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Establishment of an indirect immunofluorescence assay for the detection of African swine fever virus antibodies

Journal of Integrative Agriculture 2024年第1期23卷 228-238页

作者： Wan Wang Zhenjiang Zhang Weldu Tesfagaber Jiwen Zhang Fang Li Encheng Sun Lijie Tang Zhigao Bu Yuanmao Zhu Dongming Zhao State Key Laboratory for animal Disease control and Prevention National African Swine Fever Para-reference LaboratoryNational High Containment Facilities for Animal Diseases Control and PreventionHarbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China College of Veterinary medicine Northeast Agricultural UniversityHarbin 150069China

African swine fever(ASF)continues to cause enormous economic loss to the global pig *** there is no safe and effective vaccine,accurate and timely diagnosis of ASF is essential to implement control *** immunofluorescence assay(IFA)is a gold standard serological method recommended by the World Organization for animal Health(WOAH).In this study,we used primary fetal kidney cells to establish a wild boar cell line(BK2258)that supported the efficient replication of ASF virus(ASFV)SD/DY-I/21 and showed visible cytopathic effect(CPE).Moreover,using BK2258,we established a sensitive and specific IFA for ASFV antibody *** standardize and evaluate the performance of this assay,we used serum samples from pigs infected with the low virulent genotype I SD/DY-I/21 and genotype II HLJ/HRB1/20,and immunized with the vaccine candidate HLJ/18-7GD,field samples,and negative serum *** IFA reacted with the ASFV-positive sera and displayed bright fluorescence *** was no non-specific green fluorescence due to cellular senescence or other cell damage-causing *** to a commercial indirect enzyme-linked immunosorbent assay(iELISA),ASFV antibodies were detected 1–4 days earlier using our *** detection limits of the IFA and iELISA for the same ASFV-antibody positive serum samples were 1:25,600 and 1:6,400,respectively,indicating that the IFA is more sensitive than *** newly established IFA was highly specific and did not cross-react with sera positive for six other important porcine pathogens(i.e.,Classical swine fever virus(CSFV),Porcine reproductive and respiratory syndrome virus(PRRSV),Porcme circovirus type 2(PCV2),Pseudorabies virus(PRV),Foot-and-Mouth disease virus type O(FMDV/O),and Porcine epidemic diarrhea virus(PEDV)).This study thus provides a sensitive,specific,and reliable detection method that is suitable for the serological diagnosis of ASF.

关键词： African swine fever antibody IFA serological method

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Multi-omic Analyses Shed Light on The Genetic control of High-altitude Adaptation in Sheep

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Genomics, Proteomics & Bioinformatics 2024年第2期22卷 43-56页

作者： Chao Li Bingchun Chen Suo Langda Peng Pu Xiaojia Zhu Shiwei Zhou Peter Kalds Ke Zhang Meenu Bhati Alexander Leonard Shuhong Huang Ran Li Awang Cuoji Xiran Wang Haolin Zhu Yujiang Wu Renqin Cuomu Ba Gui Ming Li Yutao Wang Yan Li Wenwen Fang Ting Jia Tianchun Pu Xiangyu Pan Yudong Cai Chong He Liming Wang Yu Jiang Jian-Lin Han Yulin Chen Ping Zhou Hubert Pausch Xiaolong Wang International Joint Agriculture Research Center for animal Bio-Breeding Ministry of Agriculture and Rural Affairs/Key Laboratory of Animal GeneticsBreeding and Reproduction of Shaanxi ProvinceCollege of Animal Science and TechnologyNorthwest A&F UniversityYangling 712100China animal Genomics ETH ZürichZürich 8092Switzerland institute of animal Science Tibet Academy of Agricultural and Animal Husbandry SciencesLhasa 850009China School of Biological and Pharmaceutical Engineering Lanzhou Jiaotong UniversityLanzhou 730070China College of Life Sciences Shaanxi Normal UniversityXi’an 710119China Zoology and Evolutionary Biology Department of BiologyUniversity of Konstanz78457 KonstanzGermany College of Life and Geographic Sciences Kashi UniversityKashi 844000China Beijing Key Laboratory of Captive Wildlife Technologies Beijing ZooBeijing 100044China Department of Medical Research Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China Key Laboratory of Agricultural Internet of Things Ministry of Agriculture and Rural Affairs/Shaanxi Key Laboratory of Agricultural Information Perception and Intelligent ServiceCollege of Information EngineeringNorthwest A&F UniversityYangling 712100China institute of animal Husbandry and Veterinary medicine Xinjiang Academy of Agricultural and Reclamation SciencesShihezi 832000China State Key Laboratory of Sheep Genetic Improvement and Healthy Production Xinjiang Academy of Agricultural and Reclamation SciencesShihezi 832000China CAAS-ILRI Joint Laboratory on Livestock and forage Genetic Resources Institute of Animal ScienceChinese Academy of Agricultural SciencesBeijing 100193China Livestock Genetics Program International Livestock Research InstituteNairobi 00100Kenya

