Introduction: Numerous mutations in the bovine tumour necrosis factor receptor type two (TNF-RII) gene have been identified, but their biological consequences remain poorly understood. The aim of this study was to determine whether polymorphism in the analysed loci of the bovine TNF-RII gene is linked with the size of cell subpopulations naturally infected with bovine leukaemia virus (BLV) which serve important immune functions in the host. Material and Methods: Samples originated from 78 cows. Polymorphisms in the studied gene were determined by PCR-RFLP and DNA sequencing by capillary electrophoresis. BLV infection was diagnosed by the immunofluorescence (IMF) technique and nested PCR. Cell subpopulations were immunophenotyped with IMF. Results: Similar and non-significant differences in the average percentages of TNFα+, IgM+TNFα+, and CD11b+TNFα+ cells infected with BLV were noted in individuals with various genotypes in the polymorphic sites g.-1646T > G and g.16534T > C of the TNF-RII gene, and significant differences in the percentages of these subpopulations were observed between selected microsatellite genotypes (g.16512CA(n)). Conclusion: STR polymorphism and the number of CA dinucleotide repeats in intron 1 of the TNF-RII gene influence the frequency of TNF+, CD11b+TNF+, and IgM+TNF+ subpopulations naturally infected with BLV. Polymorphism in the gene’s other two sites do not affect the size of these cell subpopulations.
1. Aida Y., Murakami H., Takahashi M., Takeshima S.: Mechanisms of pathogenesis inducted by bovine leukemia virus as a model for human T-cell leukemia virus. Front Microbiol 2013, 4, 1–11.
2. Aspalter R.M., Eibl M.M., Wolf H.M.: Regulation of TCR-mediated T cell activation by TNF-RII. J Leukoc Biol 2003, 74, 572–582.
3. Bagshaw A.T.M.: Functional mechanisms of microsatellite DNA in eukaryotic genomes. Genome Biol Evol 2017, 9, 2428–2443.
4. Bojarojć-Nosowicz B., Kaczmarczyk E., Stachura A., Kubińska M.: Tumor necrosis factor-alpha (TNFα) gene polymorphism and expression of membrane-bound TNFα protein on CD11b+ and IgM+ cells in cows naturally infected with bovine leukemia virus. Pol J Vet Sci 2015, 3, 533–539.
5. Bojarojć-Nosowicz B., Kaczmarczyk E., Jastrzębska A.: Relationship between polymorphism in the tumor necrosis factor-alpha gene and selected indices and cell subpopulations in naturally bovine leukemia virus infected and healthy cows. Vet Med 2018, 63, 101–109.
6. Bouhlal H., Chomont N., Réquena M., Nasreddine N., Saidi H., Legoff J., Kazatchkine M.D., Bélec L., Hocini H.: Opsonization of HIV with complement enhances infection of dendritic cells and viral transfer to CD4 T cells in a CR3 and DC-SIGN-dependent manner. J Immunol 2007, 178, 1086–1095.
7. Brandt B., Hermann S., Straif K., Tidow N., Buerger H., Chang-Claude J.: Modification of breast cancer risk in young women by a polymorphic sequence in the egfr gene. Cancer Res 2004, 64, 7–12.
8. Buehring G.C., Shen H.M., Schwartz D.A., Lawson J.S.: Bovine leukemia virus linked to breast cancer in Australian women and identified before breast cancer development. PLoS One, 2017, e0179367, doi:10.1371/journal.
9. Buerger H., Gebhardt F., Schmidt H., Beckmann A., Hutmacher K., Simon R., Lelle R., Boecker W., Brandt B.: Length and loss of heterozygosity of an intron 1 polymorphic sequence of egfr is related to cytogenetic alterations and epithelial growth factor receptor expression. Cancer Res 2000, 60, 854–857.
10. Buerger H., Packeisen J., Boecker A., Tidow N., Kersting C., Bielawski K., Isola J., Yatabe Y., Nakachi K., Boecker W., Brandt B.: Allelic length of a CA dinucleotide repeat in the egfr gene correlates with the frequency of amplifications of this sequence - first results of an inter-ethnic breast cancer study. J Pathol 2004, 203, 545–550.
