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Cell
05 28, 2020;181 (5): 1016-1035.e19.

SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues.

Carly G K Ziegler, Samuel J Allon, Sarah K Nyquist, Ian M Mbano, Vincent N Miao, Constantine N Tzouanas, Yuming Cao, Ashraf S Yousif, Julia Bals, Blake M Hauser, Jared Feldman, Christoph Muus, Marc H Wadsworth, Samuel W Kazer, Travis K Hughes, Benjamin Doran, G James Gatter, Marko Vukovic, Faith Taliaferro, Benjamin E Mead, Zhiru Guo, Jennifer P Wang, Delphine Gras, Magali Plaisant, Meshal Ansari, Ilias Angelidis, Heiko Adler, Jennifer M S Sucre, Chase J Taylor, Brian Lin, Avinash Waghray, Vanessa Mitsialis, Daniel F Dwyer, Kathleen M Buchheit, Joshua A Boyce, Nora A Barrett, Tanya M Laidlaw, Shaina L Carroll, Lucrezia Colonna, Victor Tkachev, Christopher W Peterson, Alison Yu, Hengqi Betty Zheng, Hannah P Gideon, Caylin G Winchell, Philana Ling Lin, Colin D Bingle, Scott B Snapper, Jonathan A Kropski, Fabian J Theis, Herbert B Schiller, Laure-Emmanuelle Zaragosi, Pascal Barbry, Alasdair Leslie, Hans-Peter Kiem, JoAnne L Flynn, Sarah M Fortune, Bonnie Berger, Robert W Finberg, Leslie S Kean, Manuel Garber, Aaron G Schmidt, Daniel Lingwood, Alex K Shalek, Jose Ordovas-Montanes, HCA Lung Biological Network. Electronic address: lung-network@humancellatlas.org, HCA Lung Biological Network
Author Information
  1. Carly G K Ziegler: Program in Health Sciences & Technology, Harvard Medical School & Massachusetts Institute of Technology, Boston, MA 02115, USA; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Graduate Program in Biophysics, Harvard University, Cambridge, MA 02138, USA.
  2. Samuel J Allon: Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  3. Sarah K Nyquist: Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Program in Computational & Systems Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Computer Science & Artificial Intelligence Lab, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  4. Ian M Mbano: Africa Health Research Institute, Durban, South Africa; School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
  5. Vincent N Miao: Program in Health Sciences & Technology, Harvard Medical School & Massachusetts Institute of Technology, Boston, MA 02115, USA; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  6. Constantine N Tzouanas: Program in Health Sciences & Technology, Harvard Medical School & Massachusetts Institute of Technology, Boston, MA 02115, USA; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  7. Yuming Cao: University of Massachusetts Medical School, Worcester, MA 01655, USA.
  8. Ashraf S Yousif: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  9. Julia Bals: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  10. Blake M Hauser: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
  11. Jared Feldman: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Program in Virology, Harvard Medical School, Boston, MA 02115, USA.
  12. Christoph Muus: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; John A. Paulson School of Engineering & Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
  13. Marc H Wadsworth: Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  14. Samuel W Kazer: Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  15. Travis K Hughes: Program in Health Sciences & Technology, Harvard Medical School & Massachusetts Institute of Technology, Boston, MA 02115, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Program in Immunology, Harvard Medical School, Boston, MA 02115, USA.
  16. Benjamin Doran: Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA; Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA 02115, USA.
  17. G James Gatter: Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  18. Marko Vukovic: Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  19. Faith Taliaferro: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA 02115, USA.
  20. Benjamin E Mead: Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  21. Zhiru Guo: University of Massachusetts Medical School, Worcester, MA 01655, USA.
  22. Jennifer P Wang: University of Massachusetts Medical School, Worcester, MA 01655, USA.
  23. Delphine Gras: Aix-Marseille University, INSERM, INRA, C2VN, Marseille, France.
  24. Magali Plaisant: Universit�� C��te d'Azur, CNRS, IPMC, Sophia-Antipolis, France.
  25. Meshal Ansari: Comprehensive Pneumology Center & Institute of Lung Biology and Disease, Helmholtz Zentrum M��nchen, Munich, Germany; German Center for Lung Research, Munich, Germany; Institute of Computational Biology, Helmholtz Zentrum M��nchen, Munich, Germany.
  26. Ilias Angelidis: Comprehensive Pneumology Center & Institute of Lung Biology and Disease, Helmholtz Zentrum M��nchen, Munich, Germany; German Center for Lung Research, Munich, Germany.
  27. Heiko Adler: German Center for Lung Research, Munich, Germany; Research Unit Lung Repair and Regeneration, Helmholtz Zentrum M��nchen, Munich, Germany.
  28. Jennifer M S Sucre: Division of Neonatology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  29. Chase J Taylor: Divison of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  30. Brian Lin: Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
  31. Avinash Waghray: Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
  32. Vanessa Mitsialis: Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA 02115, USA; Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA 02115, USA.
