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Journal for Veterinary Medicine, Biotechnology and Biosafety

Volume 11, Issue 1, January 2025, Pages 16–21

ISSN 2411-3174 (print version) ISSN 2411-0388 (online version)

IDENTIFICATION OF CONSERVED THREE-WAY JUNCTION IN THE GENOME OF THE BOVINE FOAMY VIRUS

Balak O. K. ¹, Limanskaya O. Yu. ²

¹ Kharkiv National Medical University, Kharkiv, Ukraine

² National Scientific Center ‘Institute of Experimental and Clinical Veterinary Medicine’, Kharkiv, Ukraine, e-mail: olgaliman@ukr.net

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Citation for print version: Balak, O. K. and Limanskaya, O. Yu. (2025) ‘Identification of conserved three-way junction in the genome of the bovine foamy virus’, Journal for Veterinary Medicine, Biotechnology and Biosafety, 11(1), pp. 16–21.

Download PDF (online version)

Citation for online version: Balak, O. K. and Limanskaya, O. Yu. (2025) ‘Identification of conserved three-way junction in the genome of the bovine foamy virus’, Journal for Veterinary Medicine, Biotechnology and Biosafety, 11(1), pp. 16–21. DOI: 10.36016/JVMBBS-2025-11-1-3.

Summary. Three-way junctions (3WJs) belong to unusual structures in DNA and RNA. 3WJs are non-canonical structures like G-quadruplexes, triplexes (H-DNA), cruciform, hairpin structures, A-DNA, and Z-DNA that differ from the classic double-stranded B-DNA. 3WJs play an important role in many biological processes and may be associated with some human diseases. This study aimed to search for putative 3WJ structures in the mRNA of bovine foamy virus (BFV). Bioinformatic analysis was used to analyze conserved RNA structural motifs of intramolecular 3WJ in BFV mRNA. The Vfold2D software was used to search for structural motifs in the 3WJ RNA. Multiple sequence alignment was conducted using MEGA software. For the confirmation of secondary structures and the determination of the thermodynamic parameters of 3WJs, Mfold software from the UNAFold web server was utilized. Based on multiple alignments of 37 BFV isolates with the complete genome, we found 6 putative 3WJ structures in the BFV mRNA, which are stabilized by 20–26 complementary nucleotides pairs (ntp) and localized in the gag, env, bel2 genes, as well as in the 5’LTR. However, only two 3WJ structures in gag and env genes from the abovementioned six ones, designed by the Mfold software, coincide with 3WJ structures determined by the Vfold2D software. Five 3WJ structures from 6 identified ones are not conserved. Conserved 3WJ structure with a length of 73 nt for a set of 37 BFV isolates with complete genome is localized between 5’-LTR and 5’-end of gag gene and partially covers 5’-end of gag gene. This intramolecular secondary structure is formed by three duplexes and stabilized by 20 complementary ntp with a free energy of −19.8 kcal/mol. Our analysis of SNPs in the paper (Bao et al., 2020), which arose after serial passages of BFV Riems-infected MDBK cells has shown that the determined 3WJ structure is retained, indicating the importance of this alternative structure for BFV functioning

Keywords: bovine foamy virus, three-way junction, 3WJ, structural motif

References:

Assenberg, R., Weston, A., Cardy, D. L. N., and Fox, K. R. (2002) ‘Sequence-dependent folding of DNA three-way junctions’, Nucleic Acids Research, 30(23), pp. 5142–5150. doi: 10.1093/nar/gkf637.

Bailey, S., Wichitwechkarn, J., Johnson, D., Reilly, B. E., Anderson, D. L. and Bodley, J. W. (1990) ‘Phylogenetic analysis and secondary structure of the Bacillus subtilis bacteriophage RNA required for DNA packaging’, Journal of Biological Chemistry, 265(36), pp. 22365–22370. doi: 10.1016/S0021-9258(18)45714-6.

Bajaj, P., Steger, G. and Hammann, C. (2011) ‘Sequence elements outside the catalytic core of natural hairpin ribozymes modulate the reactions differentially’, Biological Chemistry, 392(7), pp. 593–600. doi: 10.1515/bc.2011.071.

Bao, Q., Hotz-Wagenblatt, A., Betts, M. J., Hipp, M., Hugo, A., Pougialis, G., Lei-Rossmann, J. and Löchelt, M. (2020) ‘Shared and cell type-specific adaptation strategies of Gag and Env yield high titer bovine foamy virus variants’, Infection, Genetics and Evolution, 82, p. 104287. doi: 10.1016/j.meegid.2020.104287.

