Volume 13 Issue 12
Dec.  2022
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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. Differential transcriptomic landscapes of multiple organs from SARS-CoV-2 early infected rhesus macaques[J]. Protein&Cell, 2022, 13(12): 920-939. doi: 10.1007/s13238-022-00915-5
Citation: 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. Differential transcriptomic landscapes of multiple organs from SARS-CoV-2 early infected rhesus macaques[J]. Protein&Cell, 2022, 13(12): 920-939. doi: 10.1007/s13238-022-00915-5

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

doi: 10.1007/s13238-022-00915-5

We thank members from biosafety level 3 (ABSL3) laboratories of Peking Union Medical College for providing support to this project.

  • Received Date: 2022-02-23
  • Rev Recd Date: 2022-03-08
  • 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.
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  • [1]
    Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, Vanstapel A, Werlein C, Stark H, Tzankov A et al (2020) Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19. N Engl J Med 383:120-128
    Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT et al (2000) Gene ontology:tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25:25-29
    Bates TA, Leier HC, Lyski ZL, McBride SK, Coulter FJ, Weinstein JB, Goodman JR, Lu Z, Siegel SAR, Sullivan P et al (2021) Neutralization of SARS-CoV-2 variants by convalescent and BNT162b2 vaccinated serum. Nat Commun 12:5135
    Bian X-W, Team tC-P (2020) Autopsy of COVID-19 victims in China. Natl Sci Rev 7:1414-1418
    Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, Fridman WH, Pages F, Trajanoski Z, Galon J (2009) ClueGO:a cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics 25:1091-1093
    Boehm E, Kronig I, Neher RA, Eckerle I, Vetter P, Kaiser L, Centre G, and Geneva Centre for Emerging Viral D (2021) Novel SARS-CoV-2 variants:the pandemics within the pandemic. Clin Microbiol Infect 27:1109-1117
    Bolger AM, Lohse M, Usadel B (2014) Trimmomatic:a flexible trimmer for Illumina sequence data. Bioinformatics 30:2114-2120
    Cai Y, Zhang J, Xiao T, Lavine CL, Rawson S, Peng H, Zhu H, Anand K, Tong P, Gautam A et al (2021) Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 variants. Science 373:642-648
    Cantuti-Castelvetri L, Ojha R, Pedro LD, Djannatian M, Franz J, Kuivanen S, van der Meer F, Kallio K, Kaya T, Anastasina M et al (2020) Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science 370:856-860
    Cao X (2021) ISG15 secretion exacerbates inflammation in SARS-CoV-2 infection. Nat Immunol 22:1360-1362
    Chapin JC, Hajjar KA (2015) Fibrinolysis and the control of blood coagulation. Blood Rev 29:17-24
    Chen C, Chen H, Zhang Y, Thomas HR, Frank MH, He Y, Xia R (2020) TBtools:an integrative toolkit developed for interactive analyses of big biological data. Mol Plant 13:1194-1202
    Chen L, Marishta A, Ellison CE, Verzi MP (2021) Identification of transcription factors regulating SARS-CoV-2 entry genes in the intestine. Cell Mol Gastroenterol Hepatol 11:181-184
    Conway JR, Lex A, Gehlenborg N (2017) UpSetR:an R package for the visualization of intersecting sets and their properties. Bioinformatics 33:2938-2940
    da Huang W, Sherman BT, Lempicki RA (2009a) Bioinformatics enrichment tools:paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37:1-13
    da Huang W, Sherman BT, Lempicki RA (2009b) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44-57
    Daly JL, Simonetti B, Klein K, Chen KE, Williamson MK, Anton-Plagaro C, Shoemark DK, Simon-Gracia L, Bauer M, Hollandi R et al (2020) Neuropilin-1 is a host factor for SARS-CoV-2 infection. Science 370:861-865
    Davies J, Randeva HS, Chatha K, Hall M, Spandidos DA, Karteris E, Kyrou I (2020) Neuropilin1 as a new potential SARS-CoV-2 infection mediator implicated in the neurologic features and central nervous system involvement of COVID19. Mol Med Rep 22:4221-4226
    Demidenko E (2018) The next-generation K-means algorithm. Stat Anal Data Min 11:153-166
    Deng W, Bao L, Liu J, Xiao C, Liu J, Xue J, Lv Q, Qi F, Gao H, Yu P et al (2020) Primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques. Science 369:818-823
