Differential transcriptomic landscapes of multiple organs from SARS-CoV-2 early infected rhesus macaques.

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; Yong-liang Zhao; Bo Huang; Xiao-zhong Peng; Ying Yang; Chuan Qin; Wei-min Tong; Yun-gui Yang

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Differential transcriptomic landscapes of multiple organs from SARS-CoV-2 early infected rhesus macaques.

Author: Chun-Chun GAO ¹ ; Man LI ² ; Wei DENG ^{3
,

4} ; Chun-Hui MA ⁵ ; Yu-Sheng CHEN ¹ ; Yong-Qiao SUN ¹ ; Tingfu DU ⁶ ; Qian-Lan LIU ¹ ; Wen-Jie LI ¹ ; Bing ZHANG ¹ ; Lihong SUN ⁷ ; Si-Meng LIU ⁵ ; Fengli LI ^{3
,

4} ; Feifei QI ^{3
,

4} ; Yajin QU ^{3
,

4} ; Xinyang GE ¹ ; Jiangning LIU ^{3
,

4} ; Peng WANG ⁵ ; Yamei NIU ⁵ ; Zhiyong LIANG ⁸ ; Yong-Liang ZHAO ¹ ; Bo HUANG ⁹ ; Xiao-Zhong PENG ⁶ ; Ying YANG ¹⁰ ; Chuan QIN ^{3
,

11} ; Wei-Min TONG ¹² ; Yun-Gui YANG ¹³
Author Information

1. 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.
2. Department of Pathology, Beijing Ditan Hospital, Capital Medical University, Beijing, 100000, China.
3. NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases
4. Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, 100021, China.
5. 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.
6. Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, 650031, China.
7. Center for Experimental Animal Research, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China.
8. 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.
9. 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.
10. 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. yingyang@big.ac.cn.
11. Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, 100021, China. qinchuan@pumc.edu.cn.
12. 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. wmtong@ibms.pumc.edu.cn.
13. 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. ygyang@big.ac.cn.
Publication Type:Research Support, Non-U.S. Gov't
Keywords: NRP1; SARS-CoV-2; central nervous system; inflammation; rhesus macaque; viral encephalitis
MeSH: Animals; COVID-19/genetics*; Macaca mulatta; SARS-CoV-2/genetics*; Transcriptome
From: Protein & Cell 2022;13(12):920-939
CountryChina
Language:English
Abstract: SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, 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 significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis 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 transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.