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H7N9 virus infection triggers lethal cytokine storm by activating gasdermin E-mediated pyroptosis of lung alveolar epithelial cells

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National Science Review 2022年第1期9卷 47-55页

作者： Xiaopeng Wan Jiqing Li Yupeng Wang Xiaofei Yu Xijun He Jianzhong Shi Guohua Deng Xianying Zeng Guobin Tian Yanbing Li Yongping Jiang Yuntao Guan Chengjun Li Feng Shao Hualan Chen State Key laboratory of veterinary biotechnology Harbin Veterinary Research Institute Chinese Academy of Agricultural Sciences National Institute of Biological Sciences

The H7 N9 influenza virus emerged in China in 2013,causing more than 1560 human infections,39% of which were fatal.A ’cytokine storm’ in the lungs of H7 N9 patients has been linked to a poor prognosis and death;however,the underlying mechanism that triggers the cytokine storm is ***,we found that efficient replication of the H7 N9 virus in mouse lungs activates gasdermin E(GSDME)-mediated pyroptosis in alveolar epithelial cells,and that the released cytosolic contents then trigger a cytokine *** of Gsdme switched the manner of death of A549 and human primary alveolar epithelial cells from pyroptosis to apoptosis upon H7 N9 virus infection,and Gsdme knockout mice survived H7 N9 virus lethal *** findings reveal that GSDME activation is a key and unique mechanism for the pulmonary cytokine storm and lethal outcome of H7 N9 virus infection and thus opens a new door for the development of antivirals against the H7 N9 virus.

关键词： H7N9 virus cytokine storm gasdermin E pyroptosis

Isolation and characterization of H7N9 viruses from live poultry markets--Implication of the source of current H7N9 infection in humans

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Chinese Science Bulletin 2013年第16期58卷 1857-1863页

作者： SHI JianZhong DENG GuoHua LIU PeiHong ZHOU JinPing GUAN LiZheng LI WenHui LI XuYong GUO Jing WANG GuoJun FAN Jun WANG JinLiang LI YuanYuan JIANG YongPing LIU LiLing TIAN GuoBin LI ChengJun CHEN HuaLan Animal Influenza laboratory State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research Institute Chinese Academy of Agricultural Sciences Shanghai Animal Disease Control Center

On March 31, 2013, the National Health and Family Planning Commission announced that human infections with a previously undescribed influenza A (H7N9) virus had occurred in Shanghai and Anhui Province, China. To investigate the possible origins of the H7N9 viruses causing these human infections, we collected 970 samples, including drinking water, soil, and cloacal and tracheal swabs of poultry from live poultry markets and poultry farms in Shanghai and Anhui Province. Twenty samples were positive for the H7N9 influenza virus. Notably, all 20 viruses were isolated from samples collected from live poultry markets in Shanghai. Phylogenetic analyses showed that the six internal genes of these novel human H7N9 viruses were derived from avian H9N2 viruses, but the ancestor of their HA and NA genes is uncertain. When we examined the phylogenetic relationship between the H7N9 isolates from live poultry markets and the viruses that caused the human infections, we found that they shared high homology across all eight gene segments. We thus identified the direct avian origin of the H7N9 influenza viruses that caused the human infections. Importantly, we observed that the H7N9 viruses isolated from humans had acquired critical mutations that made them more "human-like". It is therefore imperative to take strong measures to control the spread of H7N9 viruses in birds and humans to prevent further threats to human health.

关键词：流感病毒人类感染市场活禽分离感染源鉴定蕴涵

Role of copper chelating agents: between old applications and new perspectives in neuroscience

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Neural Regeneration Research 2025年第3期20卷 751-762页

作者： Rosalba Leuci Leonardo Brunetti Vincenzo Tufarelli Marco Cerini Marco Paparella Nikola Puvača Luca Piemontese Department of Pharmacy-Pharmaceutical Science University of Bari Aldo MoroBariItaly Department of Precision and Regenerative Medicine and Jonian Area(DiMePRe-J) Section of Veterinary Science and Animal ProductionUniversity of Bari Aldo MoroBariItaly Department of Engineering Management in biotechnology Faculty of Economics and Engineering Management in Novi SadUniversity Business Academy in Novi SadNovi SadSerbia

The role of copper element has been an increasingly relevant topic in recent years in the fields of human and animal health, for both the study of new drugs and innovative food and feed supplements. This metal plays an important role in the central nervous system, where it is associated with glutamatergic signaling, and it is widely involved in inflammatory processes. Thus, diseases involving copper(Ⅱ) dyshomeostasis often have neurological symptoms, as exemplified by Alzheimer's and other diseases(such as Parkinson's and Wilson's diseases). Moreover, imbalanced copper ion concentrations have also been associated with diabetes and certain types of cancer, including glioma. In this paper, we propose a comprehensive overview of recent results that show the importance of these metal ions in several pathologies, mainly Alzheimer's disease, through the lens of the development and use of copper chelators as research compounds and potential therapeutics if included in multi-target hybrid drugs. Seeing how copper homeostasis is important for the well-being of animals as well as humans, we shortly describe the state of the art regarding the effects of copper and its chelators in agriculture, livestock rearing, and aquaculture, as ingredients for the formulation of feed supplements as well as to prevent the effects of pollution on animal productions.