  33. Daniel F Dwyer: Division of Allergy and Clinical Immunology, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  34. Kathleen M Buchheit: Division of Allergy and Clinical Immunology, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  35. Joshua A Boyce: Division of Allergy and Clinical Immunology, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  36. Nora A Barrett: Division of Allergy and Clinical Immunology, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  37. Tanya M Laidlaw: Division of Allergy and Clinical Immunology, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  38. Shaina L Carroll: University of California, Berkeley, CA 94720, USA.
  39. Lucrezia Colonna: University of Washington, Seattle, WA 98195, USA.
  40. Victor Tkachev: Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA; Dana Farber Cancer Institute, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
  41. Christopher W Peterson: Stem Cell & Gene Therapy Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Medicine, University of Washington, Seattle, WA 98195, USA.
  42. Alison Yu: Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA; Division of Gastroenterology and Hepatology, Seattle Children's Hospital, Seattle, WA 98145, USA.
  43. Hengqi Betty Zheng: University of Washington, Seattle, WA 98195, USA; Division of Gastroenterology and Hepatology, Seattle Children's Hospital, Seattle, WA 98145, USA.
  44. Hannah P Gideon: Department of Microbiology & Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA; Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
  45. Caylin G Winchell: Department of Microbiology & Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA; Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
  46. Philana Ling Lin: Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, USA; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.
  47. Colin D Bingle: Department of Infection, Immunity & Cardiovascular Disease, The Medical School and The Florey Institute for Host Pathogen Interactions, University of Sheffield, Sheffield, S10 2TN, UK.
  48. Scott B Snapper: Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA 02115, USA; Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA 02115, USA.
  49. Jonathan A Kropski: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37240, USA; Department of Veterans Affairs Medical Center, Nashville, TN 37212, USA.
  50. Fabian J Theis: Institute of Computational Biology, Helmholtz Zentrum M��nchen, Munich, Germany.
  51. Herbert B Schiller: Comprehensive Pneumology Center & Institute of Lung Biology and Disease, Helmholtz Zentrum M��nchen, Munich, Germany; German Center for Lung Research, Munich, Germany.
  52. Laure-Emmanuelle Zaragosi: Universit�� C��te d'Azur, CNRS, IPMC, Sophia-Antipolis, France.
  53. Pascal Barbry: Universit�� C��te d'Azur, CNRS, IPMC, Sophia-Antipolis, France.
  54. Alasdair Leslie: Africa Health Research Institute, Durban, South Africa; School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa; Department of Infection & Immunity, University College London, London, UK.
  55. Hans-Peter Kiem: Stem Cell & Gene Therapy Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Medicine, University of Washington, Seattle, WA 98195, USA.
  56. JoAnne L Flynn: Department of Microbiology & Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA; Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
  57. Sarah M Fortune: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
  58. Bonnie Berger: Computer Science & Artificial Intelligence Lab, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Mathematics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  59. Robert W Finberg: University of Massachusetts Medical School, Worcester, MA 01655, USA.
  60. Leslie S Kean: Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA; Dana Farber Cancer Institute, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
  61. Manuel Garber: University of Massachusetts Medical School, Worcester, MA 01655, USA.
  62. Aaron G Schmidt: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
  63. Daniel Lingwood: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  64. Alex K Shalek: Program in Health Sciences & Technology, Harvard Medical School & Massachusetts Institute of Technology, Boston, MA 02115, USA; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Graduate Program in Biophysics, Harvard University, Cambridge, MA 02138, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Program in Computational & Systems Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Program in Immunology, Harvard Medical School, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address: shalek@mit.edu.
  65. Jose Ordovas-Montanes: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Program in Immunology, Harvard Medical School, Boston, MA 02115, USA; Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address: jose.ordovas-montanes@childrens.harvard.edu.
PMID: 32413319 DOI: 10.1016/j.cell.2020.04.035

Abstract

There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes the disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues and the factors that regulate ACE2 expression remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 among tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discovered that ACE2 is a human interferon-stimulated gene (ISG) in vitro using airway epithelial cells and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection.

