Václav Brázda1,2, Otília Porubiaková3,4, Alessio Cantara3,5, Natália Bohálová3,5, Jan Coufal3, Martin Bartas6, Miroslav Fojta3, Jean-Louis Mergny7. 1. Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 612 65, Brno, Czech Republic. vaclav@ibp.cz. 2. Faculty of Chemistry, Brno University of Technology, Purkyňova 118, 612 00, Brno, Czech Republic. vaclav@ibp.cz. 3. Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 612 65, Brno, Czech Republic. 4. Faculty of Chemistry, Brno University of Technology, Purkyňova 118, 612 00, Brno, Czech Republic. 5. Department of Experimental Biology, Faculty of Science, Masaryk University, Kamenice 5, 62500, Brno, Czech Republic. 6. Department of Biology and Ecology/Institute of Environmental Technologies, Faculty of Science, University of Ostrava, 710 00, Ostrava, Czech Republic. 7. Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 612 65, Brno, Czech Republic. mergny@ibp.cz.
Abstract
BACKGROUND: Influenza viruses are dangerous pathogens. Seventy-Seven genomes of recently emerged genotype 4 reassortant Eurasian avian-like H1N1 virus (G4-EA-H1N1) are currently available. We investigated the presence and variation of potential G-quadruplex forming sequences (PQS), which can serve as targets for antiviral treatment. RESULTS: PQS were identified in all 77 genomes. The total number of PQS in G4-EA-H1N1 genomes was 571. Interestingly, the number of PQS per genome in individual close relative viruses varied from 4 to 12. PQS were not randomly distributed in the 8 segments of the G4-EA-H1N1 genome, the highest frequency of PQS being found in the NP segment (1.39 per 1000 nt), which is considered a potential target for antiviral therapy. In contrast, no PQS was found in the NS segment. Analyses of variability pointed the importance of some PQS; even if genome variation of influenza virus is extreme, the PQS with the highest G4Hunter score is the most conserved in all tested genomes. G-quadruplex formation in vitro was experimentally confirmed using spectroscopic methods. CONCLUSIONS: The results presented here hint several G-quadruplex-forming sequences in G4-EA-H1N1 genomes, that could provide good therapeutic targets.
BACKGROUND:Influenza viruses are dangerous pathogens. Seventy-Seven genomes of recently emerged genotype 4 reassortant Eurasian avian-like H1N1 virus (G4-EA-H1N1) are currently available. We investigated the presence and variation of potential G-quadruplex forming sequences (PQS), which can serve as targets for antiviral treatment. RESULTS:PQS were identified in all 77 genomes. The total number of PQS in G4-EA-H1N1 genomes was 571. Interestingly, the number of PQS per genome in individual close relative viruses varied from 4 to 12. PQS were not randomly distributed in the 8 segments of the G4-EA-H1N1 genome, the highest frequency of PQS being found in the NP segment (1.39 per 1000 nt), which is considered a potential target for antiviral therapy. In contrast, no PQS was found in the NS segment. Analyses of variability pointed the importance of some PQS; even if genome variation of influenza virus is extreme, the PQS with the highest G4Hunter score is the most conserved in all tested genomes. G-quadruplex formation in vitro was experimentally confirmed using spectroscopic methods. CONCLUSIONS: The results presented here hint several G-quadruplex-forming sequences in G4-EA-H1N1 genomes, that could provide good therapeutic targets.
Authors: Václav Brázda; Jan Kolomazník; Jiří Lýsek; Martin Bartas; Miroslav Fojta; Jiří Šťastný; Jean-Louis Mergny Journal: Bioinformatics Date: 2019-09-15 Impact factor: 6.937