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Virus research2010; 149(1); 124-127; doi: 10.1016/j.virusres.2010.01.008

Bovine papillomavirus type 1 E2 and E7 proteins down-regulate Toll Like Receptor 4 (TLR4) expression in equine fibroblasts.

Abstract: BPV-1 and less commonly BPV-2 are associated with the pathogenesis of equine skin tumours termed sarcoids. We recently documented the transcriptional changes that are induced by BPV-1 in equine fibroblasts using microarray analyses. TLR4 expression was found to be significantly down-regulated by BPV-1. In the present study, we show that TLR4 expression is significantly decreased following the exogenous expression of BPV-1 E2 and E7 in primary equine fibroblasts. The results were confirmed by the demonstration of increased TLR4 expression following siRNA suppression of BPV-1 E2 and E7 viral gene expression. These data imply that BPV-1 is able to subvert the innate immune response by downregulation of TLR4.
Publication Date: 2010-01-28 PubMed ID: 20109504DOI: 10.1016/j.virusres.2010.01.008Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research paper investigates how Bovine papillomavirus type 1 (BPV-1), a virus implicated in the formation of skin tumors in horses, suppresses the immune response by reducing the expression of Toll Like Receptor 4 (TLR4) in horse fibroblast cells.

Research Background and Methods

  • The study expands on previous research where the authors identified changes in gene expression in horse fibroblasts induced by BPV-1 using microarray analysis, a technique that allows for the simultaneous examination of thousands of genes.
  • The central focus of this research is on the expression of the Toll Like Receptor 4 (TLR4), a type of protein that play a crucial role in the immune system by helping recognize and respond to pathogens. Specifically, the researchers observed that BPV-1 significantly reduces the expression of TLR4.

Findings and Results

  • Through further experiments, the researchers confirmed their observation: the introduction of BPV-1 E2 and E7 proteins in primary horse fibroblasts significantly reduced TLR4 expression.
  • This finding was validated by another experiment where they increased TLR4 expression by suppressing the effects E2 and E7 proteins—specific genes of BPV-1—using small interfering RNAs (siRNAs), molecules that can interfere with the expression of specific genes.

Implications and Conclusion

  • The research makes an important contribution to understanding the relationship between BPV-1 and the host’s immune response. The data suggests that the virus employs a strategy to evade the host’s immune system by downregulating TLR4, which could help the virus persist and cause skin tumors in horses.
  • These findings could open up potential avenues for the development of new intervention strategies targeting the effects of BPV-1 on TLR4 to manage or prevent the development of skin tumours in horses.

Cite This Article

APA
Yuan ZQ, Bennett L, Campo MS, Nasir L. (2010). Bovine papillomavirus type 1 E2 and E7 proteins down-regulate Toll Like Receptor 4 (TLR4) expression in equine fibroblasts. Virus Res, 149(1), 124-127. https://doi.org/10.1016/j.virusres.2010.01.008

Publication

ISSN: 1872-7492
NlmUniqueID: 8410979
Country: Netherlands
Language: English
Volume: 149
Issue: 1
Pages: 124-127

Researcher Affiliations

Yuan, Z Q
  • Division of Pathological Sciences, Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow, Bearsden Road, Garscube Campus, Glasgow, Scotland G61 1QH, UK.
Bennett, L
    Campo, M S
      Nasir, L

        MeSH Terms

        • Animals
        • Bovine papillomavirus 1 / immunology
        • Bovine papillomavirus 1 / pathogenicity
        • Cells, Cultured
        • DNA-Binding Proteins / antagonists & inhibitors
        • DNA-Binding Proteins / immunology
        • Down-Regulation
        • Equidae
        • Fibroblasts / virology
        • Gene Silencing
        • Host-Pathogen Interactions
        • Oncogene Proteins, Viral / antagonists & inhibitors
        • Oncogene Proteins, Viral / immunology
        • RNA, Small Interfering / genetics
        • Toll-Like Receptor 4 / biosynthesis
        • Viral Proteins / antagonists & inhibitors
        • Viral Proteins / immunology

        Grant Funding

        • Cancer Research UK

        Citations

        This article has been cited 8 times.
        1. Jindra C, Hainisch EK, Brandt S. Immunotherapy of Equine Sarcoids-From Early Approaches to Innovative Vaccines.. Vaccines (Basel) 2023 Mar 30;11(4).
          doi: 10.3390/vaccines11040769pubmed: 37112681google scholar: lookup
        2. García Coronado PL, Romo Sáenz CI, Kawas JR, Zarate Triviño DG, Ramos Zayas Y, Elena Santana Krímskaya S, Rodríguez Padilla C, Armides Franco Molina M. Design, Synthesis, and Evaluation of Peptides Derived from L1 Protein Against Bovine Papillomavirus-1/2 Identified Along Mexico's Cattle Export Route.. J Vet Res 2023 Mar;67(1):11-21.
          doi: 10.2478/jvetres-2023-0003pubmed: 37008764google scholar: lookup
        3. Hainisch EK, Jindra C, Reicher P, Miglinci L, Brodesser DM, Brandt S. Bovine Papillomavirus Type 1 or 2 Virion-Infected Primary Fibroblasts Constitute a Near-Natural Equine Sarcoid Model.. Viruses 2022 Nov 28;14(12).
          doi: 10.3390/v14122658pubmed: 36560661google scholar: lookup
        4. Wilson AD, Hicks C. Both tumour cells and infiltrating T-cells in equine sarcoids express FOXP3 associated with an immune-supressed cytokine microenvironment.. Vet Res 2016 May 9;47(1):55.
          doi: 10.1186/s13567-016-0339-8pubmed: 27160146google scholar: lookup
        5. Mosseri S, Hetzel U, Hahn S, Michaloupoulou E, Sallabank HC, Knottenbelt DC, Kipar A. Equine sarcoid: In situ demonstration of matrix metalloproteinase expression.. Vet J 2014 Nov;202(2):279-85.
          doi: 10.1016/j.tvjl.2014.07.026pubmed: 25439440google scholar: lookup
        6. Finlay M, Yuan Z, Morgan IM, Campo MS, Nasir L. Equine sarcoids: Bovine Papillomavirus type 1 transformed fibroblasts are sensitive to cisplatin and UVB induced apoptosis and show aberrant expression of p53.. Vet Res 2012 Dec 4;43(1):81.
          doi: 10.1186/1297-9716-43-81pubmed: 23210796google scholar: lookup
        7. Dwivedy A, Aich P. Importance of innate mucosal immunity and the promises it holds.. Int J Gen Med 2011 Apr 12;4:299-311.
          doi: 10.2147/IJGM.S17525pubmed: 21556316google scholar: lookup
        8. Brosnahan MM, Brooks SA, Antczak DF. Equine clinical genomics: A clinician's primer.. Equine Vet J 2010 Oct;42(7):658-70.