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Fulminant myocarditis induced by SARS-CoV-2 infection without severe lung involvement:insights into COvID-19 pathogenesis

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Journal of Genetics and Genomics 2024年第6期51卷 608-616页

作者： Han Du Zhongtao Du Liang Wang Hong Wang Mingjun Jia Chunge Zhang Yun Liu Cheng Zhang Ya Zhang Ruifeng Zhang Shuang Zhang Ning Zhang Zhenghai Ma Chen Chen Wenjun Liu Hui Zeng George F.Gao Xiaotong Hou Yuhai Bi College of Life Science and Technology Xinjiang UniversityUrumchiXinjiang 830046China CAS Key Laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyCenter for Influenza Research and Early-warning(CASCIRE)CAS-TWAS Center of Excellence for Emerging Infectious Diseases(CEEID)Chinese Academy of SciencesBeijing 100101China Bejing Anzhen Hospital Capital Medical UniversityBeijing 100029China College of Veterinary Medicine Shanxi Agricultural UniversityTaiyuanShanxi 030031China University of Chinese Academy of Sciences Bejing 100049China Beijing Shijitan Hospital Capital Medical UniversityBeijing 100038China

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection often leads to pulmonary complications.Cardiovascular sequelae,including myocarditis and heart failure,have also been reported.Here,the study presents two fulminant myocarditis cases infected by SARS-CoV-2 exhibiting remarkable elevation of cardiac biomarkers without significant pulmonary injury,as determined by imaging examinations.Immunohistochemical staining reveals the viral antigen within cardiomyocytes,indicating that SARSCoV-2 could directly infect the myocardium.The full viral genomes from respiratory,anal,and myocardial specimens are obtained via next-generation sequencing.Phylogenetic analyses of the whole genome and spike gene indicate that viruses in the myocardium/pericardial effusion and anal swabs are closely related and cluster together yet diverge from those in the respiratory samples.In addition,unique mutations are found in the anal/myocardial strains compared to the respiratory strains,suggesting tissue-specific virus mutation and adaptation.These findings indicate genetically distinct SARS-CoV-2 variants have infiltrated and disseminated within myocardial tissues,independent of pulmonary injury,and point to different infection routes between the myocardium and respiratory tract,with myocardial infections potentially arising from intestinal infection.These findings highlight the potential for systemic SARS-CoV-2 infection and the importance of a thorough multi-organ assessment in patients for a comprehensive understanding of thepathogenesisof COVID-19.

关键词： COVID-19 SARS-CoV-2 Fulminant myocarditis Myocardium Infection

influenza and pneumococcal vaccination coverage and associated factors in patients hospitalized with acute exacerbations of COPD in China: Findings from real-world data

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中华医学杂志(英文版) 2024年第10期137卷 1179-1189页

作者： He Ruoxi Ren Xiaoxia Huang Ke Lei Jieping Niu Hongtao Li Wei Dong Fen Li Baicun Wang Ye Yang Ting Wang Chen School of Population Medicine and Public Health Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Department of Respiratory Medicine National Key Clinical Specialty Branch of National Clinical Research Center for Respiratory Disease Xiangya Hospital Central South University Changsha Hunan China Department of Pulmonary and Critical Care Medicine Center of Respiratory Medicine China-Japan Friendship Hospital Beijing China Institute of Respiratory Medicine Chinese Academy of Medical Sciences Beijing China National center for Respiratory Medicine Beijing China National Clinical research center for Respiratory Diseases Beijing China Department of Clinical research and Data Management Center of Respiratory Medicine China-Japan Friendship Hospital Beijing China

