Similarities and Differences in the Acute-Phase Response to SARS-CoV-2 in Rhesus Macaques and African Green Monkeys.

Celeste Coleman, Lara A Doyle-Meyers, Kasi E Russell-Lodrigue, Nadia Golden, Breanna Threeton, Kejing Song, Genevieve Pierre, Carl Baribault, Rudolf P Bohm, Nicholas J Maness, Jay K Kolls, Jay Rappaport, Joseph C Mudd
Author Information
  1. Celeste Coleman: Department of Immunology and Microbiology, Tulane National Primate Research Center, Covington, LA, United States.
  2. Lara A Doyle-Meyers: Department of Immunology and Microbiology, Tulane National Primate Research Center, Covington, LA, United States.
  3. Kasi E Russell-Lodrigue: Department of Immunology and Microbiology, Tulane National Primate Research Center, Covington, LA, United States.
  4. Nadia Golden: Department of Immunology and Microbiology, Tulane National Primate Research Center, Covington, LA, United States.
  5. Breanna Threeton: Department of Immunology and Microbiology, Tulane National Primate Research Center, Covington, LA, United States.
  6. Kejing Song: Center for Translational Research in Infection and Inflammation, Department of Pediatrics and Department of Medicine, Tulane University School of Medicine, New Orleans, LA, United States.
  7. Genevieve Pierre: Center for Translational Research in Infection and Inflammation, Department of Pediatrics and Department of Medicine, Tulane University School of Medicine, New Orleans, LA, United States.
  8. Carl Baribault: Center for Research & Scientific Computing, Tulane University Information Technology, New Orleans, LA, United States.
  9. Rudolf P Bohm: Department of Immunology and Microbiology, Tulane National Primate Research Center, Covington, LA, United States.
  10. Nicholas J Maness: Department of Immunology and Microbiology, Tulane National Primate Research Center, Covington, LA, United States.
  11. Jay K Kolls: Center for Translational Research in Infection and Inflammation, Department of Pediatrics and Department of Medicine, Tulane University School of Medicine, New Orleans, LA, United States.
  12. Jay Rappaport: Department of Immunology and Microbiology, Tulane National Primate Research Center, Covington, LA, United States.
  13. Joseph C Mudd: Department of Immunology and Microbiology, Tulane National Primate Research Center, Covington, LA, United States.

Abstract

Understanding SARS-CoV-2 immune pathology is critical for the development of effective vaccines and treatments. Here, we employed unbiased serial whole-blood transcriptome profiling by weighted gene network correlation analysis (WGCNA) at pre-specified timepoints of infection to understand SARS-CoV-2-related immune alterations in a cohort of rhesus macaques (RMs) and African green monkeys (AGMs) presenting with varying degrees of pulmonary pathology. We found that the bulk of transcriptional changes occurred at day 3 post-infection and normalized to pre-infection levels by 3 weeks. There was evidence of coordination of transcriptional networks in blood (defined by WGCNA) and the nasopharyngeal SARS-CoV-2 burden as well as the absolute monocyte count. Pathway analysis of gene modules revealed prominent regulation of type I and type II interferon stimulated genes (ISGs) in both RMs and AGMs, with the latter species exhibiting a greater breadth of ISG upregulation. Notably, pathways relating to neutrophil degranulation were enriched in blood of SARS-CoV-2 infected AGMs, but not RMs. Our results elude to hallmark similarities as well as differences in the RM and AGM acute response to SARS-CoV-2 infection, and may help guide the selection of particular NHP species in modeling aspects of COVID-19 disease outcome.

