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Identification of residues in Lassa virus glycoprotein 1 involved in receptor switch

Virologica Sinica 2024年第4期39卷 600-608页

作者： Jiao Guo Yi Wan Yang Liu Xiaoying Jia Siqi Dong Gengfu Xiao Wei Wang State Key Laboratory of Virology Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430071China university of the Chinese Academy of Sciences Beijing 100049China The Xi'an Key Laboratory of Pathogenic Microorganism and Tumor immunity School of Basic MedicineXi'an Medical UniversityXi'an 710021China

Lassa virus(LASV)is an enveloped,negative-sense RNA virus that causes Lassa hemorrhagic *** entry of LASV requires the viral glycoprotein 1(GP1)to undergo a receptor switch from its primary receptor alpha-dystroglycan(α-DG)to its endosomal receptor lysosome-associated membrane protein 1(LAMP1).A conserved histidine triad in LASV GP1 has been reported to be responsible for receptor *** test the hypothesis that other non-conserved residues also contribute to receptor switch,we constructed a series of mutant LASV GP1 proteins and tested them for binding to *** residues,L84,K88,L107,and H170,were identified as critical for receptor *** any of the four residues with the corresponding lymphocytic choriomeningitis virus(LCMV)residue(L84 N,K88E,L10F,and H170S)reduced the binding affinity of LASV GP1 for ***,all mutations caused decreases in glycoprotein precursor(GPC)-mediated membrane fusion at both pH 4.5 and *** infectivity of pseudotyped viruses bearing either GPCL84N or GPCK88E decreased sharply in multiple cell types,while L107F and H170S had only mild effects on *** biolayer light interferometry assay,we found that all four mutants had decreased binding affinity to LAMP1,in the order of binding affinity being L84 N>L107F>K88E>*** four amino acid loci identified for the first time in this study have important reference significance for the in-depth investigation of the mechanism of receptor switching and immune escape of LASV occurrence and the development of reserve anti-LASV infection drugs.

关键词： Lassa virus(LASV) Lysosome-associated membrane protein 1 (LAMP1) Glycoprotein Receptor switch Membrane fusion

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Coming of age:the formation and function of age-associated B cells

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Cellular & Molecular Immunology 2024年第4期21卷 311-312页

作者： Ke Rui Nan Che Kongyang Ma Hejian Zou Fan Xiao Liwei Lu Department of Laboratory Medicine Institute of Medical Immunology of Jiangsu UniversityAffiliated Hospital of Jiangsu UniversityZhenjiangChina Department of Rheumatology and Immunology Nanjing First HospitalNanjing Medical UniversityJiangsuChina Centre for infection and immunity Studies School of MedicineThe Sun Yat-sen UniversityShenzhen518107GuangdongChina Department of Rheumatology Huashan HospitalFudan UniversityShanghaiChina Department of Pathology and Shenzhen institute of research and Innovation HKU Shenzhen HospitalThe University of Hong KongHong KongChina Centre for Oncology and Immunology Hong Kong Science ParkHong KongChina

B cells are generated in the bone marrow during ontogeny and migrate to peripheral lymphoid organs,where they encounter antigens to elicit humoral *** the past decade,many novel B-cell subsets with distinct phenotypes and functions have been identified,and among these subsets,age-associated B cells(ABCs)were first characterized as a B-cell subset that accumulates with age[1].

关键词： organs lymphoid migrate

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METTL9-catalyzed histidine methylation of S100A9 suppresses the anti-Staphylococcus aureus activity of neutrophils

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Protein & Cell 2024年第3期15卷 223-229页

作者： Dan Cao Mengyue Lv Chi Hu Shukai Li Siwen Wang Chao Xu Wen Pan Department of Digestive Disease The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technologyof ChinaHefei230001China division of Life Sciences and Medicine The CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Basic Medical SciencesInstitute of ImmunologyUniversity of Science and Technology of ChinaHefei 230027China division of Life Sciences and Medicine MOE Key Laboratory for Cellular DynamicsHefei National Center for Cross-Disciplinary SciencesUniversity of Science and Technology of ChinaHefei 230027China

Dear Editor,Protein histidine methylation has been found to be a widespread post-translational modification(PTM)in mammalian cells and represents more than 13%of all protein methylation events in the human methylome(Ning et al.,2016;Kapell and Jakobsson,2021).Recently,we and other groups independently identified METTL9 as the first broad-specificity histidine N1 methyltransferase in mammals(Davydova et al.,2021;Lv et al.,2021).METTL9 methylates a variety of substrates with a common x-His-x-His motif(His is for histidine;the second x is preferably small amino acids:A/C/G/S)and catalyzes methyl transfer to the last histidine.