Keywords

ACE2 COVID-19 ISG SARS-CoV-2 human influenza interferon mouse non-human primate scRNA-seq

References

  1. N Engl J Med. 2020 Apr 30;382(18):1708-1720 [PMID: 32109013]
  2. Adv Exp Med Biol. 1980;130:1-27 [PMID: 6250339]
  3. Virology. 2004 Nov 10;329(1):11-7 [PMID: 15476870]
  4. Clin Transl Immunology. 2019 Aug 05;8(8):e1073 [PMID: 31406574]
  5. J Virol. 2000 Aug;74(15):6964-74 [PMID: 10888635]
  6. Science. 2020 Mar 13;367(6483):1260-1263 [PMID: 32075877]
  7. Nat Rev Immunol. 2017 Jan;17(1):7-20 [PMID: 27890913]
  8. Nat Commun. 2014 May 06;5:3594 [PMID: 24800825]
  9. Lancet. 2020 Feb 22;395(10224):565-574 [PMID: 32007145]
  10. J Clin Invest. 2019 Jul 29;129(9):3625-3639 [PMID: 31355779]
  11. Elife. 2017 Dec 05;6: [PMID: 29206104]
  12. J Virol. 2014 Apr;88(8):4558-71 [PMID: 24501414]
  13. Pathog Immun. 2016 Spring;1(1):107-116 [PMID: 27500281]
  14. Nature. 2018 Aug;560(7720):649-654 [PMID: 30135581]
  15. J Virol. 2011 May;85(9):4234-45 [PMID: 21325418]
  16. Genome Res. 2012 Sep;22(9):1798-812 [PMID: 22955990]
  17. Pathog Dis. 2013 Nov;69(2):87-100 [PMID: 23821437]
  18. Cell. 2015 May 21;161(5):1202-1214 [PMID: 26000488]
  19. Cell Host Microbe. 2016 Feb 10;19(2):181-93 [PMID: 26867177]
  20. J Virol. 2005 Aug;79(16):10190-9 [PMID: 16051812]
  21. Drug Discov Ther. 2020;14(1):58-60 [PMID: 32147628]
  22. Virol J. 2016 Feb 06;13:24 [PMID: 26852031]
  23. FEBS Lett. 2002 Dec 4;532(1-2):107-10 [PMID: 12459472]
  24. Nature. 2012 Mar 25;484(7395):519-23 [PMID: 22446628]
  25. BMJ Open. 2020 Oct 7;10(10):e037295 [PMID: 33033018]
  26. Nat Med. 2019 Jul;25(7):1153-1163 [PMID: 31209336]
  27. Nat Med. 2020 Jul;26(7):1033-1036 [PMID: 32398876]
  28. Eur Arch Otorhinolaryngol. 2020 Aug;277(8):2251-2261 [PMID: 32253535]
  29. J Infect Dis. 2020 Jul 23;222(4):556-563 [PMID: 32526012]
  30. Cell. 2020 Apr 16;181(2):281-292.e6 [PMID: 32155444]
  31. Development. 2019 Oct 23;146(20): [PMID: 31558434]
  32. Nature. 2003 Nov 27;426(6965):450-4 [PMID: 14647384]
  33. Cell Syst. 2018 Jun 27;6(6):679-691.e4 [PMID: 29886109]
  34. Immunity. 2020 Oct 13;53(4):878-894.e7 [PMID: 33053333]
  35. Annu Rev Virol. 2014 Nov 1;1:261-283 [PMID: 25599080]
  36. J Cyst Fibros. 2004 Aug;3 Suppl 2:59-62 [PMID: 15463928]
  37. Genome Biol. 2018 Feb 6;19(1):15 [PMID: 29409532]
  38. J Infect Dis. 2012 Dec 1;206(11):1685-94 [PMID: 22829640]
  39. Nucleic Acids Res. 2013 Jan;41(Database issue):D1040-6 [PMID: 23203888]
  40. Science. 2015 Mar 6;347(6226):1259038 [PMID: 25745177]
  41. J Biol Chem. 2009 Aug 28;284(35):23177-81 [PMID: 19487698]
  42. Nat Commun. 2020 Oct 12;11(1):5139 [PMID: 33046696]
  43. Nature. 2020 May;581(7809):465-469 [PMID: 32235945]
  44. J Pathol. 2004 Jun;203(2):622-30 [PMID: 15141376]
  45. Gigascience. 2020 Dec 26;9(12): [PMID: 33367645]
