SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries,how-ever,the underlying mechanism,in particular immune responses in different organs,remains elusive.In this study,comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed.Compared to normal controls,SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs,with drastic transcriptomic changes in cerebral cortex and right ventricle.Intriguingly,cerebral cortex exhibited a hyperinflammatory state evidenced by sig-nificant upregulation of inflammation response-related genes.Meanwhile,expressions of coagulation,angio-genesis and fibrosis factors were also up-regulated in cerebral cortex.Based on our findings,neuropilin 1(NRP1),a receptor of SARS-CoV-2,was significantly elevated in cerebral cortex post infection,accompanied by active immune response releasing inflammatory factors and signal transmission among tissues,which enhanced infection of the central nervous system(CNS)in a positive feedback way,leading to viral encephalitis.Overall,our study depicts a multi-tissue/organ tran-scriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2,and provides important insights into the mechanistic basis for COVID-19-asso-ciated clinical complications.

Chun-Chun Gao;Man Li;Wei Deng;Chun-Hui Ma;Yu-Sheng Chen;Yong-Qiao Sun;Tingfu Du;Qian-Lan Liu;Wen-Jie Li;Bing Zhang;Lihong Sun;Si-Meng Liu;Fengli Li;Feifei Qi;Yajin Qu;Xinyang Ge;Jiangning Liu;Peng Wang;Yamei Niu;Zhiyong Liang;Yonig-Liang Zhao;Bo Huang;Xiao-Zhong Peng;Ying Yang;Chuan Qin;Wei-Min Tong;Yun-Gui Yang

CAS Key Laboratory of Genomic and Precision Medicine,Collaborative Innovation Center of Genetics and Development,College of Future Technology,Beijing Institute of Genomics,Chinese Academy of Sciences,Beijing 100101,China;China National Center for Bioinformation,Beijing 100101,China;Sino-Danish College,University of Chinese Academy of Sciences,Beijing 101408,China;Department of Pathology,Beijing Ditan Hospital,Capital Medical University,Beijing 100000,China;Department of Pathology,Institute of Basic Medical Sciences,Molecular Pathology Research Center,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100005,China;NHC Key Laboratory of Human Disease Comparative Medicine,Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases;Institute of Stem Cell and Regeneration,Chinese Academy of Sciences,Beijing 100101,China;Institute of Medical Biology,Chinese Academy of Medical Sciences and Peking Union Medical College,Kunming 650031,China;Center for Experimental Animal Research,Institute of Basic Medical Sciences Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100005,China;Department of Pathology,Peking Union Medical College Hospital,Molecular Pathology Research Center,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100005,China;Department of Immunology&National Key Laboratory of Medical Molecular Biology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100005,China;Clinical Immunology Center,Chinese Academy of Medical Sciences,Beijing 100005,China;Department of Biochemistry&Molecular Biology,Tongji Medical College,Huazhong University of Science&Technology,Wuhan 430030,China;Institute of Laboratory Animal Science,Chinese Academy of Medical Sciences and Comparative Medicine Center,Peking Union Medical College,Beijing 100021,China

蛋白质与细胞

[1]Chun-Chun Gao;Man Li;Wei Deng;Chun-Hui Ma;Yu-Sheng Chen;Yong-Qiao Sun;Tingfu Du;Qian-Lan Liu;Wen-Jie Li;Bing Zhang;Lihong Sun;Si-Meng Liu;Fengli Li;Feifei Qi;Yajin Qu;Xinyang Ge;Jiangning Liu;Peng Wang;Yamei Niu;Zhiyong Liang;Yonig-Liang Zhao;Bo Huang;Xiao-Zhong Peng;Ying Yang;Chuan Qin;Wei-Min Tong;Yun-Gui Yang-.Differential transcriptomic landscapes of multiple organs from SARS-CoV-2 early infected rhesus macaques)[J].蛋白质与细胞,2022(12):920-939

hyperinflammatory,scriptomic

Differential,transcriptomic,landscapes,multiple,organs,from,SARS,CoV,early,infected,rhesus,macaques,infection,causes,complicated,clinical,manifestations,variable,injuries,how,ever,underlying,mechanism,particular,immune,responses,different,remains,elusive,this,study,comprehensive,alterations,tissues,were,analyzed,Compared,normal,controls,resulted,dysregulation,involving,diverse,functions,various,examined,drastic,changes,cerebral,cortex,right,ventricle,Intriguingly,exhibited,state,evidenced,by,upregulation,inflammation,related,Meanwhile,expressions,coagulation,angio,genesis,fibrosis,factors,also,regulated,Based,our,findings,neuropilin,NRP1,receptor,was,significantly,elevated,post,accompanied,active,releasing,signal,transmission,among,which,enhanced,central,nervous,system,CNS,positive,feedback,way,leading,viral,encephalitis,Overall,depicts,provides,important,insights,into,mechanistic,basis,asso,ciated,complications

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