Background: influenza and pneumococcal vaccination are a priority in patients with chronic obstructive pulmonary disease (COPD). However, limited information is available on vaccination coverage among patients with acute exacerbations of COPD (AECOPD) in China. This study aimed to determine the rates and associated factors of influenza and pneumococcal vaccination in patients hospitalized with AECOPD.Methods: Baseline data from a national, multicenter, hospital-based study that included adult inpatients with AECOPD between 2017 and 2021 were analyzed. The outcomes of interest were the influenza vaccination in the past year and the pneumococcal vaccination in the past 5 years. To ensure national representativeness, rates were weighted according to the distribution of hospital levels and types enrolled in this study. Multivariable Poisson regression based on mixed-effects models were used to determine the associated factors. The independent variables included the region and hospital features where the participants were located, sociodemographic characteristics (age, sex, rural/urban residence, education, etc.), and clinical indicators (COPD disease history, lung function parameters, comorbidities, etc.). The treatment profiles of the vaccinated and unvaccinated participants were compared.Results: Of 6949 eligible participants, the weighted rates of influenza/pneumococcal, influenza, and pneumococcal vaccination were 2.72% (95% confidence interval [CI]: 2.34%-3.10%), 2.09% (95% CI: 1.76%-2.43%), and 1.25% (95% CI: 0.99%-1.51%), respectively. In multivariable models, age ≥60 years (60-69 years, odds ratio [OR]: 1.90, 95% CI: 1.11-3.25; ≥80 years, OR: 2.00, 95% CI: 1.06-3.78), geographical regions (Northern China relative to Eastern China, OR: 5.09, 95% CI: 1.96-13.21), urban residence (OR: 1.69, 95% CI: 1.07-2.66), a higher education level (junior high school, OR: 1.77, 95% CI: 1.21-2.58; senior high school or above, OR: 2.61, 95% CI: 1.69-4.03), former smoking (OR: 1.79, 95% CI: 1.15-2.79), and regular inhaled medic

关键词： Chronic obstructive pulmonary disease influenza Pneumococcal Vaccine AECOPD

C1QTNF5 is a novel attachment factor that facilitates the entry of influenza A virus

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Virologica Sinica 2024年第2期39卷 277-289页

作者： Lei Yu Xinjin Liu Xiaoqin Wei Junrui Ren Xueyun Wang Shuwen Wu Ke Lan State Key Laboratory of Virology Medical Research InstituteCollege of Life SciencesWuhan UniversityWuhan430072China Frontier Science center for Immunology and Metabolism Wuhan UniversityWuhan430072China Taikang center for Life and Medical Sciences Wuhan UniversityWuhan430072China

influenza A virus(IAV)binds sialic acid receptors on the cell surface to enter the host cells,which is the key step in initiating infection,transmission and pathogenesis.Understanding the factors that contribute to the highly efficient entry of IAV into human cells will help elucidate the mechanism of viral entry and pathogenicity,and provide new targets for intervention.In the present study,we reported a novel membrane protein,C1QTNF5,which binds to the hemagglutinin protein of IAV and promotes IAV infection in vitro and in vivo.We found that the HA1 region of IAV hemagglutinin is critical for the interaction with C1QTNF5 protein,and C1QTNF5 interacts with hemagglutinin mainly through its N-terminus(1–103 aa).In addition,we further demonstrated that overexpression of C1QTNF5 promotes IAV entry,while blocking the interaction between C1QTNF5 and IAV hemagglutinin greatly inhibits viral entry.However,C1QTNF5 does not function as a receptor to mediate IAV infection in sialic acid-deficient CHO-Lec2 cells,but promotes IAV to attach to these cells,suggesting that C1QTNF5 is an important attachment factor for IAV.This work reveals C1QTNF5 as a novel IAV attachment factor and provides a new perspective for antiviral strategies.

