Document Type : Original Article

Authors

Department of Agricultural Science and Technology, Nanchong Vocational and Technical College, Nanchong, China

Abstract

The jaagsiekte sheep retrovirus (JSRV), belonging to the betaretrovirus genus of the retroviridae family, includes both exogenous and endogenous jaagsiekte sheep retroviruses (exJSRV and enJSRV, respectively). At the proviral genome level, exJSRV and enJSRV strains have a high degree of similarity with their main variation regions being the LTR, gag, and env genes. In this study, for the first time, we investigated and compared the distribution of CpG islands between these enJSRV and exJSRV strains. Specifically, we analyzed a total of 42 full-length JSRV genomic sequences obtained from the GenBank® database to identify CpG islands in the exJSRV and enJSRV genomes using the MethPrimer software. Our results showed that the CpG islands in the two JSRV strains were mainly distributed in the LTR, gag, and env genes. In exJSRVs, 66.66% (6/9), 33.33% (3/9), and 100% (9/9) of the sequences presented at least one CpG island in LTR, gag, env genes, respectively, and for enJSRVs, 84.84% (28/33), 57.57% (19/33), and 96.96% (32/33) of the sequences presented at least one CpG island in the LTR, gag, and env genes. These findings suggested that the distribution, length, and genetic traits of CpG islands were different for the exJSRV and enJSRV strains. In future, it would be necessary to demonstrate the biological significance of CpG islands within these genes in exJSRV and enJSRV genomes. This will enhance understanding regarding the potential role of CpG islands in epigenetic regulation.