关键词： agriculture Alzheimer's disease chelators copper feed supplements multi-target

Proviral genomic sequence analysis of Chinese donkey leukocyte attenuated equine infectious anemia virus vaccine and its parental virus strain Liaoning

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Science China(Life Sciences) 2002年第1期45卷 57-67页

作者：王柳杨志彪王玫童光志仇华吉刘红全孔宪刚 National Key laboratory of veterinary biotechnology Harbin Veterinary Research Institute Chinese Academy of Agricultural Sciences Harbin China

Proviral DNA was extracted from donkey leukocyte infected with Chinese donkey leukocyte attenuated equine infectious anemia virus(DLA-EIAV), and peripheral blood lymphocytes(PBL) from a horse infected with the virulent EIAV strain Liaoning(EIAV L). The entire proviral DNA from both viruses was cloned and sequenced. The lengths of complete genomic sequences of DLA-EIAV and EIAV L provirus were 8266 bp and 8235 bp, respectively. Sequence comparison indicated that DLA-EIAV shares 97.0% and 97.5% in sequence homology with EIAV L and donkey-adapted EIAV(DA-EIAV), respectively. Lots of variations occurred in long terminal repeat(LTR, consisting of U3, R, U5), ORF S2, and env regions between DLA-EIAV and EIAV L. The nucleotide sequence differences of the two viruses in U3, R, U5, ORF S2, and env are 13.2%, 7.5%, 5.1%, 3.9%, and 2.7%, respectively, and predicted amino acid sequence differences in env and S2 coding regions are 4.4% and 8.8%, respectively. Six conserved regions are characterized in Gp90. There is a cis-activating GATA motif in ENH of DLA-EIAV and EIAV L. Two N-linked glycosylation sites disappeared in DLA-EIAV Gp90 in comparison with that of EIAV L. A bHLH transcription factor binding consensus sequence was found in LTR of DLA-EIAV but not in EIAV L. Furthermore, there is a mutation in the stem of DLA-EIAV TAR resulting in formation of a uridine tuber. Further study is needed to uncover the relationship between sequence changes and their biological functions of DLA-EIAV and L.

关键词： equine infectious anemia virus(EIAV), donkey leukocyte attenuated(DLA) strain, L strain, sequence analysis.

Continued evolution of the Eurasian avian-like H1N1 swine influenza viruses in China

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Science China(Life Sciences) 2023年第2期66卷 269-282页

作者： Fei Meng Yan Chen Zuchen Song Qiu Zhong Yijie Zhang Chuanling Qiao Cheng Yan Huihui Kong Liling Liu Chengjun Li Huanliang Yang Hualan Chen State Key laboratory of veterinary biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China

Animal influenza viruses continue to pose a threat to human public health. The Eurasian avian-like H1N1(EA H1N1) viruses are widespread in pigs throughout Europe and China and have caused human infections in several countries, indicating their pandemic potential. To carefully monitor the evolution of the EA H1N1 viruses in nature, we collected nasal swabs from 103,110pigs in 22 provinces in China between October 2013 and December 2019, and isolated 855 EA H1N1 viruses. Genomic analysis of 319 representative viruses revealed that these EA H1N1 viruses formed eight different genotypes through reassortment with viruses of other lineages circulating in humans and pigs, and two of these genotypes(G4 and G5) were widely distributed in *** studies indicated that some strains have become highly pathogenic in mice and highly transmissible in ferrets via respiratory droplets. Moreover, two-thirds of the EA H1N1 viruses reacted poorly with ferret serum antibodies induced by the currently used H1N1 human influenza vaccine, suggesting that existing immunity may not prevent the transmission of the EA H1N1 viruses in humans. Our study reveals the evolution and pandemic potential of EA H1N1 viruses and provides important insights for future pandemic preparedness.

关键词： H1N1 influenza immunity

Vaccination of poultry successfully eliminated human infection with H7N9 virus in China

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Science China(Life Sciences) 2018年第12期61卷 1465-1473页

作者： Xianying Zeng Guobin Tian Jianzhong Shi Guohua Deng Chengjun Li Hualan Chen State Key laboratory of veterinary biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China

The H7 N9 viruses that emerged in China in 2013 were nonpathogenic in chickens but mutated to a highly pathogenic form in early 2017 and caused severe disease outbreaks in chickens. The H7 N9 influenza viruses have caused five waves of human infection, with almost half of the total number of human cases(766 of 1,567) being reported in the fifth wave, raising concerns that even more human infections could occur in the sixth wave. In September 2017, an H5/H7 bivalent inactivated vaccine for chickens was introduced, and the H7 N9 virus isolation rate in poultry dropped by 93.3% after vaccination. More importantly,only three H7 N9 human cases were reported between October 1, 2017 and September 30, 2018, indicating that vaccination of poultry successfully eliminated human infection with H7 N9 virus. These facts emphasize that active control of animal disease is extremely important for zoonosis control and human health protection.