关键词： C1QTNF5 influenza A virus Viral entry Hemagglutinin Attachment factor

Inactivated H9N2 vaccines developed with early strains do not protect against recent H9N2 viruses:Call for a change in H9N2 control policy

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Journal of Integrative Agriculture 2024年第6期23卷 2144-2148页

作者： Yanjing Liu Qingqing Yu Xiangyu Zhou Wenxin Li Xinwen He Yan Wang Guohua Deng Jianzhong Shi Guobin Tian Xianying Zeng Hualan Chen College of Veterinary Medicine Gansu Agricultural UniversityLanzhou 730070China State Key Laboratory for Animal Disease Control and Prevention Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry DiseasesMinistry of Agriculture and Rural Affairs/Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150009China National Poultry Laboratory Animal Resource center Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150009China Harbin Weike Biotechnology Co. Ltd.Harbin 150009China

H9N2 virus has been widely distributed in wild birds and poultry around the world since its first emergence in the United States of America in 1966(Gu et al.2017;Carnaccini and Perez 2020).The virus appeared in chickens in China in the early 1990s,and over the last two decades has gradually become the dominant epidemic subtype(Sun and Liu 2015;Bi et al.2020).Although H9N2 virus infection alone cannot cause severe disease or death in poultry,H9N2 virus-infected birds experience a degree of egg production drop and can be easily infected by other pathogens,thus causing economic losses for poultry industry.

关键词： H9N2 poultry policy

Epidemiological features of seasonal influenza transmission among 11 climate zones in Chinese mainland

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Infectious Diseases of Poverty 2024年第1期13卷 27-41页

作者： Xiaohan Si Liping Wang Kerrie Mengersen Wenbiao Hu Ecosystem Change and Population Health research Group School of Public Health and Social WorkQueensland University of TechnologyBrisbaneQLD 4059Australia Information center Chinese Center for Disease Control and PreventionBeijing 102206China School of Mathematical Sciences Queensland University of TechnologyBrisbaneQLD 4000Australia

Background Previous studies provided some evidence of meteorological factors influence seasonal influenza transmission patterns varying across regions and latitudes.However,research on seasonal influenza activities based on climate zones are still in lack.This study aims to utilize the ecological-based Koppen Geiger climate zones classif-cation system to compare the spatial and temporal epidemiological characteristics of seasonal influenza in Chinese mainland and assess the feasibility of developing an early warning system.Methods Weekly influenza cases number from 2014 to 2019 at the county and city level were sourced from China National Notifiable Infectious Disease Report Information System.Epidemic temporal indices,time series seasonality decomposition,spatial modelling theories including Moran's/and local indicators of spatial association were applied to identify the spatial and temporal patterns of influenza transmission.Results All climate zones had peaks in Winter-Spring season.Arid,desert,cold(BWk)showed up the first peak.Only Tropical,savannah(Aw)and Temperate,dry winter with hot summer(Cwa)zones had unique summer peak.Temper-ate,no dry season and hot summer(Cfa)zone had highest average incidence rate(IR)at 1.047/100,000.The Global Moran's/showed that average IR had significant clustered trend(z=53.69,Pinfluenza exhibited distinct spatial and temporal patterns in different climate zones.Seasonal influenza primarily emerged in BWk,subsequently in Cfa and Cwa.Cfa,Cwa and BSk pose high risk for seasonal influ-enza epidemics.The research finds will provide scientific evidence for developing seasonal infl

关键词： Seasonal influenza Koppen Geiger climate zones classification system Chinese mainland Seasonality decomposition Local indicators of spatial association

Crystal structures of RNA-dependent RNA polymerases from Jingmen tick virus and Alongshan virus

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hLife

hLife 2024年第1期2卷 18-31页

作者： Zhenyang Liu Qi Peng Pu Han Lu Kuai Jianxun Qi Yi Shi CAS Key Laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijingChina Beijing Life Science Academy BeijingChina International Institute of Vaccine research and Innovation Savaid Medical SchoolUniversity of Chinese Academy of SciencesBeijingChina center for influenza research and Early-warning CAS-TWAS Center of Excellence for Emerging Infectious DiseaseChinese Academy of SciencesBeijingChina research Unit of Adaptive Evolution and Control of Emerging Viruses Chinese Academy of Medical SciencesBeijingChina