Keywords

Main Subjects

  1. Leroux C, Girard N, Cottin V, et al. Jaagsiekte sheep retrovirus (JSRV): from virus to lung cancer in sheep. Vet Res 2007; 38(2): 211-228.
  2. De las Heras M, Ortín A, Cousens C, et al. Enzootic nasal adenocarcinoma of sheep and goats. Curr Top Microbiol Immunol 2003; 275: 201-223.
  3. York DF, Querat G. A history of ovine pulmonary adenocarcinoma (jaagsiekte) and experiments leading to the deduction of the JSRV nucleotide sequence. Curr Top Microbiol Immunol 2003; 275: 1-23.
  4. De Las Heras M, Borobia M, Ortín A. Neoplasia-associated wasting diseases with economic relevance in the sheep industry. Animals (Basel) 2021; 11(2): 381. doi: 10.3390/ani11020381.
  5. Zhang K, Kong H, Liu Y, et al. Diagnosis and phylogenetic analysis of ovine pulmonary adenocarcinoma in China. Virus Genes 2014; 48(1): 64-73.
  6. Shi W, Jia S, Guan X, et al. A survey of jaagsiekte sheep retrovirus (JSRV) infection in sheep in the three northeastern provinces of China. Arch Virol 2021; 166(3): 831-840.
  7. Yang S, Liang T, Zhao Q, et al. Pathological diagnoses and whole-genome sequence analyses of the jaagsiekte sheep retrovirus in Xinjiang, China [Chinese]. Bing Du Xue Bao 2015; 31(3): 217-225.
  8. Chiu ES, VandeWoude S. Endogenous retroviruses drive resistance and promotion of exogenous retroviral homologs. Annu Rev Anim Biosci2021; 9: 225-248.
  9. Youssef G, Wallace WA, Dagleish MP, et al. Ovine pulmonary adenocarcinoma: a large animal model for human lung cancer. ILAR J 2015; 56(1): 99-115.
  10. Gray ME, Meehan J, Sullivan P, et al. Ovine pulmonary adenocarcinoma: a unique model to improve lung cancer research. Front Oncol 2015; 9: 335. doi: 10.3389/fonc.2019.00335
  11. Lanigan LG, Hildreth BE 3rd, Dirksen WP, et al. In vivo tumorigenesis, osteolytic sarcomas, and tumorigenic cell lines from transgenic mice expressing the human t-lymphotropic virus type 1 (HTLV-1) Tax viral oncogene. Am J Pathol 2021; 191(2): 335-352.
  12. Durkin K, Rosewick N, Artesi M, et al. Characterization of novel bovine leukemia virus (BLV) antisense transcripts by deep sequencing reveals constitutive expression in tumors and transcriptional interaction with viral microRNAs. Retrovirology 2016; 13(1): 33. doi: 10.1186/s12977-016-0267-8.
  13. Voisin V, Barat C, Hoang T, et al. Novel insights into the pathogenesis of the Graffi murine leukemia retrovirus. J Virol 2006; 80(8): 4026-4037.
  14. Irby RB, Mao W, Coppola D, et al. Activating SRC mutation in a subset of advanced human colon cancers. Nat Genet 1999; 21(2): 187-190.
  15. Pecenka V, Pajer P, Karafiat V, et al. HRAS, EGFR, MET, and RON genes are recurrently activated by provirus insertion in liver tumors induced by the retrovirus myeloblastosis-associated virus 2. J Virol 2017; 91(20): e00467-17. doi: 10.1128/JVI.00467-17.
  16. Wootton SK, Halbert CL, Miller AD. Sheep retrovirus structural protein induces lung tumours. Nature 2005; 434(7035): 904-907.
  17. Maeda N, Palmarini M, Murgia C, et al. Direct transformation of rodent fibroblasts by jaagsiekte sheep retrovirus DNA. Proc Natl Acad Sci U S A 2001; 98(8): 4449-4454.
  18. Palmarini M, Maeda N, Murgia C, et al. A phosphatidylinositol 3-kinase docking site in the cytoplasmic tail of the jaagsiekte sheep retrovirus transmembrane protein is essential for envelope-induced transformation of NIH 3T3 cells. J Virol 2001; 75(22): 11002-11009.
  19. Rai SK, Duh FM, Vigdorovich V, et al. Candidate tumor suppressor HYAL2 is a glycosylphosphatidylinositol (GPI)-anchored cell-surface receptor for jaagsiekte sheep retrovirus, the envelope protein of which mediates oncogenic transformation. Proc Natl Acad Sci U S A 2001; 98(8): 4443-4448.
  20. Maeda N, Fu W, Ortin A, et al. Roles of the Ras-MEK-mitogen-activated protein kinase and phosphatidylinositol 3-kinase-Akt-mTOR pathways in jaagsiekte sheep retrovirus-induced transformation of rodent fibroblast and epithelial cell lines. J Virol 2005; 79(7): 4440-4450.
  21. Arnaud F, Caporale M, Varela M, et al. A paradigm for virus-host coevolution: sequential counter-adaptations between endogenous and exogenous retroviruses. PLoS Pathog 2007; 3(11): e170. doi: 10.1371/journal. ppat.0030170.
  22. Lavialle C, Cornelis G, Dupressoir A, et al. Paleovirology of 'syncytins', retroviral env genes exapted for a role in placentation. Philos Trans R Soc Lond B Biol Sci 2013; 368(1626): 20120507. doi: 10.1098/rstb.2012.0507.
  23. Spencer TE, Palmarini M. Endogenous retroviruses of sheep: a model system for understanding physiological adaptation to an evolving ruminant genome. J Reprod Dev 2012; 58(1): 33-37.