Sheep were domesticated in the Fertile Crescent and then spread globally,where they have been encountering various environmental *** Tibetan sheep has adapted to high altitudes on the Qinghai-Tibet Plateau over the past 3000 *** explore genomic variants associated with high-altitude adaptation in Tibetan sheep,we analyzed Illumina short-reads of 994 whole genomes representing∼60 sheep breeds/populations at varied altitudes,PacBio High fidelity(HiFi)reads of 13 breeds,and 96 transcriptomes from 12 sheep *** testing between the inhabited altitudes and 34,298,967 variants was conducted to investigate the genetic architecture of altitude *** accurate HiFi reads were used to complement the current ovine reference assembly at the most significantly associatedβ-globin locus and to validate the presence of two haplotypes A and B among 13 sheep *** haplotype A carried two homologous gene clusters:(1)HBE1,HBE2,HBB-like,and HBBC,and(2)HBE1-like,HBE2-like,HBB-like,and HBB;while the haplotype B lacked the first *** high-altitude sheep showed highly frequent or nearly fixed haplotype A,while the low-altitude sheep dominated by haplotype *** further demonstrated that sheep with haplotype A had an increased hemoglobin–O2 affinity compared with those carrying haplotype *** highly associated genomic region contained the EGLN1 gene which showed varied expression between high-altitude and low-altitude *** results provide evidence that the rapid adaptive evolution of advantageous alleles play an important role in facilitating the environmental adaptation of Tibetan sheep.

关键词： Environmental adaptation High altitude Hypoxia Selection signature Sheep

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Production Technology and Application of Slow-Release Non-protein Nitrogen Extruded Feed Additive

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animal Husbandry and Feed Science 2011年第3期3卷 7-8,12页

作者： XIE Hong-wei SUN Dong-bo LIU Bo-chen DING Lan-feng BAO Yu-qing SHI Jian-chun control institute of animal medicine and forage of Yitong Manchu Autonomous County of Jilin Province Yitong Manchu 130700 China College of animal Science & Veterinary medicine Heilongjiang Bayi Agricultural University Daqing 163319 China College for Nationalities Harbin 150081 China heilongjiang control institute of animal medicine and forage Harbin 150081 China

Slow-release non-protein nitrogen feed has a large market demand. It has a long research history, but its production technology needs further improvement in order to realize the industrial production of slow-release non-protein nitrogen extruded feed. By designing the best formula and using chelating and emulsifying process, the slow-release non-protein nitrogen extruded feed additives were produced. This product increases milk yield and improves milk quality, thus increasing economic efficiency.

关键词： Slow release Non-protein nitrogen Feed additives Ruminants

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利用金属有机框架抑制PI3K/AKT/mTOR信号传导通路以克服放化疗中的多重耐药性

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Science China Materials 2024年第5期67卷 1631-1645页

作者：宋春雨关雪谢昌明姜珊洪智文吴琼曲国蕃马腾闯崔亚利 Department of Orthopedics Harbin Medical University Cancer HospitalHarbin150081China animal Laboratory Center The Second Affiliated Hospital of Harbin Medical UniversityHarbin150081China Department of Thyroid Surgery Key Laboratory of Hepatosplenic SurgeryMinistry of EducationThe First Affiliated Hospital of Harbin Medical UniversityHarbin150007China Department of Nuclear medicine Harbin Medical University Cancer HospitalHarbin150081China Laboratory of controllable Preparation and Application of Nanomaterials Key Laboratory of CryogenicsTechnical Institute of Physics and ChemistryChinese Academy of SciencesBeijing100190China

