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Identification of African swine fever virus MGF505-2R as a potent inhibitor of innate immunity in vitro

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Virologica Sinica 2023年第1期38卷 84-95页

作者： Huaguo Huang Wen Dang Zhengwang Shi Mingyang Ding Fan Xu Tao Li Tao Feng Haixue Zheng Shuqi Xiao College of veterinary medicine Northwest A&F UniversityYangling712100China State Key Laboratory of veterinary Etiological Biology College of Veterinary MedicineLanzhou UniversityLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou730046China College of veterinary medicine Gansu Agricultural UniversityLanzhou730070China

African swine fever(ASF)is etiologically an acute,highly contagious and hemorrhagic disease caused by African swine fever virus(ASFV).Due to its genetic variation and phenotypic diversity,until now,no efficient commercial vaccines or therapeutic options are available.The ASFV genome contains a conserved middle region and two flexible ends that code for five multigene families(MGFs),while the biological functions of the MGFs are not fully characterized.Here,ASFV MGF505-2R-deficient mutant ASFV-Δ2R was constructed based on a highly virulent genotype II field isolate ASFV CN/GS/2018 currently circulating in China.Transcriptomic profiling demonstrated that ASFV-Δ2R was capable of inducing a larger number of differentially expressed genes(DEGs)compared with ASFV CN/GS/2018.Hierarchical clustering of up-regulated DEGs revealed that ASFV-Δ2R induced the most dramatic expression of interferon-related genes and inflammatory and innate immune genes,as further validated by RT-qPCR.The GO and KEGG pathway analysis identified significantly enriched pathways involved in pathogen recognition and innate antiviral immunity.Conversely,pharmacological activation of those antiviral immune responses by exogenous cytokines,including type I/II IFNs,TNF-αand IL-1β,exerted combinatory effects and synergized in antiviral capacity against ASFV replication.Collectively,MGF505-2R is a newly identified inhibitor of innate immunity potentially implicated in immune evasion.

关键词： African swine fever virus(ASFV) Multigene families(MGFs) MGF505-2R Differentially expressed genes(DEGs)

Emergence of H5N8 avian influenza virus in domestic geese in a wild bird habitat,Yishui Lake,north central China

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Virologica Sinica 2023年第1期38卷 157-161页

作者： Cheng Zhang Zhong-Yi Wang Huan Cui Li-Gong Chen Chun-Mao Zhang Zhao-Liang Chen Shi-Shan Dong Kui Zhao Ying-Ying Fu Ju-Xiang Liu Zhen-Dong Guo Changchun veterinary Research institute at chinese Academy of Agriculture Sciences Changchun 130122China Beijing institute of Biotechnology Beijing 100071China College of veterinary medicine at Jilin University Changchun 130062China College of veterinary medicine at Hebei Agricultural University Baoding 071000China

Dear Editor,China is located in the eastern part of the Eurasian continent,with a large north–south range,resulting in a large temperature difference.Wild birds migrate two times annually along with the north–south range,including eastern,central and western routes in China.Wild birds are reported to carry influenza viruses from multiple sources,causing the virus to spread across a wide range of regions,which present great challenges for the prevention and control of avian influenza viruses(AIVs)(He et al.,2021;Shi and Gao,2021).

关键词： north annually habitat

Mori fructus aqueous extracts attenuates liver injury by inhibiting ferroptosis via the Nrf2 pathway

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Journal of Animal Science and Biotechnology 2023年第4期14卷 1418-1437页

作者： Yuanyuan Wei Chen Gao Huiru Wang Yannan Zhang Jinhua Gu Xiuying Zhang Xuhao Gong Zhihui Hao Innovation Centre of chinese veterinary medicine College of Veterinary MedicineChina Agricultural UniversityNo.2 Yuanmingyuan West RoadBeijing 100193China Key Biology Laboratory of chinese veterinary medicine Ministry of Agriculture and Rural AffairsBeijing 100193P.R.China National Center of Technology Innovation for Medicinal function of Food National Food and Strategic Reserves AdministrationBeijingChina China institute of veterinary Drug Control Beijing 100081China