  24. Xiao J, Liu P, Wang Y, et al. A novel cognition of decitabine: insights into immunomodulation and antiviral effects. Molecules 2022; 27(6):1973. doi: 10.3390/molecules27061973.
  25. Kausar S, Abbas MN, Cui H. A review on the DNA methyltransferase family of insects: Aspect and prospects. Int J Biol Macromol 2021; 186: 289-302.
  26. Cain JA, Montibus B, Oakey RJ. Intragenic CpG islands and their impact on gene regulation. Front Cell Dev Biol 2022; 10: 832348. doi: 10.3389/fcell.2022.832348.
  27. Mittelstaedt NN, Becker AL, de Freitas DN. DNA methylation and immune memory response. Cells 2021; 10(11): 2943. doi: 10.3390/cells10112943.
  28. Mazloumi Z, Farahzadi R, Rafat A, et al. Effect of aberrant DNA methylation on cancer stem cell properties. Exp Mol Pathol 2022; 125: 104757. doi: 10.1016/j.yexmp.2022.104757.
  29. Nishiyama A, Nakanishi M. Navigating the DNA methylation landscape of cancer. Trends Genet 2021; 37(11): 1012-1027.
  30. Palmarini M, Holland MJ, Cousens C, et al. Jaagsiekte retrovirus establishes a disseminated infection of the lymphoid tissues of sheep affected by pulmonary adenomatosis. J Gen Virol 1996; 77 (Pt 12): 2991-2998.
  31. Hofacre A, Fan H. Multiple domains of the jaagsiekte sheep retrovirus envelope protein are required for transformation of rodent fibroblasts. J Virol 2004; 78(19): 10479-10489.
  32. Palmarini M, Hallwirth C, York D, et al. Molecular cloning and functional analysis of three type D endogenous retroviruses of sheep reveal a different cell tropism from that of the highly related exogenous jaagsiekte sheep retrovirus. J Virol 2000; 74(17): 8065-8076.
  33. Hallwirth C, Maeda N, York D, et al. Variable regions 1 and 2 (VR1 and VR2) in JSRV gag are not responsible for the endogenous JSRV particle release defect. Virus Genes 2005; 30(1): 59-68.
  34. Yang T, Liu X, Kumar SK, et al. Decoding DNA methylation in epigenetics of multiple myeloma. Blood Rev 2022; 51: 100872. doi: 10.1016/j.blre.2021.100872.
  35. Shrestha KS, Tuominen MM, Kauppi L. Mlh1 heterozygosity and promoter methylation associates with microsatellite instability in mouse sperm. Mutagenesis 2021; 36(3): 237-244.
  36. Radpour R, Barekati Z, Haghighi MM, et al. Correlation of telomere length shortening with promoter methylation profile of p16/Rb and p53/p21 pathways in breast cancer. Mod Pathol 2010; 23(5): 763-772.
  37. Meng H, Cao Y, Qin J, et al. DNA methylation, its mediators and genome integrity. Int J Biol Sci 2015; 11(5): 604-617.
  38. Chen CL, Rappailles A, Duquenne L, et al. Impact of replication timing on non-CpG and CpG substitution rates in mammalian genomes. Genome Res 2010; 20(4): 447-457.
  39. Boltz VF, Ceriani C, Rausch JW, et al. CpG methylation profiles of HIV-1 Pro-viral DNA in individuals on ART. Viruses 2021; 13(5): 799. doi: 10.3390/v13050799.
  40. Yan H, Zhang D, Liu H, et al. Chromatin modifications and genomic contexts linked to dynamic DNA methylation patterns across human cell types. Sci Rep 2015; 5: 8410. doi: 10.1038/srep08410.
  41. Palmarini M, Datta S, Omid R, et al. The long terminal repeat of jaagsiekte sheep retrovirus is preferentially active in differentiated epithelial cells of the lungs. J Virol 2000; 74(13): 5776-5787.
  42. McGee-Estrada K, Fan H. In vivo and in vitro analysis of factor binding sites in jaagsiekte sheep retrovirus long terminal repeat enhancer sequences: roles of HNF-3, NF-I, and C/EBP for activity in lung epithelial cells. J Virol 2006; 80(1): 332-341.
  43. McGee-Estrada K, Fan H. Comparison of LTR enhancer elements in sheep beta retroviruses: insights into the basis for tissue-specific expression. Virus Genes 2007; 35(2): 303-312.
  44. Hofacre A, Fan H. Jaagsiekte sheep retrovirus biology and oncogenesis. Viruses 2010; 2(12): 2618-2648.
  45. Hull S, Lim J, Hamil A, et al. Analysis of jaagsiekte sheep retrovirus (JSRV) envelope protein domains in transformation. Virus Genes 2012; 45(3): 508-517.
  46. Rosales Gerpe MC, van Lieshout LP, Domm JM, et al. The U3 and Env proteins of jaagsiekte sheep retrovirus and enzootic nasal tumor virus both contribute to tissue tropism. Viruses 2019; 11(11):1061. doi:3390/v11111061.
  47. Chen L, Liu S, Tao Y. Regulating tumor suppressor genes: post-translational modifications. Sig Transduct Target Ther 2020; 5: 90. doi: 10.1038/s41392-020-0196-9
  48. Ehrlich M. DNA hypermethylation in disease: mechanisms and clinical relevance. Epigenetics 2019; 14(12): 1141-1163.