11. Chae S.J., Kim H., Jee B.C., Suh C.S., Kim S.H., Kim J.G.: Tumor necrosis factor (TNF)-TNF receptor gene polymorphisms and their serum levels in Korean women with endometriosis. Am J Reprod Immunol 2008, 60, 432–439.
12. Frie M.C., Coussens P.M.: Bovine leukemia virus: a major silent threat to proper immune responses in cattle. Vet Immunol Immunopathol 2015, 15, 103–114.
13. Gatchel J.R., Zoghbi H.Y.: Diseases of unstable repeat expansion: mechanisms and common principles. Nat Rev Genet 2005, 6, 743–755.
14. Gebhardt F., Zӓnker K.S., Brandt B.: Modulation of epidermal growth factor receptor gene transcription by a polymorphic dinucleotide repeat in intron 1. J Biol Chem 1999, 274, 13176–13180.
15. Harhaj E.W., Harhaj N.S.: Mechanisms of persistent NF-kappaB activation by HTLV-I tax. IUBMB Life 2005, 57, 83–91.
16. Herbein G., O’Brien W.A.: Tumor necrosis factor (TNF)-alpha and TNF receptors in viral pathogenesis. Proc Soc Exp Biol Med 2000, 223, 241–257.
17. Ikeda M., Konnai S., Onuma M., Ishiguro N., Goryo M., Okada K.: Immunohistochemical analysis of expression patterns of tumor necrosis factor receptors on lymphoma cells in enzootic bovine leukosis. J Vet Med Sci 2005, 67, 425–432.
18. Kaczmarczyk E., Bojarojć-Nosowicz B., Cybulska O.: Comparative analysis of an ELISA and fluorescent antibody test for the diagnosis of bovine leukaemia virus infection in cattle. Bull Vet Inst Pulawy 2008, 52, 19–22.
19. Khan S.Q., Khan I., Gupta V.: CD11b activity modulates pathogenesis of lupus nephritis. Front Med 2018, doi: 10.3389/fmed.2018.00052.
20. Konnai S., Usui T., Ikeda M., Koharac J., Hiratab T., Okadab K., Ohashia K., Onuma M.: Imbalance of tumor necrosis factor receptors during progression in bovine leukemia virus infection. Virology 2005, 339, 239–248.
21. Markiewicz L., Rułka J., Kamiński S.: Detection of BLV provirus in different cells by nested-PCR. Bull Vet Inst Pulawy 2003, 47, 325-331.
22. Rahman M.M., McFadden G.: Modulation of tumor necrosis factor by microbial pathogens. PLoS Pathog 2006, 2, 66–77.
23. Sahin F., Sladek T.L.: E2F-1 has dual roles depending on the cell cycle. Int J Biol Sci 2010, 6, 116–128.
24. Sankar V.H., Girisha K.M., Gilmour A., Singh V.P., Sinha N., Tewari S., Ramesh V., Mastana S., Agrawal S.: TNFR2 gene polymorphism in coronary artery disease. Indian J Med Sci 2005, 59, 104–108.
25. Sonay T.B., Koletou M., Wagner A.: A survey of tandem repeat instabilities and associated gene expression changes in 35 colorectal cancers. BMC Genomics 2015, 16, 702.
26. Stachura A., Kaczmarczyk E., Bojarojć-Nosowicz B.: Sequence analysis of the regulatory region of the TNF-RII gene in Polish Holstein-Friesian cows. Genet Mol Res 2013, 12, 1028–1034.
27. Stachura A., Brym P., Bojarojć-Nosowicz B., Kaczmarczyk E.: Polymorphism and expression of the tumor necrosis factor receptor II gene in cows infected with the bovine leukemia virus. Pol J Vet Sci 2016, 19, 125–131.
28. Vieira M.L.C., Santini L., Diniz A.L., Munhoz C.F.: Microsatellite markers: what they mean and why they are so useful. Genet Mol Biol 2016, 39, 312–328.
29. Ye J., Coulouris G., Zaretskaya I., Cutcutache I., Rozen S., Madden T.L.: Primer-BLAST: a tool to design target-specific primers for polymerase chain reaction. BMC Bioinformatics 2012, 18, 134.
30. Zhang W., He L., Liu W., Sun Ch., Ratain M.J.: Exploring the relationship between polymorphic (TG/CA)n repeats in intron 1 regions and gene expression. Human Genomics 2009, 3, 236–245.