Differential Transcriptomic Landscapes of SARS-CoV-2 Variants in Multiple Organs from Infected Rhesus Macaques  

作　　者：Tingfu Du Chunchun Gao Shuaiyao Lu Qianlan Liu Yun Yang Wenhai Yu Wenjie Li Yong Qiao Sun Cong Tang Junbin Wang Jiahong Gao Yong Zhang Fangyu Luo Ying Yang Yun-Gui Yang Xiaozhong Peng 

机构地区：[1]National Kunming High-level Biosafety Primate Research Center,Institute of Medical Biology,Chinese Academy of Medical Sciences and Peking Union Medical College,Kunming 650118,China [2]State Key Laboratory of Medical Molecular Biology,Department of Molecular Biology and Biochemistry,Institute of Basic Medical Sciences,Medical Primate Research Center,Neuroscience Center,Chinese Academy of Medical Sciences,School of Basic Medicine,Peking Union Medical College,Beijing 100005,China [3]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 and China National Center for Bioinformation,Beijing 100101,China [4]Sino-Danish College,University of Chinese Academy of Sciences,Beijing 100049,China [5]Institute of Stem Cell and Regeneration,Chinese Academy of Sciences,Beijing 100101,China [6]Institute of Laboratory Animal Science,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China

出　　处：《Genomics, Proteomics & Bioinformatics》2023年第5期1014-1029,共16页基因组蛋白质组与生物信息学报（英文版）

基　　金：supported by the National Key R&D Program of China(Grant No.2021YFC0863300);the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB0490000);the CAMS Innovation Fund for Medical Sciences(Grant No.2021-I2M-1-024);the STI2030-Major Projects(Grant No.2021ZD0200900);the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(Grant No.82221004);the National Natural Science Foundation of China(Grant Nos.32121001,32200460,and 32200460);the K.C.Wong Education Foundation(Grant No.GJTD-2019-08);the Shanghai Municipal Science and Technology Major Project,China(Grant No.2017SHZDZX01);the China National Postdoctoral Program for Innovative Talents(Grant No.BX2021291).

摘　　要：Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)caused the persistent coronavirus disease 2019(COVID-19)pandemic,which has resulted in millions of deaths worldwide and brought an enormous public health and global economic burden.The recurring global wave of infections has been exacerbated by growing variants of SARS-CoV-2.In this study,the virological characteristics of the original SARS-CoV-2 strain and its variants of concern(VOCs;including Alpha,Beta,and Delta)in vitro,as well as differential transcriptomic landscapes in multiple organs(lung,right ventricle,blood,cerebral cortex,and cerebellum)from the infected rhesus macaques,were elucidated.The original strain of SARS-CoV-2 caused a stronger innate immune response in host cells,and its VOCs markedly increased the levels of subgenomic RNAs,such as N,Orf9b,Orf6,and Orf7ab,which are known as the innate immune antagonists and the inhibitors of antiviral factors.Intriguingly,the original SARS-CoV-2 strain and Alpha variant induced larger alteration of RNA abundance in tissues of rhesus monkeys than Beta and Delta variants did.Moreover,a hyperinflammatory state and active immune response were shown in the right ventricles of rhesus monkeys by the up-regulation of inflammation-and immune-related RNAs.Furthermore,peripheral blood may mediate signaling transmission among tissues to coordinate the molecular changes in the infected individuals.Collectively,these data provide insights into the pathogenesis of COVID-19 at the early stage of infection by the original SARS-CoV-2 strain and its VOCs.

关 键 词：SARS-CoV-2 Variant of concern Subgenomic RNA Rhesus macaque TRANSCRIPTOME 

分 类 号：R563.1[医药卫生—呼吸系统]