  46. J Clin Invest. 2017 Jan 3;127(1):103-105 [PMID: 27941242]
  47. Am J Respir Cell Mol Biol. 2019 Jul;61(1):31-41 [PMID: 30995076]
  48. Nature. 2012 Sep 6;489(7414):91-100 [PMID: 22955619]
  49. N Engl J Med. 2020 Mar 5;382(10):929-936 [PMID: 32004427]
  50. Nat Med. 2020 Apr;26(4):511-518 [PMID: 32251406]
  51. Front Immunol. 2018 Sep 28;9:2229 [PMID: 30323812]
  52. Nat Methods. 2014 Jul;11(7):740-2 [PMID: 24836921]
  53. Science. 2014 Jun 27;344(6191):1492-6 [PMID: 24970081]
  54. J Virol. 2011 May;85(9):4122-34 [PMID: 21325420]
  55. Am J Respir Cell Mol Biol. 2013 Jun;48(6):742-8 [PMID: 23418343]
  56. J Interferon Cytokine Res. 2006 Jul;26(7):462-72 [PMID: 16800785]
  57. mBio. 2017 May 9;8(3): [PMID: 28487426]
  58. Virology. 2006 Sep 30;353(2):474-81 [PMID: 16860835]
  59. J Pathol. 2004 Jun;203(2):631-7 [PMID: 15141377]
  60. Nat Rev Drug Discov. 2020 Mar;19(3):149-150 [PMID: 32127666]
  61. Genome Biol. 2016 Sep 19;17(1):188 [PMID: 27640647]
  62. J Exp Med. 2020 Jan 6;217(1): [PMID: 31821443]
  63. Nat Commun. 2018 Sep 6;9(1):3603 [PMID: 30190477]
  64. Nat Microbiol. 2020 Apr;5(4):562-569 [PMID: 32094589]
  65. J Virol. 2010 Dec;84(24):12658-64 [PMID: 20926566]
  66. Eur Respir J. 2012 May;39(5):1197-205 [PMID: 22005912]
  67. Bioinformatics. 2018 Dec 1;34(23):4121-4123 [PMID: 29790939]
  68. JAMA. 2020 Feb 25;323(8):707-708 [PMID: 31971553]
  69. Nat Biotechnol. 2018 Jun;36(5):411-420 [PMID: 29608179]
  70. J Virol. 2018 Apr 13;92(9): [PMID: 29467318]
  71. Nat Commun. 2018 Oct 25;9(1):4438 [PMID: 30361514]
  72. Lancet Infect Dis. 2020 May;20(5):533-534 [PMID: 32087114]
  73. Nature. 2005 Jul 7;436(7047):112-6 [PMID: 16001071]
  74. Biochem Biophys Res Commun. 2020 May 21;526(1):135-140 [PMID: 32199615]
  75. Bioinformatics. 2010 Jan 1;26(1):139-40 [PMID: 19910308]
  76. Nucleic Acids Res. 2003 Jan 1;31(1):374-8 [PMID: 12520026]
  77. Curr Protoc Mol Biol. 2014 Jul 01;107:4.22.1-4.22.17 [PMID: 24984854]
  78. Lancet Infect Dis. 2020 May;20(5):553-558 [PMID: 32171059]
  79. Semin Immunopathol. 2017 Jul;39(5):529-539 [PMID: 28466096]
  80. Nat Commun. 2014 May 06;5:3595 [PMID: 24800963]
  81. Genome Res. 2016 Oct;26(10):1397-1410 [PMID: 27470110]
  82. Genome Biol. 2019 Mar 27;20(1):66 [PMID: 30917855]
  83. Proc Natl Acad Sci U S A. 2014 May 6;111(18):6756-61 [PMID: 24753610]
  84. N Engl J Med. 2020 Mar 19;382(12):1177-1179 [PMID: 32074444]
  85. J Virol. 2007 Jan;81(2):813-21 [PMID: 17079315]
  86. F1000Res. 2016 Aug 31;5:2122 [PMID: 27909575]
  87. Nat Rev Immunol. 2008 Nov;8(11):889-95 [PMID: 18927577]
  88. J Exp Med. 2020 May 4;217(5): [PMID: 32289152]
  89. J Virol. 2011 Jan;85(2):873-82 [PMID: 21068237]
  90. Science. 2020 May 29;368(6494):1012-1015 [PMID: 32303590]
  91. Antiviral Res. 2020 Apr;176:104742 [PMID: 32057769]