Chen, K., Eargle, J., Lai, J., Kim, H., Abeysirigunawardena, S., Mayerle, M., Woodson, S., Ha, T. and Luthey-Schulten, Z. (2012) ‘Assembly of the five-way junction in the ribosomal small subunit using hybrid MD-Go̅ simulations’, The Journal of Physical Chemistry B, 116(23), pp. 6819–6831. doi: 10.1021/jp212614b.

Chu, C.-C., Plangger, R., Kreutz, C. and Al-Hashimi, H. M. (2019) ‘Dynamic ensemble of HIV-1 RRE stem IIB reveals non-native conformations that disrupt the Rev-binding site’, Nucleic Acids Research, 47(13), pp. 7105–7117. doi: 10.1093/nar/gkz498.

Foguel, M. V., Zamora, V., Ojeda, J., Reed, M., Bennett, A., Calvo-Marzal, P., Gerasimova, Y. V., Kolpashchikov, D. and Chumbimuni-Torres, K. Y. (2024) ‘DNA nanotechnology for nucleic acid analysis: sensing of nucleic acids with DNA junction-probes’, The Analyst, 149(3), pp. 968–974. doi: 10.1039/D3AN01707A.

Guo, P., Erickson, S. and Anderson, D. (1987) ‘A small viral RNA is required for in vitro packaging of bacteriophage φ29 DNA’, Science, 236(4802), pp. 690–694. doi: 10.1126/science.3107124.

Hechler, T., Materniak, M., Kehl, T., Kuzmak, J. and Löchelt, M. (2012) ‘Complete genome sequences of two novel European clade bovine foamy viruses from Germany and Poland’, Journal of Virology, 86(19), pp. 10905–10906. doi: 10.1128/JVI.01875-12.

Hill, A. C. and Schroeder, S. J. (2017) ‘Thermodynamic stabilities of three-way junction nanomotifs in prohead RNA’, RNA, 23(4), pp. 521–529. doi: 10.1261/rna.059220.116.

Kadrmas, J. L., Ravin, A. J. and Leontis, N. B. (1995) ‘Relative stabilities of DNA three-way, four-way and five-way junctions (multi-helix junction loops): Unpaired nucleotides can be stabilizing or destabilizing’, Nucleic Acids Research, 23(12), pp. 2212–2222. doi: 10.1093/nar/23.12.2212.

Kashefi-Kheyrabadi, L., Nguyen, H. V., Go, A., Baek, C., Jang, N., Lee, J. M., Cho, N.-H., Min, J. and Lee, M.-H. (2022) ‘Rapid, multiplexed, and nucleic acid amplification-free detection of SARS-CoV-2 RNA using an electrochemical biosensor’, Biosensors and Bioelectronics, 195, p. 113649. doi: 10.1016/j.bios.2021.113649.

Khan, A. S., Bodem, J., Buseyne, F., Gessain, A., Johnson, W., Kuhn, J. H., Kuzmak, J., Lindemann, D., Linial, M. L., Löchelt, M., Materniak-Kornas, M., Soares, M. A. and Switzer, W. M. (2018) ‘Spumaretroviruses: Updated taxonomy and nomenclature’, Virology, 516, pp. 158–164. doi: 10.1016/j.virol.2017.12.035.

Koirala, D., Shao, Y., Koldobskaya, Y., Fuller, J. R., Watkins, A. M., Shelke, S. A., Pilipenko, E. V., Das, R., Rice, P. A. and Piccirilli, J. A. (2019) ‘A conserved RNA structural motif for organizing topology within picornaviral internal ribosome entry sites’, Nature Communications, 10(1), p. 3629. doi: 10.1038/s41467-019-11585-z.

Lindemann, D., Hütter, S., Wei, G. and Löchelt, M. (2021) ‘The unique, the known, and the unknown of spumaretrovirus assembly’, Viruses, 13(1), p. 105. doi: 10.3390/v13010105.

Luo, X., McKeague, M., Pitre, S., Dumontier, M., Green, J., Golshani, A., Derosa, M. C. and Dehne, F. (2010) ‘Computational approaches toward the design of pools for the in vitro selection of complex aptamers’, RNA, 16(11), pp. 2252–2262. doi: 10.1261/rna.2102210.

Lynch, C. A., Foguel, M. V., Reed, A. J., Balcarcel, A. M., Calvo-Marzal, P., Gerasimova, Y. V. and Chumbimuni-Torres, K. Y. (2019) ‘Selective determination of isothermally amplified Zika virus RNA using a universal DNA-hairpin probe in less than 1 hour’, Analytical Chemistry, 91(21), pp. 13458–13464. doi: 10.1021/acs.analchem.9b02455.

Mathews, D. H., Disney, M. D., Childs, J. L., Schroeder, S. J., Zuker, M. and Turner, D. H. (2004) ‘Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure’, Proceedings of the National Academy of Sciences, 101(19), pp. 7287–7292. doi: 10.1073/pnas.0401799101.