关键词： H7N9 influenza virus evolution vaccination human infection elimination

Next-generation sequencing and single-cell RT-PCR reveal a distinct variable gene usage of porcine antibody repertoire following PEDV vaccination

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Science China(Life Sciences) 2020年第8期63卷 1240-1250页

作者： Ren Li Fang Fu Li Feng PingHuang Liu State Key laboratory of veterinary biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150001China

Porcine epidemic diarrhea virus(PEDV)is the most common diarrhea-causing pathogen in newborn *** clarifications of the overall antibody repertoire and antigen-specific antibody repertoire are essential to provide important insights into the B-cell response and reshape new ***,we applied next-generation sequencing(NGS)technology to investigate immunoglobulin(Ig)variable(V)gene segment usage of swine B-cells from peripheral blood lymphocytes(PBL)and mesenteric lymph node(MLN)cells following PEDV *** identified the transcripts of all functional Ig V-genes in antibody ***1 S2,IgKV1-11,and IgLV3-4 were the most prevalent gene segments for heavy,kappa,and lambda chains,respectively,in PBL and *** previous studies,IgKV1,instead of IgKV2,and IgLV3,instead of IgLV8,were the prevalent Ig V-gene families for kappa and lambda light chains,*** further examined the antibody repertoire of PEDV spike-specific B cells by single-cell *** contrast to the overall antibody repertoire,Ig V-gene segments of PEDV spike-specific B cells preferentially adopted IgHV1-4 and IgHV1-14 for heavy chain,IgKV1-11 for kappa chain,and IgLV3-3 for lambda *** results represent a comprehensive analysis to characterize the Ig V-gene segment usage in the overall and PEDV spike-specific antibody repertoire in PBL and MLN.

关键词： porcine epidemic diarrhea virus(PEDV) next-generation sequencing(NGS) single-cell RT-PCR antibody repertoire

TRIM35 mediates protection against influenza infection by activating TRAF3 and degrading viral PB2

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Protein & Cell 2020年第12期11卷 894-914页

作者： Nan Sun Li Jiang Miaomiao Ye Yihan Wang Guangwen Wang Xiaopeng Wan Yuhui Zhao Xia Wen Libin Liang Shujie Ma Liling Liu Zhigao Bu Hualan Chen Chengjun Li State Key laboratory of veterinary biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China

Tripartite motif(TRIM)family proteins are important effectors of innate immunity against viral *** we identified TRIM35 as a regulator of TRAF3 *** in or inhibition of TRIM35 suppressed the production of type I interferon(IFN)in response to viral infection.777m35-deficient mice were more susceptible to influenza A virus(IAV)infection than were wild-type ***35 promoted the RIG-Imediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and *** PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of ***35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2,thereby antagonizing its suppression of TRAF3 *** in vitro and in vivo findings thus reveal novel roles of TRIM35,through catalyzing Lys63-or Lys48-linked polyubiquitination,in RIG-I antiviral immunity and mechanism of defense against IAV infection.

关键词： influenza A virus PB2 TRIM35 TRAF3 ubiquitination antiviral immunity

Mycoplasma leachii causes bovine mastitis: Evidence from clinical symptoms,histopathology and immunohistochemistry

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Journal of Integrative Agriculture 2019年第1期18卷 160-168页

作者： CHANG Ji-tao YU De-bin LIANG Jian-bin CHEN Jia WANG Jian-fa WANG Fang JIANG Zhi-gang HE Xi-jun WU Rui YU Li Division of Livestock Infectious Diseases/State Key laboratory of veterinary biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural Sciences College of Animal Science and veterinary Medicine Heilongjiang Bayi Agricultural University (Daqing High-tech Industrial Development Zone) Pathology laboratory/State Key laboratory of veterinary biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural Sciences

Twelve quarters of six lactating cows were inoculated with Mycoplasma leachii strain GN407 through intramammary ductal infusion; another 12 quarters were inoculated with heat-inactivated *** culture medium as negative *** procedures,including clinical assessment,etiology assessment,pathology and immunohistochemistry(IHC),were used to elucidate the pathogenicity of *** in bovine *** post-inoculation days(PIDs) 3 to 9,12 inoculated quarters developed mild to severe clinical mastitis and mammary tissue histopathological changes,including inflammatory cell infiltration and architectural destruction of mammary gland *** *** antigen was also detected by IHC in the mammary gland epithelial cells of the inoculated quarters as a weak signal on PID 6 and as a strong signal on PID *** control quarters also developed mild mastitis and histopathological changes on PID 9,and *** was also detected by *** the experimental period,the quarters of the negative control cow were clinically and pathologically normal,and the *** antigen was not *** conclusion,direct histological and immunohistochemical evidence confirmed that *** causes clinical bovine mastitis through histopathological lesions induced by invasion of the pathogen into mammary gland cells and through inflammatory cell infiltration.

关键词： Mycoplasma leachii bovine mastitis pathogenicity histopathology immunohistochemistry