关键词： S100A9 specificity

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Blockade of CD300A enhances the ability of human NK cells to lyse hematologic malignancies

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Cancer Biology & Medicine 2024年第4期21卷 331-346页

作者： Shuangcheng Li Tianci Wang Xinghui Xiao Xiaodong Zheng Haoyu Sun Rui Sun Hongdi Ma Zhigang Tian Xiaohu Zheng Hefei National research Center for Physical Sciences at Microscale The CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Basic Medical SciencesCenter for Advanced Interdisciplinary Science and Biomedicine of IHMDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China institute of Immunology University of Science and Technology of ChinaHefei 230027China Hefei TG ImmunoPharma Corporation Limited Hefei 230601China research Unit of NK Cell Study Chinese Academy of Medical SciencesBeijing 100864China Key Laboratory of Quantitative Synthetic Biology Shenzhen Institute of Synthetic BiologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China

Objective: The human cluster of differentiation(CD)300A, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, was investigated as a potential immune checkpoint for human natural killer(NK) cells targeting hematologic malignancies(HMs).Methods: We implemented a stimulation system involving the CD300A ligand, phosphatidylserine(PS), exposed to the outer surface of malignant cells. Additionally, we utilized CD300A overexpression, a CD300A blocking system, and a xenotransplantation model to evaluate the impact of CD300A on NK cell efficacy against HMs in in vitro and in vivo settings. Furthermore, we explored the association between CD300A and HM progression in ***: Our findings indicated that PS hampers the function of NK cells. Increased CD300A expression inhibited HM lysis by NK cells. CD300A overexpression shortened the survival of HM-xenografted mice by impairing transplanted NK cells. Blocking PS–CD300A signals with antibodies significantly amplified the expression of lysis function-related proteins and effector cytokines in NK cells, thereby augmenting the ability to lyse HMs. Clinically, heightened CD300A expression correlated with shorter survival and an “exhausted” phenotype of intratumoral NK cells in patients with HMs or solid ***: These results propose CD300A as a potential target for invigorating NK cell-based treatments against HMs.

关键词： NK cell CD300A phosphatidylserine immune checkpoint hematologic malignancy

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Medicinal chemistry strategies towards the development of non-covalent SARS-CoV-2 Mpro inhibitors

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Acta Pharmaceutica Sinica B 2024年第1期14卷 87-109页

作者： Letian Song Shenghua Gao Bing Ye Mianling Yang Yusen Cheng Dongwei Kang Fan Yi Jin-Peng Sun Luis Menéndez-Arias Johan Neyts Xinyong Liu Peng Zhan Department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Shenzhen research institute of Shandong university Shenzhen 518057China The Key Laboratory of infection and immunity of Shandong Province Department of PharmacologySchool of Basic Medical SciencesShandong UniversityJinan 250012China Key Laboratory Experimental Teratology of the Ministry of Education Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Centro de Biologı´a Molecular“Severo Ochoa”(Consejo Superior de Investigaciones Cientı´ficas&Autonomous university of Madrid) Madrid 28049Spain KU Leuven Department of Microbiology and ImmunologyRega Institute for Medical ResearchLaboratory of Virology and ChemotherapyLeuven 3000Belgium

The main protease(M^(pro))of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life *** covalent M^(pro)inhibitor nirmatrelvir(in combination with ritonavir,a pharmacokinetic enhancer)and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic *** antiviral drugs are needed to fight the pandemic,while non-covalent M^(pro)inhibitors could be promising alternatives due to their high selectivity and favorable *** non-covalent M^(pro)inhibitors with desirable properties have been developed based on available crystal structures of M^(pro).In this article,we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent M^(pro)inhibitors,followed by a general overview and critical analysis of the available *** viewpoints and insights into current strategies for the development of non-covalent M^(pro)inhibitors are also discussed.