Jingmenviruses are a group of flavi-like viruses with segmented genome and have been found in various types of hosts,including humans,cattle,monkeys,bats,rodents,sheep,ticks,mosquitoes and nematodes.Jingmenviruses,including the Jingmen tick virus(JMTV)and Alongshan virus(ALSV),have been associated with febrile illness and flu-like symptoms in humans.Viral polymerase plays critical roles in genome replication and transcription and is an ideal target for antiviral drugs.Here,we determined the crystal structures of RNA-dependent RNA polymerase(RdRp)domains of JMTV and ALSV at 2.6Åand 3.2Åresolutions,respectively.The overall structures of JMTV and ALSV RdRp domains are similar to those from the typical unsegmented viruses in Flaviviridae family,especially the Flavivirus genus.JMTV and ALSV RdRps can be divided into three subdomains and the catalytical Motif A-G are conserved like the typical flaviviruses,whereas the zinc-binding pockets are absent from the JMTV and ALSV RdRps.The 50-ends of jingmenvirus genomes are varied in length and sequence,and a highly conserved 8-nucleotide element located on the tip of stem loop A was identified and shown to be required for binding with RdRp and performing de novo replication activity.These findings provide important structural insights into RdRp of segmented flavivirus and reveal the key region of virus genome responsible for replication initiation,which would promote molecular understanding of segmented flavivirus replication and the structure-based design of antiviral drugs against flaviviruses.

关键词： Jingmenviruses X-rays RNA-dependent RNA polymerase replication

Establishment of a humanized ST6GAL1 mouse model for influenza research

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Animal Models and Experimental Medicine 2024年第3期7卷 337-346页

作者： Lyu Chao Han Feng Gao Qian Lv Limin Lu Ziwei Lu Shuangshuang Li Xiaoyan Hu Yuechao Yang Mengjie Zhao Yingze Liu Jun Lu Xuancheng Duo Shuguang National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases Chinese Center for Disease Control and PreventionBeijingChina Institute of Zoology Chinese Academy of SciencesBeijingChina NHC Key Laboratory of Biosafety National Key Laboratory of Intelligent Tracking and Forecasting for Infectious DiseasesNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina Zhejiang Provincial Key Laboratory of Medical Genetics Key Laboratory of Laboratory MedicineMinistry of EducationSchool of Laboratory Medicine and Life SciencesWenzhou Medical UniversityWenzhouChina

Background:This study aimed to construct and characterize a humanized influenza mouse model expressing hST6GAL1.Methods:Humanized fragments,consisting of the endothelial cell-specific K18 promoter,human ST6GAL1-encoding gene,and luciferase gene,were microinjected into the fertilized eggs of mice.The manipulated embryos were transferred into the oviducts of pseudopregnant female mice.The offspring were identified using PCR.Mice exhibiting elevated expression of the hST6GAL1 gene were selectively bred for propagation,and in vivo analysis was performed for screening.Expression of the humanized gene was tested by performing immunohistochemical(IHC)analysis.Hematologic and biochemical analyses using the whole blood and serum of humanized hST6GAL1 mice were performed.Results:Successful integration of the human ST6GAL1 gene into the mouse genome led to the overexpression of human SiaT ST6GAL1.Seven mice were identified as carrying copies of the humanized gene,and the in vivo analysis indicated that hST6GAL1gene expression in positive mice mirrored influenza virus infection characteristics.The IHC results revealed that hST6GAL1 was expressed in the lungs of humanized mice.Moreover,the hematologic and biochemical parameters of the positive mice were within the normal range.Conclusion:A humanized influenza mouse model expressing the hST6GAL1 gene was successfully established and characterized.