    Dey J, Alam MT, Chandra S, Gupta J, Ray U, Srivastava AK, Tripathi PP (2021) Neuroinvasion of SARS-CoV-2 may play a role in the breakdown of the respiratory center of the brain. J Med Virol 93:1296-1303
    Fainardi V, Longo F, Chetta A, Esposito S, Pisi G (2020) SARS-CoV-2 infection in patients with cystic fibrosis. An overview. Acta Biomed 91:e2020035
    Gao Q, Bao L, Mao H, Wang L, Xu K, Yang M, Li Y, Zhu L, Wang N, Lv Z et al (2020) Development of an inactivated vaccine candidate for SARS-CoV-2. Science 369:77-81
    Garcia-Beltran WF, Lam EC, St Denis K, Nitido AD, Garcia ZH, Hauser BM, Feldman J, Pavlovic MN, Gregory DJ, Poznansky MC et al (2021) Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity. Cell 184:2372-2383
    Giordo R, Paliogiannis P, Mangoni AA, Pintus G (2021) SARS-CoV-2 and endothelial cell interaction in COVID-19:molecular perspectives. Vasc Biol 3:R15-R23
    Gudowska-Sawczuk M, Mroczko B (2021) The role of Neuropilin-1 (NRP-1) in SARS-CoV-2 infection:review. J Clin Med 10:2772
    Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, Bikdeli B, Ahluwalia N, Ausiello JC, Wan EY et al (2020) Extrapulmonary manifestations of COVID-19. Nat Med 26:1017-1032
    Han H, Cho JW, Lee S, Yun A, Kim H, Bae D, Yang S, Kim CY, Lee M, Kim E et al (2018) TRRUST v2:an expanded reference database of human and mouse transcriptional regulatory interactions. Nucleic Acids Res 46:D380-D386
    Han H, Yang L, Liu R, Liu F, Wu KL, Li J, Liu XH, Zhu CL (2020a) Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med 58:1116-1120
    Han X, Zhou Z, Fei L, Sun H, Wang R, Chen Y, Chen H, Wang J, Tang H, Ge W et al (2020b) Construction of a human cell landscape at single-cell level. Nature 581:303-309
    Harrison AG, Lin T, Wang P (2020) Mechanisms of SARS-CoV-2 transmission and pathogenesis. Trends Immunol 41:1100-1115
    Harvey WT, Carabelli AM, Jackson B, Gupta RK, Thomson EC, Harrison EM, Ludden C, Reeve R, Rambaut A, Consortium C-GU et al (2021) SARS-CoV-2 variants, spike mutations and immune escape. Nat Rev Microbiol 19:409-424
    Karim SSA, Karim QA (2021) Omicron SARS-CoV-2 variant:a new chapter in the COVID-19 pandemic. Lancet 398:2126-2128
    Kim MS, Pinto SM, Getnet D, Nirujogi RS, Manda SS, Chaerkady R, Madugundu AK, Kelkar DS, Isserlin R, Jain S et al (2014) A draft map of the human proteome. Nature 509:575-581
    Kim D, Langmead B, Salzberg SL (2015) HISAT:a fast spliced aligner with low memory requirements. Nat Methods 12:357-360
    Koyuncu OO, Hogue IB, Enquist LW (2013) Virus infections in the nervous system. Cell Host Microbe 13:379-393
    Kudose S, Batal I, Santoriello D, Xu K, Barasch J, Peleg Y, Canetta P, Ratner LE, Marasa M, Gharavi AG et al (2020) Kidney biopsy findings in patients with COVID-19. J Am Soc Nephrol 31:1959-1968
    Lamers MM, Beumer J, van der Vaart J, Knoops K, Puschhof J, Breugem TI, Ravelli RBG, Paul van Schayck J, Mykytyn AZ, Duimel HQ et al (2020) SARS-CoV-2 productively infects human gut enterocytes. Science 369:50-54
    Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R, Genome Project Data Processing S (2009) The sequence alignment/map format and SAMtools. Bioinformatics 25:2078-2079
    Li MY, Li L, Zhang Y, Wang XS (2020) Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect Dis Poverty 9:45
    Liao Y, Smyth GK, Shi W (2014) featureCounts:an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30:923-930
    Martin M (2011) Cutadapt removes adapter sequences from high-throughput sequencing reads. Embnet J 17:10-12
    Mistry P, Barmania F, Mellet J, Peta K, Strydom A, Viljoen IM, James W, Gordon S, Pepper MS (2021) SARS-CoV-2 variants, vaccines, and host immunity. Front Immunol 12:809244
    Mostafavi S, Yoshida H, Moodley D, LeBoite H, Rothamel K, Raj T, Ye CJ, Chevrier N, Zhang SY, Feng T et al (2016) Parsing the interferon transcriptional network and its disease associations. Cell 164:564-578
    Muszbek L, Bereczky Z, Bagoly Z, Komaromi I, Katona E (2011) Factor XIII:a coagulation factor with multiple plasmatic and cellular functions. Physiol Rev 91:931-972
    Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, Hoang CD, Diehn M, Alizadeh AA (2015) Robust enumeration of cell subsets from tissue expression profiles. Nat Methods 12:453-457
    Nie X, Qian L, Sun R, Huang B, Dong X, Xiao Q, Zhang Q, Lu T, Yue L, Chen S et al (2021) Multi-organ proteomic landscape of COVID-19 autopsies. Cell 184:775-791
    Palta S, Saroa R, Palta A (2014) Overview of the coagulation system. Indian J Anaesth 58:515-523
    Peiris JS, Chu CM, Cheng VC, Chan KS, Hung IF, Poon LL, Law KI, Tang BS, Hon TY, Chan CS et al (2003) Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia:a prospective study. Lancet 361:1767-1772
    Peyvandi F, Garagiola I, Baronciani L (2011) Role of von Willebrand factor in the haemostasis. Blood Transfus 9(Suppl 2):s3-8
    Puelles VG, Lutgehetmann M, Lindenmeyer MT, Sperhake JP, Wong MN, Allweiss L, Chilla S, Heinemann A, Wanner N, Liu S et al (2020) Multiorgan and renal tropism of SARS-CoV-2. N Engl J Med 383:590-592
    Quinlan AR, Hall IM (2010) BEDTools:a flexible suite of utilities for comparing genomic features. Bioinformatics 26:841-842
    Ramani A, Muller L, Ostermann PN, Gabriel E, Abida-Islam P, Muller-Schiffmann A, Mariappan A, Goureau O, Gruell H, Walker A et al (2020) SARS-CoV-2 targets neurons of 3D human brain organoids. EMBO J 39:e106230
    Robinson MD, McCarthy DJ, Smyth GK (2010) edgeR:a bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26:139-140
    Ronco C, Reis T, Husain-Syed F (2020) Management of acute kidney injury in patients with COVID-19. Lancet Respir Med 8:738-742
    Ruan Q, Yang K, Wang W, Jiang L, Song J (2020) Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 46:846-848
    Sa Ribero M, Jouvenet N, Dreux M, Nisole S (2020) Interplay between SARS-CoV-2 and the type I interferon response. PLoS Pathog 16:e1008737
    Schreiber RD, Hicks LJ, Celada A, Buchmeier NA, Gray PW (1985) Monoclonal antibodies to murine gamma-interferon which differentially modulate macrophage activation and antiviral activity. J Immunol 134:1609-1618
    Schwabenland M, Salie H, Tanevski J, Killmer S, Lago MS, Schlaak AE, Mayer L, Matschke J, Puschel K, Fitzek A et al (2021) Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions. Immunity 54:1594-1610
    Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape:a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498-2504
    Shao X, Liao J, Li C, Lu X, Cheng J, Fan X (2020) Cell TalkDB:a manually curated database of ligand-receptor interactions in humans and mice. Brief Bioinform 22:269
    Sica A, Mantovani A (2012) Macrophage plasticity and polarization:in vivo veritas. J Clin Invest 122:787-795
    Song E, Zhang C, Israelow B, Lu-Culligan A, Prado AV, Skriabine S, Lu P, Weizman OE, Liu F, Dai Y et al (2021) Neuroinvasion of SARS-CoV-2 in human and mouse brain. J Exp Med. https://doi.org/10.1084/jem.20202135
    Stolp B, Stern M, Ambiel I, Hofmann K, Morath K, Gallucci L, Cortese M, Bartenschlager R, Ruggieri A, Graw F et al (2022) SARS-CoV-2 variants of concern display enhanced intrinsic pathogenic properties and expanded organ tropism in mouse models. Cell Rep 38:110387
    Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES et al (2005) Gene set enrichment analysis:a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 102:15545-15550
    Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, Simonovic M, Doncheva NT, Morris JH, Bork P et al (2019) STRING v11:protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 47:D607-D613
    Tang X, Yang M, Duan Z, Liao Z, Liu L, Cheng R, Fang M, Wang G, Liu H, Xu J, et al (2020) Transferrin receptor is another receptor for SARS-CoV-2 entry. bioRxiv
    Taquet M, Geddes JR, Husain M, Luciano S, Harrison PJ (2021) 6-month neurological and psychiatric outcomes in 236379 survivors of COVID-19:a retrospective cohort study using electronic health records. Lancet Psychiatry 8:416-427
    Thorvaldsdottir H, Robinson JT, Mesirov JP (2013) Integrative Genomics Viewer (IGV):high-performance genomics data visualization and exploration. Brief Bioinform 14:178-192
    Tian S, Xiong Y, Liu H, Niu L, Guo J, Liao M, Xiao SY (2020) Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies. Mod Pathol 33:1007-1014
    Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ (2000) A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem 275:33238-33243
    Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, Mehra MR, Schuepbach RA, Ruschitzka F, Moch H (2020) Endothelial cell infection and endotheliitis in COVID-19. Lancet 395:1417-1418
    Vial C, Calderon JF, Klein AD (2021) NPC1 as a modulator of disease severity and viral entry of SARS-CoV- 2. Curr Mol Med 21:2-4
    von Weyhern CH, Kaufmann I, Neff F, Kremer M (2020) Early evidence of pronounced brain involvement in fatal COVID-19 outcomes. The Lancet 395:e109
    Wang GF, Li W, Li K (2010) Acute encephalopathy and encephalitis caused by influenza virus infection. Curr Opin Neurol 23:305-311
    Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y et al (2020) Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 323:1061-1069
    Wang R, Zhang Q, Ge J, Ren W, Zhang R, Lan J, Ju B, Su B, Yu F, Chen P et al (2021a) Analysis of SARS-CoV-2 variant mutations reveals neutralization escape mechanisms and the ability to use ACE2 receptors from additional species. Immunity 54:1611-1621
    Wang S, Qiu Z, Hou Y, Deng X, Xu W, Zheng T, Wu P, Xie S, Bian W, Zhang C et al (2021b) AXL is a candidate receptor for SARS-CoV-2 that promotes infection of pulmonary and bronchial epithelial cells. Cell Res 31:126-140
    Wenzel J, Lampe J, Muller-Fielitz H, Schuster R, Zille M, Muller K, Krohn M, Korbelin J, Zhang L, Ozorhan U et al (2021) The SARS-CoV-2 main protease M(pro) causes microvascular brain pathology by cleaving NEMO in brain endothelial cells. Nat Neurosci 24:1522-1533
    Wichmann D (2020) Autopsy findings and venous thromboembolism in patients with COVID-19. Ann Intern Med 173:1030
    Wichmann D, Sperhake JP, Lutgehetmann M, Steurer S, Edler C, Heinemann A, Heinrich F, Mushumba H, Kniep I, Schroder AS et al (2020) Autopsy findings and venous thromboembolism in patients with COVID-19:a prospective cohort study. Ann Intern Med 173:268-277
    Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, Graham BS, McLellan JS (2020) Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 367:1260-1263
    Yang M, Chen S, Huang B, Zhong JM, Su H, Chen YJ, Cao Q, Ma L, He J, Li XF et al (2020) Pathological findings in the testes of COVID-19 patients:clinical implications. Eur Urol Focus 6:1124-1129
    Yates AD, Achuthan P, Akanni W, Allen J, Allen J, Alvarez-Jarreta J, Amode MR, Armean IM, Azov AG, Bennett R et al (2020) Ensembl 2020. Nucleic Acids Res 48:D682-D688
    Yu F, Yan L, Wang N, Yang S, Wang L, Tang Y, Gao G, Wang S, Ma C, Xie R et al (2020a) Quantitative detection and viral load analysis of SARS-CoV-2 in infected patients. Clin Infect Dis 71:793-798
    Yu P, Qi F, Xu Y, Li F, Liu P, Liu J, Bao L, Deng W, Gao H, Xiang Z et al (2020b) Age-related rhesus macaque models of COVID-19. Animal Model Exp Med 3:93-97
    Zhang BZ, Chu H, Han S, Shuai H, Deng J, Hu YF, Gong HR, Lee AC, Zou Z, Yau T et al (2020a) SARS-CoV-2 infects human neural progenitor cells and brain organoids. Cell Res 30:928-931
    Zhang C, Shi L, Wang F-S (2020b) Liver injury in COVID-19:management and challenges. Lancet Gastroenterol Hepatol 5:428-430
    Zhang L, Zhou L, Bao L, Liu J, Zhu H, Lv Q, Liu R, Chen W, Tong W, Wei Q et al (2021) SARS-CoV-2 crosses the blood-brain barrier accompanied with basement membrane disruption without tight junctions alteration. Signal Transduct Target Ther 6:337
    Zheng YY, Ma YT, Zhang JY, Xie X (2020) COVID-19 and the cardiovascular system. Nat Rev Cardiol 17:259-260
    Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X et al (2020) Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China:a retrospective cohort study. Lancet 395:1054-1062
    Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R et al (2020) A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 382:727-733
    Ziegler CGK, Allon SJ, Nyquist SK, Mbano IM, Miao VN, Tzouanas CN, Cao Y, Yousif AS, Bals J, Hauser BM et al (2020) SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues. Cell 181:1016-1035
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