Background Liver fibrosis and hepatocellular carcinogenesis secondary to liver fibrosis are serious liver diseases with no effective treatments.Mori fructus aqueous extracts(MFAEs)have served as successful treatments for many types of liver injury including fibrosis although the molecular mechanisms are unknown at present.Purpose To investigate the effect of MFAEs in alleviating acute and chronic liver injury and tried to decipher the underlying mechanism.Methods and results Mice were divided into 5 groups(n ps:contro=8)for acute(groups:control,0.3%CCl_(4),bifendate(BD),100 and 200 mg/kg MFAEs,7 d)and chronic(groul,10%CCl_(4),BD,100 and 200 mg/kg MFAEs,4 weeks)liver injury study.Each mouse was injected intraperitoneally with 10μL/g corn oil containing CCl_(4)expect the control group.HepG2 cells were used in vitro study.Eighteen communal components were identified by UPLC-LTQOrbitrap-MS.We utilized a mouse model for acute and chronic liver injury using CCl_(4)and MFAEs administration effectively blocked fibrosis and significantly inhibited inflammation in the liver.MFAEs activated the nuclear factor erythroid derived 2 like 2/heme oxygenase 1(Nrf2/HO-1)pathway and promoted the synthesis of the antioxidants glutathione(GSH),superoxidedismutase(SOD)and glutathione peroxidase(GSH-Px)that resulted in reduced levels of CCl_(4)-induced oxidative stress molecules including reactive oxygen species.These extracts administered to mice also inhibited ferroptosis in the liver by regulating the expression of Acyl-CoA synthetase long chain family member 4(ACSL4),solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),thus reducing the occurrence of liver fibrosis.Both in vivo and in vitro tests indicated that the mechanism of MFAEs protection against liver fibrosis was linked to activation of Nrf2 signaling.These effects were blocked in vitro by the addition of a specific Nrf2 inhibitor.Conclusion MFAEs inhibited oxidative stress,ferroptosis and inflammation of the liver by activating Nrf2 signal pathway an

关键词： Acute and chronic liver injury Ferroptosis Mori fructus aqueous extracts Nrf2 Oxidative stress

Application of Traditional chinese veterinary medicine in Sheep Green Breeding

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Animal Husbandry and Feed Science 2017年第5期9卷 293-297,338页

作者： Luo Chaoying Li Jinyu Wang Guibo Lanzhou institute of Husbandry & Pharmaceutics Science CAAS Lanzhou 730050 China Engineering & Technology Research Center of Traditional chinese veterinary medicine of Gansu Province Lanzhou 730050 China

Disease control and health care with traditional chinese veterinary medicine( TCVM) has attracted more and more attention in sheep green breeding. To promote healthy and smooth development of the work,the relationships between TCVM and antibiotics,and between TCVM and vaccines,were reviewed and analyzed. It was thought that TCVM and western medicine,such as antibiotics and vaccines,etc.,have their own characteristics and advantages,and should be mutually complemented rather than replaced. We should pay attention to the characteristics and advantages of the wholism concept and syndrome differentiation and treatment( diagnosis and treatment based on an overall analysis of the illness and the patient's condition) of TCVM,to develop and use TCVM health care agent or vaccine adjuvant,and their pertinence was improved according to different growth stages and physiological and pathological characteristics. Diagnosis and treatment based on an overall analysis of the illness and the population patient's condition must be attached importance to optimize the mode of administration,in order to adapt to disease prevention and control requirements in intensive and scale breeding of sheep.

关键词： Sheep green breeding Healthcare Traditional chinese veterinary medicine (TCVM) Antibiotics Vaccines

chinese Herb Formulae Inhibit the Proliferation of Human Colon Cancer SW480 Cells by Inducing Cell Apoptosis

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World Journal of Traditional chinese medicine 2023年第3期9卷 348-354页

作者： Su Fu Shao-Lin Qin Wolf-Dieter Rausch Department for Internal medicine of Traditional chinese medicine Eye Hospital China Academy of Chinese Medical SciencesBeijingChina Department for Biomedical Sciences Institute for Chemistry and BiochemistryUniversity of Veterinary Medicine ViennaViennaAustria

Objective:This study aimed to reveal the antitumor effects of chinese herbal formulae and the underlying mechanisms in treating colorectal cancer,with a focus on developing traditional chinese medicine(TCM)as a supplement and alternative therapeutic method for cancers.Materials and Methods:Human colon cancer SW480 cells were treated with three chinese herbal formulae,Bu Zhong Yi Qi Decoction,Fuzi Lizhong Decoction,and Pulsatilla Decoction at different concentrations(50–600μg/mL)for 24,36,and 48 h,respectively.Cell viability was determined using the resazurin reduction assay,and cell survival rate was evaluated using a colony formation assay.After treatment with different concentrations(50–600μg/mL)of these three formulae for 48 h,the effects of the chinese herbal formulae on cell apoptosis were investigated using Hoechst/propidium iodide(PI)staining.The positive PI-stained cells were investigated using an EnSpire multilabel plate reader and the positive Hoechst-stained cells were observed under a fluorescence microscope for morphological changes.Results:Bu Zhong Yi Qi Decoction,Fuzi Lizhong Decoction,and Pulsatilla Decoction inhibited SW480 cell proliferation in a dose-and time-dependent manner and induced cell apoptosis.Conclusion:chinese herbal formulae with a special prescription form of TCM with antitumor effects bring a new perspective in line with the principles of TCM in cancer treatment.

