Transcriptional Differential Analysis of Nitazoxanide-Mediated Anticanine Parvovirus Effect in F81 Cells.

Xia Su, Hongzhuan Zhou, Ziwei Han, Fuzhou Xu, Bing Xiao, Jin Zhang, Qi Qi, Lulu Lin, Huanhuan Zhang, Songping Li, Bing Yang
Author Information
  1. Xia Su: Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China.
  2. Hongzhuan Zhou: Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China.
  3. Ziwei Han: Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China.
  4. Fuzhou Xu: Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China.
  5. Bing Xiao: Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China.
  6. Jin Zhang: Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China.
  7. Qi Qi: Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China.
  8. Lulu Lin: Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China.
  9. Huanhuan Zhang: Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China.
  10. Songping Li: Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China.
  11. Bing Yang: Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China.

Abstract

Canine parvovirus (CPV) is a single-stranded DNA virus that can cause typical hemorrhagic enteritis, and it is one of the common canine lethal viruses. In previous studies, we screened the Food and Drug Administration (FDA)'s drug library and identified nitazoxanide (NTZ), which has anti-CPV capabilities. To investigate the potential antiviral mechanisms, we first reconfirmed the inhibitory effect of NTZ on the CPV by inoculating with different doses and treating for different lengths of time. Then, the differences in the transcription levels between the 0.1%-DMSO-treated virus group and the NTZ-treated virus group were detected using RNA-seq, and a total of 758 differential expression genes (DEGs) were finally identified. Further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the DEGs revealed that these genes are involved in a variety of biological processes and/or signaling pathways, such as cell cycle, mitosis and cell proliferation and differentiation. A protein-protein interaction (PPI) analysis further identified hub genes associated with cell cycle and division among the DEGs. In addition, the expression levels of some of the enriched genes were detected, which were consistent with the high-throughput sequencing results. Moreover, when the cell cycle was regulated with cell cycle checkpoint kinase 1 (Chk1) inhibitor MK-8776 or Prexasertib HCl, both inhibitors inhibited the CPV. In summary, the transcriptome differential analysis results presented in this paper lay the foundation for further research on the molecular mechanism and potential targets of NTZ anti-CPV.