McGorman, B., Poole, S., López, M. V. and Kellett, A. (2023) ‘Analysis of non-canonical three- and four-way DNA junctions’, Methods, 219, pp. 30–38. doi: 10.1016/j.ymeth.2023.09.002.

Melcher, S. E., Wilson, T. J. and Lilley, D. M. J. (2003) ‘The dynamic nature of the four-way junction of the hepatitis C virus IRES’, RNA, 9(7), pp. 809–820. doi: 10.1261/rna.5130703.

Ojeda, J., Torres-Salvador, F., Bruno, N., Eastwood, H., Gerasimova, Y. and Chumbimuni-Torres, K. (2024) ‘Highly reproducible electrochemical biosensor for Influenza A virus towards low-resource settings’, Analytical Methods, 16(5), pp. 772–779. doi: 10.1039/D3AY01825C.

Ojha, M., Vogt, J., Das, N. K., Redmond, E., Singh, K., Banna, H. A., Sadat, T. and Koirala, D. (2024) ‘Structure of saguaro cactus virus 3′ translational enhancer mimics 5′ cap for eIF4E binding’, Proceedings of the National Academy of Sciences, 121(4), p. e2313677121. doi: 10.1073/pnas.2313677121.

Ouellet, J., Melcher, S., Iqbal, A., Ding, Y. and Lilley, D. M. J. (2010) ‘Structure of the three-way helical junction of the hepatitis C virus IRES element’, RNA, 16(8), pp. 1597–1609. doi: 10.1261/rna.2158410.

Serganov, A., Huang, L. and Patel, D. J. (2008) ‘Structural insights into amino acid binding and gene control by a lysine riboswitch’, Nature, 455(7217), pp. 1263–1267. doi: 10.1038/nature07326.

Shu, D., Shu, Y., Haque, F., Abdelmawla, S. and Guo, P. (2011) ‘Thermodynamically stable RNA three-way junction for constructing multifunctional nanoparticles for delivery of therapeutics’, Nature Nanotechnology, 6(10), pp. 658–667. doi: 10.1038/nnano.2011.105.

Song, Z., Gremminger, T., Singh, G., Cheng, Y., Li, J., Qiu, L., Ji, J., Lange, M. J., Zuo, X., Chen, S.-J., Zou, X., Boris-Lawrie, K. and Heng, X. (2021) ‘The three-way junction structure of the HIV-1 PBS-segment binds host enzyme important for viral infectivity’, Nucleic Acids Research, 49(10), pp. 5925–5942. doi: 10.1093/nar/gkab342.

Song, Q., Hu, Y., Yin, A., Wang, H. and Yin, Q. (2022) ‘DNA holliday junction: History, regulation and bioactivity’, International Journal of Molecular Sciences, 23(17), p. 9730. doi: 10.3390/ijms23179730.

Tamura, K., Stecher, G., Peterson, D., Filipski, A. and Kumar, S. (2013) ‘MEGA6: Molecular Evolutionary Genetics Analysis version 6.0’, Molecular Biology and Evolution, 30(12), pp. 2725–2729. doi: 10.1093/molbev/mst197.

Wu, B., Girard, F., van Buuren, B., Schleucher, J., Tessari, M. and Wijmenga, S. (2004) ‘Global structure of a DNA three-way junction by solution NMR: towards prediction of 3H fold’, Nucleic Acids Research, 32(10), pp. 3228–3239. doi: 10.1093/nar/gkh645.

Xue, Y., Gracia, B., Herschlag, D., Russell, R. and Al-Hashimi, H. M. (2016) ‘Visualizing the formation of an RNA folding intermediate through a fast highly modular secondary structure switch’, Nature Communications, 7(1), p. ncomms11768. doi: 10.1038/ncomms11768.

Yamabe, M., Kaihatsu, K. and Ebara, Y. (2018) ‘Sialyllactose-modified three-way junction DNA as binding inhibitor of influenza virus hemagglutinin’, Bioconjugate Chemistry, 29(5), pp. 1490–1494. doi: 10.1021/acs.bioconjchem.8b00045.

Zhang, H., Endrizzi, J. A., Shu, Y., Haque, F., Sauter, C., Shlyakhtenko, L. S., Lyubchenko, Y., Guo, P. and Chi, Y.-I. (2013) ‘Crystal structure of 3WJ core revealing divalent ion-promoted thermostability and assembly of the Phi29 hexameric motor pRNA’, RNA, 19(9), pp. 1226–1237. doi: 10.1261/rna.037077.112.

Zuker, M. (2003) ‘Mfold web server for nucleic acid folding and hybridization prediction’, Nucleic Acids Research, 31(13), pp. 3406–3415. doi: 10.1093/nar/gkg595.