关键词： Apoptosis cell proliferation chinese herbal formulae colorectal cancer SW480 cells

Inosine:A broad-spectrum anti-inflammatory against SARS-CoV-2 infection-induced acute lung injury via suppressing TBK1 phosphorylation

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Journal of Pharmaceutical Analysis 2023年第1期13卷 11-23页

作者： Ningning Wang Entao Li Huifang Deng Lanxin Yue Lei Zhou Rina Su Baokun He Chengcai Lai Gaofu Li Yuwei Gao Wei Zhou Yue Gao Department of Pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing100850China Tianjin University of Traditional chinese medicine Tianjin301617China Changchun veterinary Research institute Chinese Academy of Agricultural SciencesChangchun130122China College of veterinary medicine Jilin Agricultural UniversityChangchun130022China Department of Gastroenterology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai200080China

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-induced cytokine storms constitute the primary cause of coronavirus disease 19(COVID-19)progression,severity,criticality,and death.Glucocorticoid and anti-cytokine therapies are frequently administered to treat COVID-19,but have limited clinical efficacy in severe and critical cases.Nevertheless,the weaknesses of these treatment modalities have prompted the development of anti-inflammatory therapy against this infection.We found that the broad-spectrum anti-inflammatory agent inosine downregulated proinflammatory interleukin(IL)-6,upregulated anti-inflammatory IL-10,and ameliorated acute inflammatory lung injury caused by multiple infectious agents.Inosine significantly improved survival in mice infected with SARS-CoV-2.It indirectly impeded TANK-binding kinase 1(TBK1)phosphorylation by binding stimulator of interferon genes(STING)and glycogen synthase kinase-3β(GSK3β),inhibited the activation and nuclear translocation of the downstream transcription factors interferon regulatory factor(IRF3)and nuclear factor kappa B(NF-κB),and downregulated IL-6 in the sera and lung tissues of mice infected with lipopolysaccharide(LPS),H1N1,or SARS-CoV-2.Thus,inosine administration is feasible for clinical anti-inflammatory therapy against severe and critical COVID-19.Moreover,targeting TBK1 is a promising strategy for inhibiting cytokine storms and mitigating acute inflammatory lung injury induced by SARS-CoV-2 and other infectious agents.

关键词： Cytokine stormInterleukin 6 (IL-6)InosineSARS-CoV-2TANK-binding kinase 1 (TBK1)

Nucleolin interacts with the rabbit hemorrhagic disease virus replicase RdRp, nonstructural proteins p16 and p23, playing a role in virus replication

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Virologica Sinica 2022年第1期37卷 48-59页

作者： Jie Zhu Qiuhong Miao Hongyuan Guo Aoxing Tang Dandan Dong Jingyu Tang Fang Wang Guangzhi Tong Guangqing Liu Shanghai veterinary Research institute Chinese Academy of Agricultural SciencesShanghai200241China Laboratory of Virology Wageningen University and ResearchWageningen6708 PBthe Netherlands institute of veterinary medicine Jiangsu Academy of Agricultural SciencesNanjing210014China

Rabbit hemorrhagic disease virus(RHDV)is a member of the Caliciviridae family and cannot be propagated in vitro,which has impeded the progress of investigating its replication mechanism.Construction of an RHDV replicon system has recently provided a platform for exploring RHDV replication in host cells.Here,aided by this replicon system and using two-step affinity purification,we purified the RHDV replicase and identified its associated host factors.We identified rabbit nucleolin(NCL)as a physical link,which mediating the interaction between other RNA-dependent RNA polymerase(Rd Rp)-related host proteins and the viral replicase Rd Rp.We found that the overexpression or knockdown of NCL significantly increased or severely impaired RHDV replication in RK-13 cells,respectively.NCL was identified to directly interact with RHDV Rd Rp,p16,and p23.Furthermore,NCL knockdown severely impaired the binding of Rd Rp to Rd Rp-related host factors.Collectively,these results indicate that the host protein NCL is essential for RHDV replication and acts as a physical link between viral replicase and host proteins.