  92. Cell Rep. 2018 Dec 4;25(10):2689-2703.e3 [PMID: 30517858]
  93. Nat Microbiol. 2020 Apr;5(4):536-544 [PMID: 32123347]
  94. EMBO J. 1991 Oct;10(10):2813-9 [PMID: 1915264]
  95. Lancet. 2020 Feb 15;395(10223):497-506 [PMID: 31986264]
  96. Elife. 2018 Feb 16;7: [PMID: 29451492]
  97. EMBO J. 2020 May 18;39(10):e105114 [PMID: 32246845]
  98. Immunity. 2006 Sep;25(3):373-81 [PMID: 16979569]
  99. Nature. 2013 Jun 13;498(7453):236-40 [PMID: 23685454]
  100. Biochem Biophys Res Commun. 2004 Jul 9;319(4):1216-21 [PMID: 15194496]
  101. Nat Genet. 2003 Mar;33(3):388-91 [PMID: 12590259]
  102. Nat Rev Immunol. 2020 May;20(5):308-320 [PMID: 32015472]
  103. Cell. 2019 Jul 25;178(3):714-730.e22 [PMID: 31348891]
  104. BMC Biol. 2018 Jun 5;16(1):62 [PMID: 29871632]
  105. Nat Biotechnol. 2020 Feb;38(2):147-150 [PMID: 31937974]
  106. J Virol. 2019 Mar 5;93(6): [PMID: 30626688]
  107. Sci Adv. 2020 Jul 31;6(31): [PMID: 32937591]
  108. J Vis Exp. 2013 Aug 10;(78): [PMID: 23963491]
  109. Science. 1994 Jun 24;264(5167):1918-21 [PMID: 8009221]
  110. Nat Med. 2005 Aug;11(8):875-9 [PMID: 16007097]
  111. Annu Rev Microbiol. 2019 Sep 8;73:529-557 [PMID: 31226023]
  112. Emerg Microbes Infect. 2019;8(1):1763-1776 [PMID: 31826721]
  113. Nature. 2020 Sep;585(7824):268-272 [PMID: 32396922]
  114. J Interferon Cytokine Res. 2015 Apr;35(4):252-64 [PMID: 25714109]
  115. Nat Rev Immunol. 2013 Jul;13(7):499-509 [PMID: 23787991]
  116. Nucleic Acids Res. 2013 Jan;41(Database issue):D171-6 [PMID: 23203885]
  117. JAMA. 2020 May 12;323(18):1843-1844 [PMID: 32159775]
  118. Nat Biotechnol. 2011 May;29(5):436-42 [PMID: 21516085]
  119. J Interferon Cytokine Res. 2004 Jul;24(7):388-90 [PMID: 15296649]
  120. Cell. 2020 Apr 16;181(2):271-280.e8 [PMID: 32142651]
  121. Radiology. 2020 Apr;295(1):18 [PMID: 32003646]
  122. J Cell Biol. 2011 Dec 26;195(7):1071-82 [PMID: 22123832]
  123. Science. 2012 Feb 24;335(6071):936-41 [PMID: 22363001]
  124. Cell. 2020 May 14;181(4):905-913.e7 [PMID: 32333836]
  125. J Virol. 2010 Nov;84(21):11515-22 [PMID: 20739515]
  126. Nat Rev Immunol. 2014 May;14(5):315-28 [PMID: 24762827]
  127. Nature. 2018 Aug;560(7718):319-324 [PMID: 30069044]
  128. Nat Med. 2020 Apr;26(4):502-505 [PMID: 32284613]
  129. Nat Methods. 2017 Apr;14(4):395-398 [PMID: 28192419]
  130. Nature. 2019 Jun;570(7762):528-532 [PMID: 31168092]
  131. Respir Res. 2017 May 4;18(1):84 [PMID: 28472984]
  132. Sci Adv. 2019 Mar 06;5(3):eaau4255 [PMID: 30854425]
  133. Annu Rev Immunol. 2014;32:513-45 [PMID: 24555472]
  134. N Engl J Med. 2020 Apr 23;382(17):1653-1659 [PMID: 32227760]
  135. J Med Virol. 2020 Nov;92(11):2693-2701 [PMID: 32497323]
  136. Gastroenterology. 2020 May;158(6):1831-1833.e3 [PMID: 32142773]
  137. Nat Biotechnol. 2015 May;33(5):495-502 [PMID: 25867923]