关键词： COVID-19 SARS-CoV-2 Main protease Non-covalent inhibitors Medicinal chemistry strategies

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Unsynchronized butyrophilin molecules dictate cancer cell evasion of Vγ9Vδ2 T-cell killing

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Cellular & Molecular Immunology 2024年第4期21卷 362-373页

作者： Zeguang Wu Qiezhong Lamao Meichao Gu Xuanxuan Jin Ying Liu Feng Tian Ying Yu Pengfei Yuan Shuaixin Gao Thomas S.Fulford Adam P.Uldrich Catherine C.L Wong Wensheng Wei Biomedical Pioneering Innovation Center Peking-Tsinghua Center for Life SciencesPeking University Genome Editing Research CenterState Key Laboratory of Protein and Plant Gene ResearchSchool of Life SciencesPeking University100871BeijingChina EdiGene Inc. Life Science ParkChangping District102206BeijingChina Center for Precision Medicine Multi-Omics research Peking University Health Science CenterPeking University100191BeijingChina Department of Microbiology and Immunology at the Peter Doherty institute for infection and immunity The University of MelbourneParkvilleVIC3010Australia Cancer Immunology Program Peter MacCallum Cancer CentreMelbourneVICAustralia State Key Laboratory for Complex Severe and Rare DiseasesClinical Research InstitutePeking Union Medical College HospitalChinese Academy of Medical Science&Peking Union Medical CollegePeking-Tsinghua Center for Life Sciences100871BeijingChina

Vγ9Vδ2 T cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate *** our effort to understand how cancer cells evade the cell-killing activity of Vγ9Vδ2 T cells,we performed a comprehensive genome-scale CRISPR screening of cancer *** found that four molecules belonging to the butyrophilin(BTN)family,specifically BTN2A1,BTN3A1,BTN3A2,and BTN3A3,are critically important and play unique,nonoverlapping roles in facilitating the destruction of cancer cells by primary Vγ9Vδ2 T *** coordinated function of these BTN molecules was driven by synchronized gene expression,which was regulated by IFN-γsignaling and the RFX ***,an enzyme called QPCTL was shown to play a key role in modifying the N-terminal glutamine of these BTN proteins and was found to be a crucial factor in Vγ9Vδ2 T cell killing of cancer *** our research,we offer a detailed overview of the functional genomic mechanisms that underlie how cancer cells escape Vγ9Vδ2 T ***,our findings shed light on the importance of the harmonized expression and function of gene family members in modulating T-cell activity.

关键词： Butyrophilin Vγ9Vδ2 T-cell Cancer-specific immune evasion Glutaminyl-peptide cyclotransferase-like Pyrophosphate metabolite Immunotherapy

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SARS-CoV-2 aberrantly elevates mitochondrial bioenergetics to induce robust virus propagation

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2702-2715页

作者： Hye Jin Shin Wooseong Lee Keun Bon Ku Gun Young Yoon Hyun-Woo Moon Chonsaeng Kim Mi-Hwa Kim Yoon-Sun Yi Sangmi Jun Bum-Tae Kim Jong-Won Oh Aleem Siddiqui Seong-Jun Kim Department of Convergent research of Emerging Virus infection Korea Research Institute of Chemical TechnologyDaejeon 34114Republic of Korea Gyeongnam Biohealth research Center Gyeongnam Branch InstituteKorea Institute of ToxicologyJinju 52834Republic of Korea Center for research Equipment Korea Basic Science InstituteCheongjuChungcheongbuk-do 28119Republic of Korea Department of Biotechnology Yonsei UniversitySeoul 03722Republic of Korea division of Infectious Diseases School of MedicineUniversity of CaliforniaSan DiegoLa JollaCA 92093USA Present address:Department of Microbiology Chungnam National University School of MedicineDaejeon 35015Republic of Korea