Keywords

References

  1. Vet Microbiol. 2020 Aug;247:108760 [PMID: 32768213]
  2. PeerJ. 2020 Sep 29;8:e9869 [PMID: 33062416]
  3. ACS Infect Dis. 2021 Jun 11;7(6):1317-1331 [PMID: 33352056]
  4. Arch Virol. 2015 Nov;160(11):2799-805 [PMID: 26315688]
  5. Antimicrob Agents Chemother. 2015 Feb;59(2):1061-9 [PMID: 25451059]
  6. Infect Dis Rep. 2021 Jul 14;13(3):636-644 [PMID: 34287319]
  7. Future Virol. 2010 Nov;5(6):731-743 [PMID: 21331319]
  8. Viruses. 2021 Oct 09;13(10): [PMID: 34696470]
  9. Mol Neurobiol. 2023 Nov;60(11):6227-6247 [PMID: 37439957]
  10. Transbound Emerg Dis. 2016 Apr;63(2):e262-9 [PMID: 25209922]
  11. J Virol. 2019 Dec 12;94(1): [PMID: 31619551]
  12. Antiviral Res. 2014 Oct;110:94-103 [PMID: 25108173]
  13. Vet Microbiol. 2002 Oct 22;89(2-3):115-27 [PMID: 12243889]
  14. Viruses. 2019 Aug 13;11(8): [PMID: 31412574]
  15. Cell Mol Life Sci. 2022 Apr 7;79(5):227 [PMID: 35391601]
  16. Transbound Emerg Dis. 2020 May;67(3):1074-1081 [PMID: 31886933]
  17. Virus Genes. 2016 Jun;52(3):411-6 [PMID: 27038801]
  18. J Virol. 2010 Jun;84(12):5909-22 [PMID: 20375165]
  19. Sci Rep. 2016 Jun 02;6:27148 [PMID: 27250526]
  20. Cell Growth Differ. 1995 Jul;6(7):781-7 [PMID: 7547499]
  21. Int J Biol Macromol. 2017 Jun;99:511-518 [PMID: 28238913]
  22. Vet Clin North Am Small Anim Pract. 1993 May;23(3):555-68 [PMID: 8389070]
  23. Mol Biol Rep. 2022 Nov;49(11):11169-11176 [PMID: 36094778]
  24. Front Microbiol. 2022 Feb 28;13:862352 [PMID: 35295295]
  25. iScience. 2019 Sep 27;19:1279-1290 [PMID: 31402258]
  26. J Virol. 2001 Nov;75(22):11071-8 [PMID: 11602746]
  27. Front Vet Sci. 2020 Feb 20;7:5 [PMID: 32154272]
  28. J Virol. 2012 Aug;86(15):8328-32 [PMID: 22623787]
  29. Antiviral Res. 2008 Jan;77(1):56-63 [PMID: 17888524]
  30. Future Microbiol. 2008 Oct;3(5):539-45 [PMID: 18811238]
  31. Baillieres Clin Haematol. 1995 Mar;8(1):57-71 [PMID: 7663051]
  32. Vet Microbiol. 2012 Feb 24;155(1):1-12 [PMID: 21962408]
  33. Gene. 2022 May 15;822:146324 [PMID: 35182681]
  34. Virus Genes. 2016 Dec;52(6):768-779 [PMID: 27339228]
  35. Curr Drug Discov Technol. 2018;15(3):201-213 [PMID: 28748751]
  36. Int J Nanomedicine. 2010 Aug 09;5:417-28 [PMID: 20957163]
  37. Cell Chem Biol. 2016 Mar 17;23(3):340-51 [PMID: 26877023]
  38. J Vet Med B Infect Dis Vet Public Health. 2005 Sep-Oct;52(7-8):303-11 [PMID: 16316389]

Grants

  1. PT2023-4/Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry
  2. KJCX20220422/Innovative Capability Project of Beijing Academy of Agriculture and Forestry Sciences
  3. XMS202317/Reform and Development Project of Beijing Academy of Agricultural and Forestry Sciences
  4. XLYC1902048/Liao Ning Revitalization Talents Program
  5. KJCX20230213/Innovative Capability Project of Beijing Academy of Agriculture and Forestry Sciences

MeSH Term

Animals
Dogs
Gene Expression Profiling
Nitro Compounds
Thiazoles
Parvoviridae Infections
Parvovirus, Canine
Computational Biology
Transcriptome

Chemicals

nitazoxanide
Nitro Compounds
Thiazoles

Word Cloud

Created with Highcharts 10.0.0cellcyclegenesCPVvirusidentifiedNTZDEGsparvoviruscaninenitazoxanideanti-CPVpotentialdifferentlevelsgroupdetectedRNA-seqdifferentialexpressionanalysisresultsCaninesingle-strandedDNAcancausetypicalhemorrhagicenteritisonecommonlethalvirusespreviousstudiesscreenedFoodDrugAdministrationFDA'sdruglibrarycapabilitiesinvestigateantiviralmechanismsfirstreconfirmedinhibitoryeffectinoculatingdosestreatinglengthstimedifferencestranscription01%-DMSO-treatedNTZ-treatedusingtotal758finallyGeneOntologyGOKyotoEncyclopediaGenesGenomesKEGGenrichmentanalysesrevealedinvolvedvarietybiologicalprocessesand/orsignalingpathwaysmitosisproliferationdifferentiationprotein-proteininteractionPPIhubassociateddivisionamongadditionenrichedconsistenthigh-throughputsequencingMoreoverregulatedcheckpointkinase1Chk1inhibitorMK-8776PrexasertibHClinhibitorsinhibitedsummarytranscriptomepresentedpaperlayfoundationresearchmolecularmechanismtargetsTranscriptionalDifferentialAnalysisNitazoxanide-MediatedAnticanineParvovirusEffectF81Cells

Similar Articles

Cited By