肿瘤微环境中的血管生成是肿瘤细胞对放化疗不敏感的主要原因.在本项研究中,我们设计了一种微环境响应型的纳米颗粒,利用ZrMOF的分解产物抑制肿瘤细胞中的PI3K/AKT/mTOR/VEGF通路,从而克服A549R细胞对顺铂的耐药性.我们将顺铂包裹在Zr-... 详细信息

肿瘤微环境中的血管生成是肿瘤细胞对放化疗不敏感的主要原因.在本项研究中,我们设计了一种微环境响应型的纳米颗粒,利用ZrMOF的分解产物抑制肿瘤细胞中的PI3K/AKT/mTOR/VEGF通路,从而克服A549R细胞对顺铂的耐药性.我们将顺铂包裹在Zr-MOF中,并在表面修饰BSA,形成了CDDP@Zr-MOF-BSA纳米复合体,该复合体在肿瘤微环境中有良好的响应性,有助于在肿瘤区域蓄积,展现出卓越的血管生成抑制能力,并能明显降低药物的外排.此外,CDDP@Zr-MOFBSA能显著抑制多药耐药相关蛋白1(MRP1)的表达,从而逆转A549R细胞的耐药性.总体而言,CDDP@Zr-MOF-BSA对A549R有细胞毒性,能抑制肿瘤微环境中的血管生成,最终有效提高顺铂耐药肿瘤的治疗效果.CDDP@Zr-MOF-BSA为放化疗治疗耐药肿瘤提供了一种多功能协同的方法.

关键词： angiogenesis multidrug resistance radiotherapy Zr-MOF microenvironment

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Nano-selenium alleviates cadmium-induced cerebellar injury by activating metal regulatory transcription factor 1 mediated metal response

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animal Nutrition 2022年第4期11卷 402-412页

作者： Shao-Shuai Bi Milton Talukder Hai-Tao Jin Mei-Wei Lv Jing Ge Cong Zhang Jin-Long Li College of Veterinary medicine Northeast Agricultural UniversityHarbin 150030China College of Biotechnology and Pharmaceutical Engineering of West Anhui University Lu’an 237012China Department of Physiology and Pharmacology Faculty of Animal Science and Veterinary MedicinePatuakhali Science and Technology UniversityBarishal8210Bangladesh Quality and Safety institute of Agricultural Products Heilongjiang Academy of Agricultural SciencesHarbin 150010China College of Veterinary medicine Henan Agricultural UniversityZhengzhou 450002China Key Laboratory of the Provincial Education Department of heilongjiang for Common animal Disease Prevention and Treatment Northeast Agricultural UniversityHarbin 150030China heilongjiang Key Laboratory for Laboratory animals and Comparative medicine Northeast Agricultural UniversityHarbin 150030China

This study aims to investigate the role of metal regulatory transcription factor 1(MTF1)-mediated metal response in cadmium(Cd)-induced cerebellar injury,and to evaluate the antagonistic effects of nanoselenium(Nano-Se)against Cd toxicity.A total of 80 chicks(1 d old,male,Hy-Line Variety White)were randomly allocated to 4 treatment groups for 3 months:the control group(fed with a basic diet,n=20),the Nano-Se group(basic diet with 1 mg/kg nano-Se 1 mg/kg Nano-Se in basic diet,n=20),the NanoSe+Cd group(basic diet with 1 mg/kg Nano-Se and 140 mg/kg Cd Cl_(2),n=20)and the Cd group(basic diet with 140 mg/kg Cd Cl_(2),n=20).The results of the experiment showed that the Purkinje cells were significantly decreased with their degradation and indistinct nucleoli after Cd ***,exposure to Cd caused a significant accumulation of Cd and ***,the contents of Se,iron,and zinc were decreased,thereby disturbing the metal homeostasis in the *** Cd exposure also resulted in high levels of malondialdehyde(MDA)and down regulation of selenoprotein ***,the expressions of MTF1,metallothionein 1(MT1),MT2,zinc transporter 3(ZNT3),ZNT5,ZNT10,zrt,irt-like protein 8(ZIP8),ZIP10,transferrin(TF),ferroportin 1(FPN1),ATPase copper transporting beta(ATP7B),and copper uptake protein 1(CTR1)were inhibited by Cd ***,all these changes were significantly alleviated by the supplementation of *** study proved that Cd could disorder metal homeostasis and induce oxidative stress,whereas Nano-Se could relieve all these negative effects caused by Cd via activating the MTF1-mediated metal response in the cerebellum of chicken.

