G-quadruplexes in H1N1 influenza genomes

Václav Brázda,Alessio Cantara,Martin Bartas,Jan Coufal,Jean-Louis Mergny,Natália Bohálová,Otília Porubiaková,Miroslav Fojta

doi:10.1186/s12864-021-07377-9

Abstract

BackgroundInfluenza 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.ResultsPQS 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.ConclusionsThe results presented here hint several G-quadruplex-forming sequences in G4-EA-H1N1 genomes, that could provide good therapeutic targets.

Highlights

potential G-quadruplex forming sequences (PQS) frequencies were analyzed according to individual G4-EA-H1N1 strains, and for statistical comparison we have grouped genomes according to regions of origin (10 groups based on [10]) and according to their genomic segments (8 segments)
Using standard default values for the G4Hunter algorithm, 571 PQSs were found among all genomes and all fragments
Mean PQS frequency for the whole set of sequences was 0.56 PQS per 1000 nt and PQSs cover an average of 1.58% of G4-EAH1N1 genomes

Summary

Introduction

Seventy-Seven genomes of recently emerged genotype 4 reassortant Eurasian avian-like H1N1 virus (G4-EA-H1N1) are currently available. Influenza viruses are deadly pathogens for humans, and more generally mammals, as well as avian species. They belong to the Orthomyxoviridae family and are classified into three types termed Influenza A, B and C. Influenza A viruses (IAVs) pose the greatest threat to human and animal health. IAV genome is divided to 8 segments of negative-sense RNA that encodes 11 proteins [1]. HA protein facilitates binding of the virus to host cell receptors and subsequent endosomal fusion [2], and NA protein is

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Conclusion