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a‘highly transmissible respiratory pathogen,leading to severe multiorgan ***,knowledge regarding SARS-CoV-2-induced cellular alterations is *** this study,we report that SARSCoV-2 aberrantly elevates mitochondrial bioenergetics and activates the EGFR-mediated cell survival signal cascade during the early stage of viral ***-CoV-2 causes an increase in mitochondrial transmembrane potential via the SARS-CoV-2 RNAnucleocapsid cluster,thereby abnormally promoting mitochondrial elongation and the OXPHOS process,followed by enhancing ATP ***,SARS-CoV-2 activates the EGFR signal cascade and subsequently induces mitochondrial EGFR trafficking,contributing to abnormal OXPHOS process and viral *** EGFR inhibitors remarkably reduce SARS-CoV-2 propagation,among which vandetanib exhibits the highest antiviral *** of SARS-CoV-2-infected cells with vandetanib decreases SARS-CoV-2-induced EGFR trafficking to the mitochondria and restores SARS-CoV-2-induced aberrant elevation in OXPHOS process and ATP generation,thereby resulting in the reduction of SARS-CoV-2 ***,oral administration of vandetanib to SARS-CoV-2-infected hACE2 transgenic mice reduces SARS-CoV-2 propagation in lung tissue and mitigates SARS-CoV-2-induced lung *** also exhibits potent antiviral activity against various SARS-CoV-2 variants of concern,including alpha,beta,delta and omicron,in in vitro cell culture *** together,our findings provide novel insight into SARS-CoV-2-induced alterations in mitochondrial dynamics and EGFR trafficking during the early stage of viral infection and their roles in robust SARS-CoV-2 propagation,suggesting that EGFR is an attractive host target for combating COVID-19.

关键词： alterations aberrant thereby

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Insights into varicella-zoster virus assembly from the B-and C-capsid at near-atomic resolution structures

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hLife 2024年第2期2卷 64-74页

作者： Lei Cao Nan Wang Zhe Lv Wenyuan Chen Zhonghao Chen Lifei Song Xueyan Sha Guiqiang Wang Yaling Hu Xiaojun Lian Guoliang Cui Jinyan Fan Yaru Quan Hongrong Liu Hai Hou Xiangxi Wang CAS Key Laboratory of infection and immunity National Laboratory of MacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijingChina Key Laboratory for Matter Microstructure and Function of Hunan Province Key Laboratory of Low-dimensional Quantum Structures and Quantum ControlSchool of Physics and ElectronicsHunan Normal UniversityHunanChina institute of Medical research Northwestern Polytechnical UniversityShanxiChina Sinovac(Dalian)Vaccine Technology Co. Ltd.LiaoningChina Sinovac Biotech Ltd. BeijingChina National institutes for Food and Drug Control BeijingChina

Varicella-zoster is a highly communicable virus that can be transmitted through the airborne *** one quarter of people are infected with this *** studies have described the structure of A-capsid and a blurred reconstruction of the C-capsid with icosahedral *** this study,we have determined the more precise detailed structures of the varicella-zoster virus(VZV)B-and C-capsid in icosahedral symmetry using a combination of block-based reconstruction and symmetry relaxation *** addition,we are reporting structural details of the portal vertex reconstructions in five-fold symmetry and portal reconstructions in twelve-fold *** structures unveil the basis for the high thermal stability of the VZV *** conformational flexibility of structural elements of the capsid plays a role in the assembly of the capsid and drives processes critical for the viral life *** results of the study open up new avenues for the development of drugs against a highly prevalent and contagious pathogen.

