS-CoV-2 infection in Humans and ACE2 humanized mice

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Fundamental Research 2021年第2期1卷 124-130页

作者： Airu Zhu zhao Chen Yanqun Wang Qiuhui Zeng Jing Sun Zhen Zhuang Fang Li Jingxian zhao Jincun Zhao Nanshan Zhong State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510120China

The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)represents a major public health threat worldwide.Insight into protective and pathogenic aspects of SARS-CoV-2 immune responses is critical to work out effective therapeutics and develop vaccines for controlling the disease.Here,we review the present literature describing the innate and adaptive immune responses including innate immune cells,cytokine responses,antibody responses and T cell responses against SARS-CoV-2 in human infection,as well as in AEC2-humanized mouse infection.We also summarize the now known and unknown about the role of the SARS-CoV-2 immune responses.By better understanding the mechanisms that drive the immune responses,we can tailor treatment strategies at specific disease stages and improve our response to this worldwide public health threat.

关键词： SARS-CoV-2 Innate immune response Humoral immune responses T cell response Mouse model

Main protease of SARS-CoV-2 serves as a bifunctional molecule in restricting type I interferon antiviral signaling

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Signal Transduction and Targeted Therapy 2020年第1期5卷 646-648页

作者： Yaoxing Wu Ling Ma Zhen Zhuang Sihui Cai Zhiyao zhao Lingli Zhou Jing Zhang Pei-Hui Wang Jincun Zhao Jun Cui MOE Key Laboratory of Gene Function and Regulation State Key Laboratory of BiocontrolSchool of Life SciencesSun Yat-sen University510275 GuangzhouGuangdongChina State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory DiseaseThe First Affiliated Hospital of Guangzhou Medical University510182 GuangzhouGuangdongChina Advanced Medical Research Institute Cheeloo College of MedicineShandong University250012 JinanShandongChina

Dear Editor,At present,the world is suffering from an ongoing pandemic of 2019 novel coronavirus(COVID-19)which is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2/2019-nCoV).To date,>20 million cases were confirmed with a death toll at>700,000.Although there are no clinically specific and effective antiviral treatments toward SARS-CoV-2 infection so far,the pathological study of SARS-CoV-2 infection and the development of SARS-CoV-2-specific vaccines are progressing rapidly within these several months.1 However,few reports mentioned the mechanism employed by SARS-CoV-2 for evading from surveillance of immune system.

关键词： acute respiratory death

A novel luciferase immunosorbent assay performs better than a commercial enzyme-linked immunosorbent assay to detect MERS-CoV specific IgG in humans and animals

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Biosafety and Health 2019年第3期1卷 134-143页

作者： Wenling Wang Tianyu Wang Yao Deng Peihua Niu Ruhan A Jincun Zhao Malik Peiris Shixing Tang Wenjie Tan MHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChina CDCBeijing 102206China Guangdong Provincial Key Laboratory of Tropical Disease Research Department of EpidemiologySchool of Public HealthSouthern Medical UniversityGuangzhou 510515China State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory DiseaseThe first Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510182China School of Public Health Li Ka Shing Faculty of MedicineThe University of Hong KongPokfulamHong Kong Special Administrative Region Center for Biosafety Mega-science Chinese Academy of SciencesBeijing 100101China

The Middle East respiratory syndrome(MERS)is a lethal zoonosis caused by MERS coronavirus(MERS-CoV)and poses a significant threat to public health worldwide.Therefore,a rapid,sensitive,and specific serologic test for detecting anti-MERS-CoV antibodies in both humans and animals is urgently needed for the successful management of this illness.Here,we evaluated various novel luciferase immunosorbent assays(LISA)based on nucleocapsid protein(NP)as well as fragments derived from spike protein(S)including subunit 1(S1),N terminal domain(NTD),receptorbinding domain(RBD)and subunit 2(S2)of S for the detection of MERS-CoV-specific IgG.Fusion proteins,including nanoluciferase(NLuc)and various fragments derived from the NP or S protein of MERS-CoV,were expressed in human embryonic kidney 293 T cells.LISAs that detected anti-MERS-CoV IgG were further developed using cell lysates expressing various fusion proteins.Panels of human or animal samples infected with MERS-CoV were used to analyze the sensitivity and specificity of various LISAs in reference to a MERS-CoV RT-PCR,commercial S1-based ELISA,and pseudovirus particle neutralization test(ppNT).Our results showed that the S1-,RBD-,and NP-LISAs were more sensitive than the NTD-and S2-LISAs for the detection of anti-MERS-CoV IgG.Furthermore,the S1-,RBD-,and NP-LISAs were more sensitive(by at least 16-fold)than the commercially available S1-ELISA.Moreover,the S1-,RBD-,and NPLISA specifically recognized anti-MERS-CoV IgG and did not cross-react with samples derived from other human CoV(OC43,229E,HKU1,NL63)-infected patients.More importantly,these LISAs proved their applicability and reliability for detecting anti-MERS-CoV IgG in samples from camels,monkeys,and mice,among which the RBD-LISA exhibited excellent performance.The results of this study suggest that the novel MERS-CoV RBD-and S1-LISAs are highly effective platforms for the rapid and sensitive detection of anti-MERS-CoV IgG in human and animal samples.These assays have the potential to be used as serologic tests for

关键词： Luciferase immunosorbent assay(LISA) MERS-CoV Serological IgG detection Samples of humans and animals

Genetic and pathogenicity diversity of dengue virus type 2 strains circulating in Guangdong,China

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Biosafety and Health 2021年第6期3卷 333-342页

作者： Lu Zhang Lingzhai zhao zhaoyong Zhang Wenxin Hong Jian Wang Shuang Qiu Huiqin Yang Mian Gan Jing Sun Jingxian zhao Yanqun Wang Jincun Zhao Fuchun Zhang Institute of Infectious Disease Guangzhou Eighth People's Hospital of Guangzhou Medical UniversityGuangzhou 510120China Technology Center Guangzhou CustomsGuangzhou 510120China State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China

Dengue fever is a mosquito-borne viral disease spread in tropical and subtropical regions caused by the dengue virus(DENV).DENV causes a febrile illness,severe forms including hemorrhagic fevers and shock with fatalities in humans.DENV-2 is frequently associated with severe dengue infections and epidemics.DENV-2 strains from Guangdong,China,have not been characterized to compare the phylogenetics and pathogenicity of different DENV-2 subgenotype strains in both vitro and vivo.A total of 22 patients tested to be DENV-2 positive and were enrolled in this study,22 complete genomes were obtained by virus isolation and high-throughput sequencing.Phylogenetic and single amino polymorphism(SAP)analysis indicated that two major subgenotypes(A and C)of DENV-2 Cosmopolitan were prevalent in Guangdong in 2018.The apparent change of major subgenotypes of DENV-2 circulating in Guangdong indicated the diversity of DENV-2 strains,including endemic genotype and imported genotype.It alerted the risk of cross-border transmission of DENV.A significant difference in replication rate was observed in C6/36 between different DENV-2 strains,although growth kinetics comparison of different DENV-2 Cosmopolitan subgenotypes showed similar profiles.DENV-2 subgenotypes(A and C)replicated efficiently in IFNAR−/−C57BL/6 mice,and subgenotype A of Cosmopolitan infected mice showed increased weight loss and delayed viral clearance compared with the subgenotype C group.DENV-2 prevalent in Guangdong in 2018 showed apparent genetic and pathogenicity diversity in both vitro and vivo,indicating the necessity of molecular surveillance and exploration of the relationship between its pathogenicity and clinical characteristics.

关键词： DENV-2 Genetic Pathogenicity Diversity