Increased Presence of Circulating Cell-Free, Fragmented, Host DNA in Pigs Infected with Virulent African Swine Fever Virus.

Ann Sofie Olesen, Louise Lohse, Camille Melissa Johnston, Thomas Bruun Rasmussen, Anette Bøtner, Graham J Belsham
Author Information
  1. Ann Sofie Olesen: Section for Veterinary Virology, Department of Virus & Microbiological Special Diagnostics, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen, Denmark. ORCID
  2. Louise Lohse: Section for Veterinary Virology, Department of Virus & Microbiological Special Diagnostics, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen, Denmark. ORCID
  3. Camille Melissa Johnston: Section for Veterinary Virology, Department of Virus & Microbiological Special Diagnostics, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen, Denmark. ORCID
  4. Thomas Bruun Rasmussen: Section for Veterinary Virology, Department of Virus & Microbiological Special Diagnostics, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen, Denmark. ORCID
  5. Anette Bøtner: Section for Veterinary Clinical Microbiology, Department of Veterinary and Animal Sciences, University of Copenhagen, Stigbøjlen 4, DK-1870 Frederiksberg, Denmark. ORCID
  6. Graham J Belsham: Section for Veterinary Clinical Microbiology, Department of Veterinary and Animal Sciences, University of Copenhagen, Stigbøjlen 4, DK-1870 Frederiksberg, Denmark. ORCID

Abstract

African swine fever virus (ASFV) causes severe hemorrhagic disease in domestic pigs and wild boar, often with high case fatality rates. The virus replicates in the circulating cells of the monocyte-macrophage lineage and within lymphoid tissues. The infection leads to high fever and a variety of clinical signs. In this study, it was observed that ASFV infection in pigs resulted in a >1000-fold increase in the level of circulating cell-free DNA (cfDNA), derived from the nuclei of host cells in the serum. This change occurred in parallel with the increase in circulating ASFV DNA. In addition, elevated levels (about 30-fold higher) of host mitochondrial DNA (mtDNA) were detected in the serum from ASFV-infected pigs. For comparison, the release of the cellular enzyme, lactate dehydrogenase (LDH), a commonly used marker of cellular damage, was also found to be elevated during ASFV infection, but later and less consistently. The sera from pigs infected with classical swine fever virus (CSFV), which causes a clinically similar disease to ASFV, were also tested but, surprisingly, this infection did not result in the release of cfDNA, mtDNA, or LDH. It was concluded that the level of cfDNA in the serum is a sensitive host marker of virulent ASFV infection.

Keywords

References

  1. Biochim Biophys Acta. 2012 Sep-Oct;1819(9-10):914-20 [PMID: 22142616]
  2. PeerJ. 2023 Sep 18;11:e16072 [PMID: 37744227]
  3. Virus Res. 1997 Jan;47(1):31-40 [PMID: 9037734]
  4. J Gen Virol. 1996 Sep;77 ( Pt 9):2209-19 [PMID: 8811021]
  5. Transbound Emerg Dis. 2021 Sep;68(5):2722-2732 [PMID: 33599077]
  6. Front Microbiol. 2022 Oct 05;13:1011891 [PMID: 36274746]
  7. J Virol. 2020 Apr 16;94(9): [PMID: 32075923]
  8. Virus Res. 2019 Oct 2;271:197614 [PMID: 30953662]
  9. Annu Rev Anim Biosci. 2020 Feb 15;8:221-246 [PMID: 31743062]
  10. Expert Rev Mol Med. 2018 Jan 18;20:e1 [PMID: 29343314]
  11. Viruses. 2021 Aug 30;13(9): [PMID: 34578300]
  12. J Virol Methods. 2011 Dec;178(1-2):161-70 [PMID: 21946285]
  13. Vet Microbiol. 2012 Oct 12;159(3-4):327-36 [PMID: 22608103]
  14. JCI Insight. 2021 Feb 22;6(4): [PMID: 33444289]
  15. Prev Vet Med. 2020 Aug;181:104556 [PMID: 30482617]
  16. J Gen Virol. 2018 May;99(5):613-614 [PMID: 29565243]
  17. Transbound Emerg Dis. 2017 Feb;64(1):300-304 [PMID: 25808027]
  18. Viruses. 2014 Jul 15;6(7):2723-34 [PMID: 25029493]
  19. Vet Res. 2014 Sep 26;45:93 [PMID: 25256695]
  20. Viruses. 2022 Sep 29;14(10): [PMID: 36298701]
  21. Front Vet Sci. 2020 May 19;7:282 [PMID: 32509811]
  22. Viruses. 2021 Nov 22;13(11): [PMID: 34835139]
  23. J Virol Methods. 2005 Dec;130(1-2):36-44 [PMID: 16055202]
  24. Arch Virol. 2003 Apr;148(4):693-706 [PMID: 12664294]
  25. Antiviral Res. 2019 May;165:34-41 [PMID: 30836106]
  26. J Immunol Methods. 2018 Dec;463:27-38 [PMID: 30267663]
  27. J Virol. 2022 Oct 26;96(20):e0082822 [PMID: 36197108]
  28. EFSA J. 2023 May 22;21(5):e08016 [PMID: 37223755]
  29. J Mol Diagn. 2022 May;24(5):476-484 [PMID: 35569878]
  30. Vet Microbiol. 2017 Nov;211:92-102 [PMID: 29102127]
  31. Virus Res. 2013 Apr;173(1):122-30 [PMID: 23137735]
  32. Virus Res. 2020 Oct 2;287:198099 [PMID: 32755631]
  33. Pathogens. 2022 Dec 28;12(1): [PMID: 36678395]
  34. PLoS One. 2011;6(10):e25969 [PMID: 22016795]
  35. Vet World. 2016 Dec;9(12):1413-1419 [PMID: 28096614]
  36. Exp Mol Med. 2020 Jan;52(1):1-6 [PMID: 31915368]
  37. J Gen Virol. 1998 Jun;79 ( Pt 6):1427-38 [PMID: 9634085]

MeSH Term

Swine
Animals
African Swine Fever Virus
African Swine Fever
Sus scrofa
DNA, Mitochondrial
Cell-Free Nucleic Acids

Chemicals

DNA, Mitochondrial
Cell-Free Nucleic Acids

Word Cloud

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