关键词： Nano-selenium Cadmium Selenoprotein transcriptome MTF1-mediated metal response Cerebellar injury

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Green tea polyphenols supplementation alters immunometabolism and oxidative stress in dairy cows with hyperketonemia

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animal Nutrition 2021年第1期7卷 206-215页

作者： Yanfen Ma Ying Feng Liwen Song Muyang Li Hongyu Dai Hua Bao Guijie Zhang Lei Zhao Chunhua Zhang Jing Yi Yusheng Liang School of Agriculture Ningxia UniversityYinchuan 750021China institute of animal Nutrition and Feed Inner Mongolia Academy of Agriculture and Animal Husbandry SciencesHohhot 010031China College of Food Engineering&Biotechnology Tianjin University of Science&TechnologyTianjin 300457China College of animal Science and Veterinary medicine Heilongjiang Bayi Agricultural UniversityDaqing 163316China College of Veterinary medicine Nanjing Agricultural UniversityNanjing 210095China Department of animal Sciences and Division of Nutritional Sciences University of IllinoisUrbana 61801USA

Peripartal cows often experience negative energy balance,and are therefore prone to suffering from metabolic diseases such as hyperketonemia,which causes financial losses in dairy *** study aimed to investigate the effect of green tea polyphenol(GTP)supplementation during the periparturient period on production performance,oxidative stress and immunometabolism in dairy cows with *** hundred Holstein cows were assigned to GTP(0.2 g/kg DM;n=50)or control(without GTP;n=50)group based on body weight,previous milk yield,and parity on d 15 before expected ***,10 cows with hyperketonemia were selected from each group,according to bloodβ-hydroxybutyric acid(BHBA)concentration between 1.2 and 2.9 mmol/L from 2 to 3 d *** cows were fed a close-up diet and a lactation diet with or without GTP supply from 15 d prepartum until 30 d *** and blood samples were obtained from 20 cows selected with hyperketonemia on 10,20,and 30 d *** with control cows,greater milk yield and lower somatic cell count were observed in GTP *** GTP group had lower concentrations of BHBA,free fatty acids,cholesterol,triglyceride,reactive oxygen species,malondialdehyde,and hydrogen peroxide,greater concentrations of glucose,lower activities of aspartate aminotransferase,alanine aminotransferase,and glutamyl transpeptidase,alongside greater ac-tivities of superoxide dismutase,glutathione peroxidase,and total antioxidant ***,GTP supplementation up-regulated concentrations of interleukin-6 and interleukin-10,but down-regulated concentrations of tumor necrosis factor-α,interleukin-1β,interleukin-2,interleukin-8,and interferon-γin *** concentrations of plasma immunoglobulin G were also detected in the GTP ***,the data suggested that GTP supplementation from 15 d prepartum to 30 d postpartum improved the milk yield and health status in cows with hvoerketonemia during early lactation.

关键词： Green tea polyphenol Hyperketonemia Peripartal period Dairy cow

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IP10, KC and M-CSF Are Remarkably Increased in the Brains from the Various Strains of Experimental Mice Infected with Different Scrapie Agents

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Virologica Sinica 2020年第5期35卷 614-625页

作者： Jia Chen Cao Chen Chao Hu Lian Liu Ying Xia Lin Wang Wei Yang Hai-Yan Wu Wei Zhou Kang Xiao Qi Shi Yuezhang Wu Zhi-Bao Chen Xiao-Ping Dong College of animal Science and Veterinary medicine Heilongjiang Bayi Agricultural UniversityDaqing 163000China State Key Laboratory of Infectious Disease Prevention and control NHC Key Laboratory of Medical Virology and Viral DiseasesNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 100000China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases Zhejiang UniversityHangzhou 310000China Center for Global Public Health Chinese Center for Disease Control and PreventionBeijing 100000China Center for Biosafety Mega-Science Chinese Academy of SciencesWuhan 430000China China Academy of Chinese Medical Sciences Beijing 100000China College of Life Science and Technology Heilongjiang Bayi Agricultural UniversityDaqing 163000China