Keywords

References

  1. Proc Natl Acad Sci U S A. 2013 Oct 8;110(41):16598-603 [PMID: 24062443]
  2. Nat Microbiol. 2021 Jan;6(1):73-86 [PMID: 33340034]
  3. J Gen Virol. 2008 Oct;89(Pt 10):2359-2376 [PMID: 18796704]
  4. J Leukoc Biol. 2020 Jul;108(1):17-41 [PMID: 32534467]
  5. Emerg Microbes Infect. 2020 Dec;9(1):761-770 [PMID: 32228226]
  6. Nature. 2020 May;581(7809):465-469 [PMID: 32235945]
  7. mBio. 2017 Aug 22;8(4): [PMID: 28830941]
  8. J Microbiol Immunol Infect. 2020 Jun;53(3):368-370 [PMID: 32205092]
  9. PLoS One. 2007 Feb 28;2(2):e257 [PMID: 17330143]
  10. J Gen Virol. 2012 Oct;93(Pt 10):2152-2157 [PMID: 22815273]
  11. Cell. 2021 Jan 21;184(2):460-475.e21 [PMID: 33278358]
  12. Nat Immunol. 2021 Jan;22(1):86-98 [PMID: 33235385]
  13. Int Immunopharmacol. 2020 Dec;89(Pt A):107034 [PMID: 33039966]
  14. N Engl J Med. 2020 Apr 30;382(18):1708-1720 [PMID: 32109013]
  15. J Clin Invest. 2020 Dec 1;130(12):6290-6300 [PMID: 32784290]
  16. Genome Biol. 2014;15(12):550 [PMID: 25516281]
  17. J Clin Invest. 2019 Dec 2;129(12):5474-5488 [PMID: 31710311]
  18. Science. 2020 Oct 23;370(6515): [PMID: 32972995]
  19. SN Compr Clin Med. 2020 Jun 25;:1-8 [PMID: 32838147]
  20. N Engl J Med. 2020 Oct 29;383(18):1757-1766 [PMID: 32329974]
  21. Mucosal Immunol. 2013 Jul;6(4):797-806 [PMID: 23212197]
  22. J Pediatr. 1978 Jul;93(1):28-32 [PMID: 206677]
  23. J Leukoc Biol. 2009 Mar;85(3):344-51 [PMID: 18955543]
  24. Blood. 1993 Jul 1;82(1):182-91 [PMID: 7686786]
  25. J Virol. 2007 Apr;81(7):3428-36 [PMID: 17251292]
  26. J Med Virol. 2020 Oct;92(10):2055-2066 [PMID: 32369208]
  27. Am J Pathol. 2021 Feb;191(2):274-282 [PMID: 33171111]
  28. Immun Inflamm Dis. 2020 Mar;8(1):106-123 [PMID: 32031762]
  29. Nat Commun. 2021 Jan 22;12(1):541 [PMID: 33483492]
  30. Nat Commun. 2020 Nov 27;11(1):6078 [PMID: 33247138]
  31. Nat Rev Immunol. 2020 Jun;20(6):355-362 [PMID: 32376901]
  32. Virology. 2021 Feb;554:97-105 [PMID: 33412411]
  33. J Immunol. 2010 Feb 1;184(3):1168-79 [PMID: 20042593]
  34. J Virol. 2007 Feb;81(4):2025-30 [PMID: 17151098]
  35. Bioinformatics. 2013 Jan 1;29(1):15-21 [PMID: 23104886]
  36. Curr Opin Virol. 2011 Dec;1(6):476-86 [PMID: 22323926]
  37. Lancet Infect Dis. 2020 May;20(5):565-574 [PMID: 32213337]
  38. BMC Bioinformatics. 2008 Dec 29;9:559 [PMID: 19114008]
  39. Cell. 2020 Sep 17;182(6):1419-1440.e23 [PMID: 32810438]
  40. Science. 2020 Aug 14;369(6505):806-811 [PMID: 32434945]
  41. Curr Opin Virol. 2015 Aug;13:123-9 [PMID: 26184451]
  42. Cell. 2020 May 28;181(5):1036-1045.e9 [PMID: 32416070]
  43. Nature. 2005 Apr 7;434(7034):772-7 [PMID: 15800576]
  44. PLoS One. 2016 May 12;11(5):e0155484 [PMID: 27171557]
  45. Science. 2020 Sep 4;369(6508):1210-1220 [PMID: 32788292]
  46. Blood. 2008 Oct 15;112(8):3444-54 [PMID: 18669870]
  47. Nat Med. 2004 Mar;10(3):290-3 [PMID: 14981511]
  48. Science. 2020 Aug 7;369(6504):718-724 [PMID: 32661059]
  49. J Immunol. 2007 Mar 15;178(6):3368-72 [PMID: 17339430]
  50. Int J Lab Hematol. 2021 Apr;43(2):324-328 [PMID: 33010111]
  51. J Exp Med. 2020 Jun 1;217(6): [PMID: 32302401]

Grants

  1. P51 OD011104/NIH HHS
  2. R21 OD031229/NIH HHS

MeSH Term

Animals
COVID-19
Cell Degranulation
Chlorocebus aethiops
Disease Models, Animal
Macaca mulatta
Neutrophils
SARS-CoV-2
Species Specificity