关键词： hST6GAL1 humanized mice influenza animal model

research progress in human infection with avian influenza H7N9 virus

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Science China(Life Sciences) 2017年第12期60卷 1299-1306页

作者： Jing Tang Dayan Wang National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and Prevention WHO Collaborating center for Reference and research on influenza Key Laboratory for Medical Virology National Health and Family Planning CommissionBeijing 102206China

Since the identification of the novel reassortant avian influenza A(H7N9) virus in China in 2013, until Jun 30, 2017, the virus has caused five epidemic waves leading to a total of 1,552 human infections, with a fatality rate of about 40%. In the spring of2017, highly pathogenic avian influenza(HPAI) H7N9 virus emerged and has caused 25 human infections. The HPAI H7N9 virus has some biological differences from the LPAI one, such as its multiple basic amino acid residues on HA leading to its independence on trypsin for replication. The pathogenicity of the HPAI H7N9 virus to experimental animals or humans is still unclear. A(H7N9) vaccine development for pandemic preparedness is ongoing, including the reassortment(H7N9/PR8)reverse genetic based vaccine, the virus like particle(VLP) vaccine, the intranasal live attenuated influenza vaccine(LAIV),the non-adjuvant Vero cell culture-derived inactivated whole-virus vaccine, the MDCK culture-derived vaccine, the H7 DNA vaccine and the recombinant replicative H7N9 virus \(H7N9-53 TM\) vaccine. Five neuramidinase resistant sites of A(H7N9)virus isolated from patients have been reported. Some alternative drugs have been studied, such as DAS181(Fludase), ribavirin,troglitazone and minocycline. Persistent surveillance and enhanced global control are essential to fight against human infections with A(H7N9) virus.

关键词： influenza A(H7N9) virus epidemiology virological characteristics vaccine drug resistance

High-Value-Added Utilization of Turpentine:Screening of Anti-influenza Virus Agents fromβ-Pinene Derivatives

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Journal of Renewable Materials 2024年第1期12卷 45-56页

作者： Yiwen Li Hongyan Si Peng Wang Hai Luo Minggui Shen Xiaoping Rao Zhanqian Song Shibin Shang Zongde Wang Shengliang Liao East China Woody Fragrance and Flavor Engineering research center of National Forestry and Grassland Administration Camphor Engineering Research Center of National Forestry and Grassland AdministrationCollege of ForestryJiangxi Agricultural UniversityNanchang330045China Institute of Chemical Industry of Forestry Products China Academy of ForestryNational Engineering Laboratory for Biomass Chemical UtilizationKey and Open Laboratory of Forest Chemical EngineeringState Forestry AdministrationKey Laboratory of Biomass Energy and MaterialJiangsu ProvinceNanjing210042China College of Chemical Engineering Huaqiao UniversityXiamen361021China

Turpentine is a renewable and resourceful forest product.The deep processing and utilization of turpentine,particularly its primary componentβ-pinene,has garnered widespread attention.This study aimed to synthesize 40 derivatives ofβ-pinene,including nopinone,3-cyanopyridines of nopinone,myrtanyl acid,myrtanyl acylthioureas,and myrtanyl amides.We assessed the antiviral activities of theseβ-pinene derivatives against influenza virus A/Puerto Rico/8/34(H1N1)using the 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method.Theβ-pinene derivatives were used before and after cellular infection with the influenza virus to evaluate their preventive and therapeutic effects against the H1N1 virus.The results showed that only compound 10o exhibited a preventive effect against the H1N1 virus with a half-maximal inhibitory concentration(IC50)value of 47.6μmol/L.Among the compounds,4e,4i,and 4l demonstrated therapeutic effects against cellular infection,with compound 4e displaying the most potent therapeutic effect(IC50=17.5μmol/L),comparable to the positive control ribavirin.These findings indicated that certainβ-pinene derivatives exhibited in vitro antiviral activity against the H1N1 influenza A virus,warranting further investigation as potential anti-influenza agents.

关键词： Antiviral activity β-pinene derivative 3-cyanopyridine influenza virus