Activation of inflammatory cells and upregulations of a number of cytokines in the central nervous system(CNS)of patients with prion diseases are frequently *** evaluate the potential changes of some brain cytokines that were rarely addressed during prion infection,the levels of 17 different cytokines in the brain homogenates of mice infected with different scrapie mouse-adapted agents were firstly screened with Luminex *** upregulations of interferon gamma-induced protein 10(IP10),keratinocyte chemoattractant(KC)and macrophage colony stimulating factor(M-CSF)were frequently detected in the brain lysates of many strains of scrapie infected *** upregulations of those three cytokines in the brains of scrapie infected mice were further validated by the individual specific ELISA and immunohistochemical *** specific mRNAs of IP10,M-CSF and KC in the brains of scrapie infected mice were also detected by the individual specific qRT-PCRs and IP10-specific digital *** analyses of the brain samples collected at different time points post infection revealed the time-dependent increases of those three cytokines,particularly IP10 during the incubation period of scrapie *** addition,we also found that the levels of IP10 in cerebral spinalfluid(CSF)of 45 sporadic Creutzfeldt–Jakob disease(sCJD)patients were slightly but significantly higher than those of the cases who were excluded the diagnosis of prion *** data give us a better understanding of inflammatory reaction during prion infection and progression of prion disease.

关键词： Prion Cytokines Interferon gamma-induced protein 10(IP10) Keratinocyte chemoattractant(KC) Macrophage colony stimulating factor(M-CSF)

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Nuciferine protects against high-fat diet-induced hepatic steatosis and insulin resistance via activating TFEB-mediated autophagy——lysosomal pathway

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Acta Pharmaceutica Sinica B 2022年第6期12卷 2869-2886页

作者： Xiliang Du Chiara Di Malta Zhiyuan Fang Taiyu Shen Xiaodi Niu Meng Chen Bo Jin Hao Yu Lin Lei Wenwen Gao Yuxiang Song Zhe Wang Chuang Xu Zhijun Cao Guowen Liu Xinwei Li Key Laboratory of Zoonosis Ministry of EducationCollege of Veterinary MedicineJilin UniversityChangchun 130062China Telethon institute of Genetics and medicine(TIGEM)Via Campi Flegrei 34 PozzuoliNA 80078Italy Medical Genetics Unit Department of Medical and Translational ScienceFederico Ⅱ UniversityNaples 80131Italy College of Food Science and Engineering Jilin UniversityChangchun 130062China College of animal Science and Veterinary medicine Heilongjiang Bayi Agricultural UniversityDaqing 163319China State Key Laboratory of animal Nutrition Beijing Engineering Technology Research Center of Raw Milk Quality and Safety ControlCollege of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China

Nonalcoholic fatty liver disease(NAFLD) is characterized by hepatic steatosis and insulin resistance and there are currently no approved drugs for its *** of mTOR complex1(mTORCl) and subsequent impairment of the transcription factor EB(TFEB)-mediated autophagy-lysosomal pathway(ALP) are implicated in the development of ***,agents that augment hepatic TFEB transcriptional activity may have therapeutic potential against *** objective of this study was to investigate the effects of nuciferine,a major active component from lotus leaf,on NAFLD and its underlying mechanism of *** we show that nuciferine activated ALP and alleviated steatosis,insulin resistance in the livers of NAFLD mice and palmitic acid-challenged hepatocytes in a TFEB-dependent *** investigation revealed that nuciferine interacts with the Ragulator subunit hepatitis B X-interacting protein and impairs the interaction of the Ragulator complex with Rag GTPases,thereby suppressing lysosomal localization and activity of mTORC1,which activates TFEB-mediated ALP and further ameliorates hepatic steatosis and insulin *** present results indicate that nuciferine may be a potential agent for treating NAFLD and that regulation of the mTORCl-TFEB-ALP axis could represent a novel pharmacological strategy to combat NAFLD.