关键词： varicella-zoster virus capsid structure virus assembly

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Burden of RSV among inpatients with lower respiratory tract infection under 5 years of age: A 10-year retrospective study in Southwest China from 2009 to 2019

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Chinese Medical Journal Pulmonary and Critical Care Medicine 2024年第3期2卷 182-187页

作者： Taoyu Li Heping Fang Xiangyu Liu Yu Deng Na Zang Jun Xie Xiaohong Xie Zhengxiu Luo Jian Luo Yulin Liu Zhou Fu Luo Ren Enmei Liu Department of Respiratory Medicine Children’s Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of Child Rare Diseases in Infection and ImmunityChongqing 400015China Pediatric research institute Children’s Hospital of Chongqing Medical UniversityChongqing 401122China

Objectives:Respiratory syncytial virus(RSV)is a leading cause of lower respiratory tract infection(LRTI).However,few comprehensive descriptions of the disease burden,medical resource utilization(MRU),and costs of RSV are available for *** study aimed to provide the basis for the development of RSV prevention strategies by analyzing the burden of RSV among inpatients with lower respiratory tract infection under 5 years of ***:We conducted a retrospective hospital-based study from June 2009 to May 2019 in *** with LRTI were tested for eight *** analyzed the RSV disease burden,MRU,and direct hospitalization costs by using non-parametric Mann‒Whitney U test,Chi-squared test or Fisher’s exact test and logistic ***:A total of 6991 children under 5 years of age with LRTI were included in this *** overall RSVpositive rate was 34.5%(2410/6991).Prior to admission,81.9%(1973/2410)of these RSV-positive cases were otherwise *** with children aged 24–59 months,the odds ratio(OR)and 95%confidence interval(CI)for RSV infection were 2.509(2.139–2.945),1.882(1.549–2.222),and 1.479(1.240–1.765)for those aged 1–5 months,6–11 months,and 12–23 months,*** proportions of patients treated with invasive ventilation and continuous positive airway pressure(CPAP)were significantly higher among RSV-positive cases(1.1%[27/2410]and 3.9%[93/2410])than RSV-negative cases(0.9%[43/4581]and 2.7%[124/4581])(P=0.023).Compared with RSV-negative cases,RSV-positive cases had significantly longer hospital length of stay(6[5,8]days vs.6[5,8]days,Pinfections occurred during early childhood and among individuals in the otherwise healthy *** age was associated with a higher RSV-positive *** prevention measures are needed in the earliest stages to reduce the RSV burden.

关键词： Respiratory syncytial virus Children Respiratory tract infection Disease burden

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Mpox(formerly monkeypox):pathogenesis,prevention,and treatment

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Signal Transduction and Targeted Therapy 2024年第1期9卷 234-248页

作者： Junjie Lu Hui Xing Chunhua Wang Mengjun Tang Changcheng Wu Fan Ye Lijuan Yin Yang Yang Wenjie Tan Liang Shen Xiangyang Central Hospital Affiliated Hospital of Hubei University of Arts and ScienceHubei ProvinceXiangyang 441021China NHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China College of Biotechnology Tianjin University of Science&TechnologyTianjin 300457China Shenzhen Key Laboratory of Pathogen and immunity National Clinical Research Center for infectious diseaseState Key Discipline of Infectious DiseaseShenzhen Third People’s HospitalSecond Hospital Affiliated to Southern University of Science and TechnologyShenzhen 518112China

In 2022,a global outbreak of Mpox(formerly monkeypox)occurred in various countries across Europe and America and rapidly spread to more than 100 countries and *** World Health Organization declared the outbreak to be a public health emergency of international concern due to the rapid spread of the Mpox ***,nations intensified their efforts to explore treatment strategies aimed at combating the infection and its ***,the available therapeutic options for Mpox virus infection remain *** far,only a few numbers of antiviral compounds have been approved by regulatory *** the high mutability of the Mpox virus,certain mutant strains have shown resistance to existing pharmaceutical *** highlights the urgent need to develop novel antiviral drugs that can combat both drug resistance and the potential threat of ***,there is a lack of comprehensive literature on the pathophysiology and treatment of *** address this issue,we conducted a review covering the physiological and pathological processes of Mpox infection,summarizing the latest progress of anti-Mpox *** analysis encompasses approved drugs currently employed in clinical settings,as well as newly identified small-molecule compounds and antibody drugs displaying potential antiviral efficacy against ***,we have gained valuable insights from the process of Mpox drug development,including strategies for repurposing drugs,the discovery of drug targets driven by artificial intelligence,and preclinical drug *** purpose of this review is to provide readers with a comprehensive overview of the current knowledge on Mpox.

关键词： prevention treatment intensified

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