关键词： Rabbit hemorrhagic disease virus(RHDV) Nucleolin Virus replication RNA-dependent RNA polymerase(RdRp)

Genome degradation promotes Salmonella pathoadaptation by remodeling fimbriae-mediated proinflammatory response

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National Science Review 2023年第10期10卷 32-43页

作者： Xiao Zhou Xiamei Kang Jiaqi Chen Yan Song Chenghao Jia Lin Teng Yanting Tang Zhijie Jiang Xianqi Peng Xiaoxi Tao Yiwei Xu Linlin Huang Xuebin Xu Yaohui Xu Tengfei Zhang Shenye Yu Jiansen Gong Shaohui Wang Yuqing Liu Guoqiang Zhu Corinna Kehrenberg Fran?ois-Xavier Weill Paul Barrow Yan Li Guoping Zhao Min Yue Shandong Key Laboratory of Animal Disease Control and Breeding Institute of Animal Science and Veterinary MedicineShandong Academy of Agricultural Sciences College of veterinary medicine Yangzhou University institute for veterinary Food Science Faculty of Veterinary MedicineJustus-Liebig University Giessen Institut Pasteur Université Paris Cité Unité des bactéries pathogènes entériques School of veterinary medicine University of Surrey School of Life Science Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences CAS Key Laboratory of Synthetic Biology Institute of Plant Physiology and EcologyShanghai Institutes for Biological SciencesChinese Academy of Sciences Department of Microbiology and Microbial Engineering School of Life SciencesFudan University State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesThe First Affiliated Hospital College of Medicine Zhejiang University Zhejiang Provincial Key Laboratory of Preventive veterinary medicine institute of Preventive veterinary Sciences and Department of veterinary medicine Zhejiang University College of Animal Sciences Ningbo Academy of Agricultural Sciences Hainan institute of Zhejiang University Department of Microbiology Laboratory Shanghai Municipal Center for Disease Control and Prevention College of veterinary medicine Henan University of Animal Husbandry and Economy Key Laboratory of Prevention and Control Agents for Animal Bacteriosis Institute of Animal Husbandry and Veterinary Hubei Academy of Agricultural Sciences Division of Bacterial Diseases State Key Laboratory of Veterinary BiotechnologyHarbin Veterinary Research InstituteChinese Academy of Agricultural Sciences Poultry institute Chinese Academy of Agricultural Sciences Department of Animal Public Health Shanghai Veterinary Research Institute Chinese Academy of Agricultural Sciences

Understanding changes in pathogen behavior(e.***.increased virulence,a shift in transmission channel) is critical for the public health management of emerging infectious diseases.Genome degradation via gene depletion or inactivation is recognized as a pathoadaptive feature of the pathogen evolving with the host.However,little is known about the exact role of genome degradation in affecting pathogenic behavior,and the underlying molecular detail has yet to be examined.Using large-scale global avian-restricted Salmonella genomes spanning more than a century,we projected the genetic diversity of Salmonella Pullorum(bvSP)by showing increasingly antimicrobial-resistant ST92 prevalent in chinese flocks.The phylogenomic analysis identified three lineages in bvSP,with an enhancement of virulence in the two recently emerged lineages(L2/L3),as evidenced in chicken and embryo infection assays.Notably,the ancestor L1 lineage resembles the Salmonella serovars with higher metabolic flexibilities and more robust environmental tolerance,indicating stepwise evolutionary trajectories towards avian-restricted lineages.Pan-genome analysis pinpointed fimbrial degradation from a virulent lineage.The later engineeredfim-deletion mutant,and all other five fimbrial systems,revealed behavior switching that restricted horizontal fecal-oral transmission but boosted virulence in chicks.By depleting fimbrial appendages,bvSP established persistent replication with less proinflammation in chick macrophages and adopted vertical transovarial transmission,accompanied by ever-increasing intensification in the poultry industry.Together,we uncovered a previously unseen paradigm for remodeling bacterial surface appendages that supplements virulence-enhanced evolution with increased vertical transmission.

关键词： Salmonella host adaptation pathogenic evolution virulence evolution vertical transmission fimbrial adhesin

The outbreak of rabbit hemorrhagic virus type 2 in the interior of China may be related to imported semen

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Virologica Sinica 2022年第4期37卷 623-626页

作者： Ruibin Qi Chunchun Meng Jie Zhu Hang Li Qiuhong Miao Jingyu Tang Aoxing Tang Hongyuan Guo Chuncao Liu Chuanfeng Li Zongyan Chen Fang Wang Qinwen Zhang Guangqing Liu Innovation Team of Small Animal Infectious Disease Shanghai Veterinary Research InstituteChinese Academy of Agricultural SciencesShanghai200241China institute of veterinary medicine Jiangsu Academy of Agricultural SciencesNanjing210014China veterinary medicine Department of Agricultural and Animal College Qinghai UniversityXining810016China

Dear Editor,Rabbit hemorrhagic disease(RHD)is a fatal infectious disease that primarily affects adult rabbits and causes great economic losses in the rabbit industry(Mitro and Krauss,1993).The causative pathogen is rabbit hemorrhagic disease virus(RHDV),which belongs to the genus Lagovirus and the family Calicivirus(Moussa et al.,1992).In 1984,RHDV was first documented in China.

关键词： rabbit Rabbit interior