Grants

  1. R01 HL128241/NHLBI NIH HHS
  2. R01 HL095791/NHLBI NIH HHS
  3. R01 HL118185/NHLBI NIH HHS
  4. K08 HL130595/NHLBI NIH HHS
  5. R01 HL117945/NHLBI NIH HHS
  6. R33 AI116184/NIAID NIH HHS
  7. U19 AI095219/NIAID NIH HHS
  8. U19 AI057229/NIAID NIH HHS
  9. MR/R006237/1/Medical Research Council
  10. DP2 DA042422/NIDA NIH HHS
  11. UM1 AI126623/NIAID NIH HHS
  12. R01 GM081871/NIGMS NIH HHS
  13. U19 HL129902/NHLBI NIH HHS
  14. MR/S005579/1/Medical Research Council
  15. R37 AI052353/NIAID NIH HHS
  16. K12 HL143886/NHLBI NIH HHS
  17. MR/S035907/1/Medical Research Council
  18. K23 AI139352/NIAID NIH HHS
  19. MR/S036334/1/Medical Research Council
  20. R01 HL145372/NHLBI NIH HHS
  21. T32 GM007753/NIGMS NIH HHS
  22. U19 AI051731/NIAID NIH HHS
  23. K08 HL146943/NHLBI NIH HHS
  24. R01 AI078908/NIAID NIH HHS
  25. MR/K017047/1/Medical Research Council
  26. P30 DK034854/NIDDK NIH HHS
  27. T32 GM087237/NIGMS NIH HHS
  28. K23 HL111113/NHLBI NIH HHS
  29. R01 HL136209/NHLBI NIH HHS
  30. MR/P009581/1/Medical Research Council
  31. R01 AI124378/NIAID NIH HHS
  32. U24 AI118672/NIAID NIH HHS
  33. R01 AI136041/NIAID NIH HHS
  34. UM1 AI126617/NIAID NIH HHS
  35. P01 HL132821/NHLBI NIH HHS
  36. R56 AI139053/NIAID NIH HHS
  37. R01 AI137057/NIAID NIH HHS
  38. MR/R015635/1/Medical Research Council

MeSH Term

Adolescent
Alveolar Epithelial Cells
Angiotensin-Converting Enzyme 2
Animals
Betacoronavirus
COVID-19
Cell Line
Cells, Cultured
Child
Coronavirus Infections
Enterocytes
Goblet Cells
HIV Infections
Humans
Influenza, Human
Interferon Type I
Lung
Macaca mulatta
Mice
Mycobacterium tuberculosis
Nasal Mucosa
Pandemics
Peptidyl-Dipeptidase A
Pneumonia, Viral
Receptors, Virus
SARS-CoV-2
Serine Endopeptidases
Single-Cell Analysis
Tuberculosis
Up-Regulation

Chemicals

Interferon Type I
Receptors, Virus
Peptidyl-Dipeptidase A
ACE2 protein, human
Ace2 protein, mouse
Angiotensin-Converting Enzyme 2
Serine Endopeptidases
TMPRSS2 protein, human
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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