关键词： Autophagy Fatty liver Lotus leaf Lysosome MiT/TFE mTORC1 Ragulator TFEB

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The dichotomous and incomplete adaptive immunity in COVID-19 patients with different disease severity

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Signal Transduction and Targeted Therapy 2021年第4期6卷 1292-1301页

作者： Leiqiong Gao Jing Zhou Sen Yang Lisha Wang Xiangyu Chen Yang Yang Ren Li Zhiwei Pan Jing Zhao Zhirong Li Qizhao Huang Jianfang Tang Li Hu Pinghuang Liu Guozhong Zhang Yaokai Chen Lilin Ye institute of Immunology Third Military Medical UniversityChongqingChina Chongqing Public Health Medical Center ChongqingChina State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbinHeilongjiangChina College of Veterinary medicine Northeast Agricultural UniversityHarbinHeilongjiangChina Key Laboratory of animal Epidemiology of the Ministry of Agriculture College of Veterinary MedicineChina Agricultural UniversityBeijingChina Cancer Center The General Hospital of Western Theater CommandChengduSichuanChina Comparative Immunology Research Center College of Veterinary MedicineChina Agricultural UniversityBeijingChina

The adaptive immunity that protects patients from coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is not well *** particular,the asymptomatic patients have been found to induce weak and transient SARS-CoV-2 antibody responses,but the underlying mechanisms remain unknown;meanwhile,the protective immunity that guide the recovery of these asymptomatic patients is ***,we characterized SARS-CoV-2-specific B-cell and T-cell responses in 10 asymptomatic patients and 64 patients with other disease severity(mild,n=10,moderate,n=32,severe,n=12)and found that asymptomatic or mild symptomatic patients failed to mount virus-specific germinal center(GC)B cell responses that result in robust and prolonged humoral immunity,assessed by GC response indicators including follicular helper T(TFH)cell and memory B cell responses as well as serum CXCL13 ***,these patients mounted potent virus-specific TH1 and CD8+T cell *** sharp contrast,patients of moderate or severe disease induced vigorous virus-specific GC B cell responses and associated TFH responses;however,the virus-specific TH1 and CD8+T cells were minimally induced in these *** results,therefore,uncovered the protective immunity in asymptomatic patients and also revealed the strikingly dichotomous and incomplete humoral and cellular immune responses in COVID-19 patients with different disease severity,providing important insights into rational design of effective COVID-19 vaccines.

关键词： immunity patients severity

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Replication, pathogenicity, and transmission of SARS-CoV-2 in minks

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National Science Review 2021年第3期8卷 21-28页

作者： Lei Shuai Gongxun Zhong Quan Yuan Zhiyuan Wen Chong Wang Xijun He Renqiang Liu Jinliang Wang Qinjian Zhao Yuxiu Liu Ningning Huo Junhua Deng Jingjing Bai Hongchao Wu Yuntao Guan Jianzhong Shi Kegong Tian Ningshao Xia Hualan Chen Zhigao Bu State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research Institute Chinese Academy of Agricultural Sciences National High Containment Laboratory for animal Diseases control and Prevention State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics National Institute of Diagnostics and Vaccine Development in Infectious DiseasesSchool of Public Health Xiamen University National Research Center for Veterinary medicine

Minks are raised in many countries and have transmitted severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) to ***,the biologic properties of SARS-CoV-2 in minks are largely ***,we investigated and found that SARS-CoV-2 replicates efficiently in both the upper and lower respiratory tracts,and transmits efficiently in minks via respiratory droplets;pulmonary lesions caused by SARS-CoV-2 in minks are similar to those seen in humans with *** further found that a spike protein-based subunit vaccine largely prevented SARS-CoV-2 replication and lung damage caused by SARS-CoV-2 infection in *** study indicates that minks are a useful animal model for evaluating the efficacy of drugs or vaccines against COVID-19 and that vaccination is a potential strategy to prevent minks from transmitting SARS-CoV-2.

关键词： SARS-CoV-2 mink replication pathogenicity transmission animal model

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